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Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.
The X-ray emissions in the interaction of 3–6 MeV Xe23+ ions into thick solid In target are measured. The projectile-to-target and target Lα/Lβ X-ray production intensity ratios are observed to strongly depend on the projectile energy. The dependence deviates from Coulomb ionization predictions, which implies the important roles of coupling between subshells and the activation of 4fσ rotational couplings for projectile energy larger than 5 MeV.
In recent years, there has been a significant thrust toward the development of novel implant alloys based on β-Ti with low Young’s modulus to prevent stress shielding. In this study, porous Ti–Nb–Ta–Zr alloys with porosity of <55% and macro-pore size of 100–400 μm for biomedical applications were successfully fabricated by a space-holder method. The microstructure and compressive behavior were studied. The results show that the micro-pore size of porous Ti–Nb–Ta–Zr alloys decreases with an increase in the amount of the process control agent (PCA), which has no obvious effect on the porosity and the macro-pore size formed by the space holder. Porous Ti–Nb–Ta–Zr alloys fail mainly because of the cleavage and ductile fracture with some dimples in compression. The compressive modulus increases from 0.6 to 6.5 GPa with the increase in the PCA and decrease of the space holder. The influence mechanism has been analyzed by the finite element calculation and the Gibson–Ashby model.
The modification of halloysite nanotubes (HNTs) as fillers is very effective at improving the performance of polymers. A novel modification of HNTs through grafting dodecylamine onto their surfaces was conducted here. Owing to the improvement in dispersibility of HNTs in polytetrafluoroethylene (PTFE), the mechanical properties and wear resistance (in particular) of the dodecylamine-modified HNT-filled PTFE composite were enhanced significantly.
Objective: Deficits in the semantic learning strategy were observed in subjects with amnestic mild cognitive impairment (aMCI) in our previous study. In the present study, we explored the contributions of executive function and brain structure changes to the decline in the semantic learning strategy in aMCI. Methods: A neuropsychological battery was used to test memory and executive function in 96 aMCI subjects and 90 age- and gender-matched healthy controls (HCs). The semantic clustering ratio on the verbal learning test was calculated to evaluate learning strategy. Medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) were measured on MRI with the MTA and Fazekas visual rating scales, respectively. Results: Compared to HCs, aMCI subjects had poorer performance in terms of memory, executive function, and the semantic clustering ratio (P < .001). In aMCI subjects, no significant correlation between learning strategy and executive function was observed. aMCI subjects with obvious MTA demonstrated a lower semantic clustering ratio than those without MTA (P < .001). There was no significant difference in the learning strategies between subjects with high-grade WMH and subjects with low-grade WMH. Conclusion: aMCI subjects showed obvious impairment in the semantic learning strategy, which was attributable to MTA but independent of executive dysfunction and subcortical WMH. These findings need to be further validated in large cohorts with biomarkers identified using volumetric brain measurements. (JINS, 2019, 25, 706–717)
In order to improve the dispersibility of halloysite nanotubes (HNTs) in polytetrafluoroethylene (PTFE), the modification of HNT surfaces was studied with three types of modifiers (polymethyl methacrylate [PMMA], sodium dodecyl sulfate [SDS] and carboxylic acid). The modified HNTs were characterized by Fourier-transform infrared (FTIR) spectrometry, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and contact angle measurements. The HNTs were used to reinforce the mechanical properties of PTFE. The mechanical results indicated that the tensile strength of the modified HNT-filled PTFE nanocomposites (F-HNT/PTFE) improved to an acceptable degree and Young's modulus increased significantly. The tribological results showed that the wear rate of F-HNT/PTFE decreased by 21–82 and 9–40 times compared to pure PTFE and the pristine F-HNT/PTFE, respectively.
The aim of this study was to investigate the in vivo degradation mechanism and the mechanical properties of poly(lactide-co-glycolide)/beta-tricalcium phosphate (PLGA/β-TCP) composite anchors. Anchors composed of PLGA and β-TCP were implanted in the dorsal subcutaneous tissue of beagle dogs for 6, 12, 16, and 26 weeks. The degradation of the materials was evaluated by measuring the changes in thermal behavior, crystallinity, and mechanical properties. Scanning electron microscope (SEM) was used to observe the surface and longitudinal section of the material. The evaluation of mechanical strength retention and degradation properties suggest that the addition of β-TCP particles efficiently enhances their mechanical properties and thermal characteristics and delays their degradation rate. By analyzing the results of SEM, X-ray diffraction, and differential scanning calorimetry, we can infer that after 12 weeks, the connection between β-TCP and PLGA becomes less compact, which accelerates the decline of mechanical strength.
Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).
Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.
Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).
Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.
Halloysite nanotubes (HNTs)/polytetrafluoroethylene (PTFE) nanocomposites were prepared by the cold compression moulding method. The effects of addition of HNTs (HNTs ‘filling’) on the performances of PTFE were explored using X-ray diffraction, Fourier Transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis which showed that HNTs were well dispersed in the PTFE matrix by means of physical mixing at lower contents of 2–5 wt.%; the introduction of HNTs into PTFE could improve the heat stability of the PTFE. Furthermore, the mechanical and tribological performances of the nanocomposites were measured to examine the filling effect. The tensile strength of the HNTs/PTFE nanocomposites at 2–5 wt.% HNTs content increased by ~3.5% while their wear rates decreased by 55–90% relative to pure PTFE, clear proof of the filling effect of HNTs with a high aspect ratio.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.
The East Asian–Australasian flyway contains some of the most threatened habitats in the world, with at least 155 waterbird species reliant on the tidal habitats it comprises. The black-faced spoonbill (Platalea minor) is an iconic endangered species distributed across the coast of East Asia. Its population suffered a severe decline into the 1990s, but extensive monitoring and conservation interventions have aided a substantial recovery of the species. We used a population viability analysis based on data collected over the past two decades in conjunction with species distribution models to project spatially explicit models of population change for the next 35 years. Over nearly all scenarios of habitat loss and climate change, the global spoonbill population was projected to increase in the short-term due to low population numbers likely well below current population carrying capacities. However, climate change and habitat loss together threaten the recovery of the spoonbill population such that, by 2050, population declines are apparent as a consequence of these cumulative impacts. These threats are also cryptic and represent a challenge to the conservation of species recovering from anthropogenic impacts; observed population increases can hide large reductions in habitat suitability that threaten the long-term viability of species.
Magnetic Fe3O4–polyhedral oligomeric silsesquioxanes (POSS) particles with Si-OH were prepared by hydrosilylation reaction between the Fe3O4–SiH and POSS with hydroxyl and vinyl groups. The magnetic Fe3O4–POSS particles were characterized by using transmission electron microscopy, scanning electron microscopy, Fourier transform infrared absorption spectroscopy, thermogravimetry, and vibrating sample magnetometry. The magnetic saturation value of Fe3O4–POSS particles was 18.77 emu/g. Polyacrylonitrile (PAN)/Fe3O4–POSS nanofibers mats were subsequently fabricated by electrospinning technique. The electret properties of PAN/Fe3O4–POSS nanofibers mats and their aerosol filtration property as electrets filter media were characterized. The stability of the surface potential was remarkably improved and the surface potential retention reached 50% for PAN/Fe3O4–POSS mats with 1 wt% Fe3O4–POSS. Compared with pure PAN, the charge retention of PAN/Fe3O4–POSS was increased by 21% and reached 52.40%. Moreover, the collection efficiency increased and the filter resistance decreased when the PAN nanofibers with Fe3O4–POSS were used as electrets filter media. Our study provided an effective method to prepare novel filter materials with high efficiency and low resistance.
Bulk nanocrystalline (NC) silvers were fabricated by spark plasma sintering process. The effects of sintering temperature on physical and mechanical properties of the NC silvers were investigated. The results indicate that no impurities were introduced into the bulk compacts during the preparation procedure. Both the density and the electrical conductivity of the NC Ag increase with an increase in sintering temperature. However, the micro-hardness and ultimate tensile strength (UTS) of the bulk compacts increase initially and then decrease with increasing sintering temperature. The NC Ag sintered at 500 °C exhibits the highest micro-hardness of 85.3 HV along with the best compression yield strength of 379 MPa and the highest UTS of 534 MPa. The deterioration of the mechanical properties of the NC Ag sintered at 550 °C should be attributed to the rapid grain growth.
