Objective： Dementia is the fourth most common cause of death in developed countries. The relationship between plasma lipids and cognitive function is complex and controversial. Due to the increasing ...life expectancy of the population, there is an urgent need to control vascular risk factors and to identify therapies to prevent and treat both cognitive impairment and dementia. Here, we reviewed the eff＇ects of plasma lipids and statins on cognitive function. Data Sources： We searched the PubMed database for research articles published through November 2017 with key words including ＂plasma lipids,＂ ＂hyperlipidemia,＂ ＂hypercholesterolemia,＂ ＂statins,＂ and ＂cognition function.＂ Study Selection： Articles were retrieved and reviewed to analyze the effects of plasma lipids and statins on cognitive function and the mechanisms underlying these effects. Results： Many studies have examined the relationship between plasma lipids and cognitive function, but no definitive conclusions can be drawn. The mechanisms involved may include blood-brain barrier injury, the influence on small blood vessels in the brain, the influence on amyloid deposition, and a neuroprotective effect. To date, most studies of statins and cognition have been observational, with few randomized controlled trials. Therefore, finn conclusions regarding whether mid- or long-term statin use affects cognition function and dementia remain elusive. However, increasing concern exists that statins may be a causative factor for cognitive problems. These adverse eff＇ects appear to be rare and likely represent a yet-to-be-defined vulnerability in susceptible individuals. Conclusions： The association between plasma lipids and cognition, the mechanism of the influence of plasma lipids on cognitive function, and the association between statins and cognitive function are complex issues and currently not fully understood. Future research aimed at identifying the mechanisms that underlie the effects of plasma lipids and statins on cognition will not only provide important insight into the causes and interdependencies of cognitive impairment and dementia, but also inspire novel strategies for treating and preventing these cognitive disorders.
A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid‐catalyzed imine formation and transfer hydrogenation cascade process was ...developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.
Chiral BINAMs on demand: A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.
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Nanoformulations with advantages in drug delivery, safety and pharmacodynamics have been booming as a promising strategy for cancer therapy. However, the traditional nanocarrier still ...suffers from the low drug loading capacity, potential systematic toxicity, unclear metabolism, and other uncertainties. To overcome these issues, carrier-free nanodrugs with desirable bioactivity were developed rapidly and drawn considerable attention. Meanwhile, the multifunctional self-delivery nanoarcheticture fabricated by a simple and “green” method, has significant advantages in synergistic cancer therapy and inhibition of multidrug resistant (MDR). Till now, carrier-free nanoparticles for tumor theranostics, phototherapy, chemotherapy, diagnose and synergistic therapy, have made outstanding progress. In this review, we make an integrated and exhaustive overview of lately reports on carrier-free nanodrug delivery systems formed by several active agents. We summarize the self-assembly and modified strategies, with emphasis on application superiority of carrier-free nanocrystal, and give new insight into the establishment of ideal nanosystems for cancer treatment.
Background
Studies in adults have shown that low baseline muscle mass at intensive care unit (ICU) admission was associated with poor clinical outcomes. However, no information on the relationship ...between baseline muscle quality or mass and clinical outcomes in critically ill children was found.
Methods
3775 children were admitted to the pediatric ICU (PICU), 262 were eligible for inclusion. Abdominal computed tomography was performed to assess baseline skeletal muscle mass and quality. Patients were categorized to normal or low group based on the cutoff value for predicting hospital mortality of the skeletal muscle index (SMI; 30.96 cm2/m2) and skeletal muscle density (SMD; 41.21 Hounsfield units).
Results
Body mass index (BMI) (18.07 ± 4.44 vs 15.99 ± 4.51) and BMI‐for‐age z score (0.46 −0.66 to 1.74 vs −0.87 −1.69 to 0.05) were greater in the normal‐SMI group, the length of PICU stay was longer in the low‐SMI group (16.00 days 8.50–32.50 vs 13.00 days 7.50–20.00), and the in‐PICU mortality rate in the normal‐SMI group (10.00%) was lower than the low‐SMI group (22.6%). Children with low SMD had a higher in‐PICU mortality rate (25.6% vs 7.7%), were younger (36.00 months 12.00–120.00 vs 84.00 months 47.50–147.50) and weighed less (16.40 kg 10.93–37.25 vs 23.00 kg 16.00–45.00). Mortality was greater in patients with lower SMD and prolonged hospital stay (log‐rank, P = 0.007). SMD was an independent predictor for length of PICU stay and in‐PICU mortality.
Conclusions
Low baseline skeletal muscle quality in critically ill children is closely tied with a higher in‐PICU mortality and longer PICU stay and is an independent risk factor for unfavorable clinical outcomes.
We report a flame‐reaction method to synthesize high‐performance SmxCoy (x=1, y=5; x=2, y=17) particles on a multigram scale. This flame reaction allows the controlled decomposition of Sm(NO3)3 and ...Co(NO3)2 to 320 nm SmCo‐O (SmCoO3 + Co3O4) particles. A 5.8 g sample of SmCo3.8‐O particles was coated with CaO and then reduced at 900 °C by Ca to give 4.2 g of 260 nm SmCo5 particles. The SmCo5 particles are strongly ferromagnetic and the aligned particles in epoxy resin exhibit a large room‐temperature coercivity (Hc) of 41.8 kOe and giant (BH)max (maximum magnetic energy product) of 19.6 MGOe, the highest value ever reported for SmCo5 made by chemical methods. This synthesis can be extended to synthesize Sm2Co17 particles, providing a general approach to scaling up the synthesis of high‐performance SmxCoy nanomagnets for permanent magnet applications.
Playing with fire: A flame reaction is used to prepare SmCo–oxide particles that are further reduced to form strongly ferromagnetic SmxCoy particles. The 260 nm SmCo5 particles can be embedded in epoxy resin and aligned to show a large room‐temperature coercivity (Hc=41.8 kOe) and high magnetic energy product (19.6 MGOe).
Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an ...important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β‐catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β‐catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.
Huangqi decoction (HQD), a classic traditional herbal medicine, has been used for liver fibrosis, but its effect on intrahepatic chronic cholestatic liver injury remains unknown.
In the present ...study, we investigated the hepatoprotective effect of HQD and the underlying molecular mechanisms in 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine (DDC)-induced chronic cholestatic mice.
The DDC-induced cholestatic mice were administrated HQD for 4 or 8 weeks. Serum biochemistry and morphology were investigated. The serum and liver bile acid (BA) levels were detected by ultra performance liquid chromatography-tandem mass spectrometry. The liver expression of BA metabolizing enzymes and transporters, and inflammatory and fibrotic markers was measured by real-time polymerase chain reaction, western blotting, and immunohistochemistry.
HQD treatment for 4 or 8 weeks ameliorated DDC-induced liver injury by improving impaired hepatic function and tissue damage. HQD treatment for 8 weeks further decreased the liver expression of cytokeratin 19, tumor growth factor (TGF)-β, collagen I, and α-smooth muscle actin, and ameliorated ductular reaction and liver fibrosis. HQD markedly decreased the accumulation of serum and liver BA. The expression of BA-metabolizing enzymes, cytochrome P450 2b10 and UDP glucuronosyltransferase 1 A1, and multidrug resistance-associated protein 2, Mrp3, and Mrp4 involved in BA homeostasis was increased by 4 weeks of HQD treatment. The expression of BA uptake transporter Na+-taurocholate cotransporting polypeptide was decreased and that of Mrp4 was increased after 8 weeks of HQD treatment. Nuclear factor-E2-related factor-2 (Nrf2) was remarkably induced by HQD treatment. Additionally, HQD treatment for 8 weeks decreased the liver expression of inflammatory factors, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1, and intracellular adhesion molecule-1. HQD suppressed the nuclear factor (NF)-κB pathway.
HQD protected mice against chronic cholestatic liver injury and biliary fibrosis, which may be associated with the induction of the Nrf2 pathway and inhibition of the NF-κB pathway, ameliorating BA-stimulated inflammation.
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Abstract
Background
To evaluate global burden of refraction disorders by year, age, region, gender, socioeconomic status and other national characteristics in terms of disability adjusted life years ...(DALYs) and prevalence from Global Burden of Disease (GBD) study 2019 and World Bank Open Data 2019.
Methods
Global, regional, and national DALY numbers, crude DALY rates, age-standardized DALY and prevalence rates of refraction disorders were acquired from the GBD study 2019. Mobile cellular subscriptions, urban population, GDP per capita, access to electricity and total fertility rate were obtained from the World Bank to explore the factors that influenced the health burden of refraction disorders. Kruskal-Wallis test, linear regression and multiple linear regression were performed to evaluate the associations between the health burden with socioeconomic levels and other national characteristics. Wilcoxon Signed-Rank Test was used to investigate the gender disparity.
Results
Globally, age-standardized DALY rates of refraction disorders decreased from 88.9 (95% UI: 60.5–120.3) in 1990 to 81.5 (95% UI: 55.0–114.8) in 2019, and might fall to 73.16 (95% UI: 67.81–78.51) by 2050. Age-standardized prevalence rates would also reduce to 1830 (95% UI: 1700–1960) by 2050, from 2080 (95% UI: 1870–2310) in 1990 to 1960 (95% UI: 1750–2180) in 2019. In low SDI region, age-standardized DALY rates (equation:
Y
= 114.05*X + 27.88) and prevalence rates (equation: Y = 3171.1*X + 403.2) were positively correlated with SDI in linear regression respectively. East Asia had the highest blindness rate caused by refraction disorders in terms of age-standardized DALY rates (11.20, 95% UI: 7.38–16.36). Gender inequality was found among different age groups and SDI regions.
Conclusion
Health burden of refraction disorders decreased in recent years, and may continue to alleviate in the next three decades. Older ages, females and lower socioeconomic status were associated with higher refraction disorders health burden.
Laser additive manufacturing (LAM) is applied to manufacture particles reinforced composites due to its high designability, non-mold and high working flexibility. In this paper, TiC particles ...reinforced Inconel 625 composites were fabricated by LAM technology. Microstructure and chemical compositions of the composites were detected using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Meanwhile, macroscopic Brinell and micro Vickers hardness and in situ tensile test were applied to explore the hardness and fracture behavior of the composites. Results indicate that the microstructure of the composites consist of randomly distributed and partially melted TiC particle reinforcements, and in situ formed MC (M = Nb, Ti and Mo) precipitates with rod like shape appearing in interdendritic areas with a refined microstructure. A MC (M = Nb, Ti and Mo) transition region is observed at the interface between TiC/γ matrix. The hardness of composites was 231 Brinell, 56% higher than that of the laser additive manufactured Inconel 625. However, high hardness and brittleness of reinforcements and precipitates cause unwanted cracks generation during deformation of the materials, and which will later propagate into the matrix and lead to final failure of the composites. The transition region at TiC/γ matrix interface with coherent phase boundary enhanced the bonding strength thus no peeling of particles were observed during the fracture test.
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•A TiC particle and precipitates reinforced Inconel625 composite is proposed.•MC carbides formed both at TiC/γ matrix interface and interdendritic areas.•Initial cracks generate inside TiC due to the coherent bonding at interface.
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