Cognition and sleep deficits occur in amnestic mild cognitive impairment (aMCI) and vascular cognitive impairment-no dementia (VCIND). However, how memory and sleep deficits differ between aMCI and VCIND remains unclear.
Fifty aMCI and 50 VCIND patients and 38 sex- and age-matched healthy controls (HCs) were administered the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test-A/B (TMT-A/B), Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Benton Judgment of Line Orientation (JLO) test, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Insomnia Severity Index (ISI) to quantify cognitive deficits and subjective sleep disturbance.
Compared with VCIND patients, aMCI patients had lower HVLT-R scores for total recall (p < 0.001), delayed recall (p < 0.001) and recognition (p = 0.001), and for total-recall (p = 0.002) and delayed-recall (p < 0.001) semantic clustering ratios (SCRs). However, VCIND patients exhibited more obvious executive dysfunction (TMT-A, p < 0.001; TMT-B, p < 0.001; WCST, p < 0.001), lower information processing speed (PASAT, p = 0.003; SDMT, p < 0.001), and more severe sleep disturbance (PSQI, p < 0.001; ESS, p < 0.001; ISI, p < 0.001). Additionally, sleep quality and efficiency were related to total and delayed recall (all r values from −0.31 to −0.60, p < 0.05) in aMCI and VCIND.
aMCI and VCIND differ in cognitive function, memory strategy and sleep impairment; these characteristics are helpful to identify and distinguish patients with very early cognitive impairment. Our results also suggest that memory deficits are associated with sleep disturbance in aMCI and VCIND.
The microstructure evolution and mechanical properties of ultrafine-grained (UFG) Al sheets subjected to accumulative roll bonding (ARB) and subsequent cryorolling was studied. Cryorolling can suppress the dynamic softening of UFG Al sheets subjected to ARB at room temperature. After the third ARB pass, the grains are slightly refined as the number of ARB passes increases. However, the grains are significantly refined further during cryorolling. The grain size of 460 nm achieved after the third ARB pass is reduced to 290 nm after two cryorolling passes with total reduction ratio 80%. Sheets subjected to ARB + cryorolling show improved mechanical properties compared to only ARB-processed sheets due to a change in the fraction of high-angle boundaries and elongated grains. The deformation mechanism for ultrafine grains at room temperature is determined by grain boundary sliding or dislocation-based recovery, while it is governed by dislocation glide at cryogenic temperature.
In recent decades, in silico absorption, distribution, metabolism, excretion (ADME), and toxicity (T) modelling as a tool for rational drug design has received considerable attention from pharmaceutical scientists, and various ADME/T-related prediction models have been reported. The high-throughput and low-cost nature of these models permits a more streamlined drug development process in which the identification of hits or their structural optimization can be guided based on a parallel investigation of bioavailability and safety, along with activity. However, the effectiveness of these tools is highly dependent on their capacity to cope with needs at different stages, e.g. their use in candidate selection has been limited due to their lack of the required predictability. For some events or endpoints involving more complex mechanisms, the current in silico approaches still need further improvement. In this review, we will briefly introduce the development of in silico models for some physicochemical parameters, ADME properties and toxicity evaluation, with an emphasis on the modelling approaches thereof, their application in drug discovery, and the potential merits or deficiencies of these models. Finally, the outlook for future ADME/T modelling based on big data analysis and systems sciences will be discussed.
A new species of boreopterid pterosaur from the new fossil locality, Heichengzi, Beipiao, western Liaoning, China allows a reassessment of the Boreopteridae. In this new analysis, three species, Boreopterus cuiae, Boreopterus giganticus n. sp., and Zhenyuanopterus longirostris, are included within the Boreopteridae united by the autopomorphic occurrence of two main tooth morphologies, an equal length of the tibia and femur, and weak feet. Other taxa previously placed within the Boreopteridae are not in a monophyletic group with the former three species. Boreopterus has fewer teeth and a shorter tooth row than that in Zhenyuanopterus. This new Boreopterus species has a large size, a piriform orbit, an extensively fenestrated lacrimal, and a posteriorly directed lacrimal process, that differs from Boreopterus cuiae.