Esketamine, one of the few non-opioid potent analgesics, has demonstrated efficacy in the treatment of various chronic pain, particularly neuropathic pain. However, its potential clinical ...applications are confined due to its short half-life and severe side effects including delirium, hallucinations, and other psychiatric symptoms. Here, we reported a nanosized drug delivery system for sustained-release esketamine based on polylactic-co-glycolic acid (PLGA) nanoparticles and hyaluronic acid (HA) hydrogel.
In this study, esketamine in the delivery system was continuously released in vitro for at least 21 days, and spinal nerve root administration of the delivery system successfully attenuated (spinal nerve ligation) SNL-induced pain hypersensitivity for at least 14 days. Notably, the excitability of neurons in murine dorsal root ganglion (DRG) was inhibited and the activation of astrocytes in the spinal cord was additionally reduced after administration. Finally, there was no obvious pathophysiological change in the nerves at the administration site after treatment at 14 days.
These results indicate that the sustained-release esketamine based on the nanoparticle-hydrogel delivery system can safely produce a lasting analgesic effect on SNL mice, and its mechanism might be related to modulating the activation of astrocytes in the spinal cord and inhibiting the excitability of neurons in DRG.
Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA ...probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.
The demand for healthy old-age care is growing rapidly in China. The traditional old-age care model can no longer meet elderly patients’ demands for medical care and old-age care. To promote the ...development of medical care-integrated old-age care, a solution covering multiple aspects is necessary. In the context of the global development of healthy aging, China recently issued many policies to integrate old-age care with medical care, establishing protection for a large number of disabled elderly people. The Integrated Care of Older People (ICOPE) project is an international program developed by the World Health Organization. This paper reviews China’s medical and old-age care integration model and the opportunities and challenges in implementing the ICOPE in the context of healthy aging in China.
Previous studies have shown that diffusion tensor imaging suggests a diffuse loss of white matter integrity in people with white matter hyperintensities or lacunes. The purpose of this study was to ...investigate whether the presence of cerebral microbleeds and their distribution are related to the integrity of white matter microstructures.
The study comprised 982 participants who underwent brain MR imaging to determine microbleed status. The cross-sectional relation between microbleeds and the microstructural integrity of the white matter was assessed by 2 statistical methods: a multilinear regression model based on the average DTI parameters of normal-appearing white matter and Tract-Based Spatial Statistics analysis, a tract-based voxelwise analysis. Fiber tractography was used to spatially describe the microstructural abnormalities along WM tracts containing a cerebral microbleed.
The presence of cerebral microbleeds was associated with lower mean fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity, and the association remained when cardiovascular risk factors and cerebral small-vessel disease markers were further adjusted. Tract-Based Spatial Statistics analysis indicated strictly lobar cerebral microbleeds associated with lower fractional anisotropy, higher mean diffusivity, and higher radial diffusivity in the internal capsule and corpus callosum after adjusting other cerebral small-vessel disease markers, while only a few voxels remained associated with deep cerebral microbleeds. Diffusion abnormalities gradients along WM tracts containing a cerebral microbleed were not found in fiber tractography analysis.
Cerebral microbleeds are associated with widely distributed changes in white matter, despite their focal appearance on SWI.
Natural deep eutectic solvents (NADESs) are efficient in extracting natural products. However, traditional organic solvents are toxic in the extraction of anthraquinones from
Rheum palmatum
L. To ...solve this problem, we applied natural deep eutectic solvent ultrasound-assisted extraction in this study for the extraction of total anthraquinones from
R. palmatum
L. Principal component analysis revealed that the selected NADES which consisted of lactic acid, glucose and water (LGH), was highly efficient in extracting anthraquinones from
R. palmatum
L. The ratio of lactic acid/glucose and the addition of water in LGH were investigated
via
a single-factor experiment. With a lactic acid/glucose ratio of 5 : 1 (mol/mol), and 10% of water (v/v), LGH had a high extraction yield to anthraquinones. Optimized by response surface methodology (RSM), the optimized extraction conditions of extraction time, extraction temperature and solvent-to-solid ratio of 1.5 h, 82 °C and 26 mL g
−1
, respectively. Under optimum conditions, the extraction yields of aloe-emodin, rhein, emodin, chrysophanol, physcion and total anthraquinones were 2.60 ± 0.01, 5.78 ± 0.02, 2.21 ± 0.02, 5.87 ± 0.02, 8.81 ± 0.01 and 25.27 ± 0.07 mg g
−1
, respectively. The enrichment and separation of five anthraquinones in LGH extraction solution were efficiently achieved using DM130 macroporous resin, with purities of 90.98%, 96.67%, 92.37%, 95.80% and 91.61% as indicated by HPLC, and recovery yields of 84.08%, 79.51%, 84.96%, 81.83% and 78.35%, respectively. LGH was environmentally friendly and highly efficient in extracting anthraquinones from
R. palmatum
L., and NADESs showed potential for the extraction of effective components from natural products.
Natural deep eutectic solvents ultrasound-assisted extraction (NADES-UAE) was applied to extract total anthraquinones from
Rheum palmatum
L.
To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous ...teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism–related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen–positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.
Plasmonic responses in materials with actively tunable elliptic-to-hyperbolic transition are rare in nature. Based on ab-initio calculations, we have theoretically predicted that Janus black arsenic ...phosphorus (bAsP) supports both elliptic and hyperbolic in-plane surface plasmon polaritons in the infrared after being doped with electrons. In the elliptic regime, anisotropic plasmonic responses have been observed, which can be explained by the anisotropic dispersions at the bottom of the conduction bands. In the hyperbolic regime, the total permittivity along the armchair/zigzag edge is negative/positive, which is the result of positive interband permittivities and largely different Drude plasma frequencies along two directions making the total permittivities change signs at different photon energies. In this material, changing the topology (elliptic or hyperbolic) of the plasmonic responses via doping is possible. Then, strains along the zigzag and armchair directions have been applied to modify the band structures as well as the plasmonic responses. Since plasmonic responses are mostly related to the bands near the Fermi energy, a relatively small strain along the zigzag direction can make bAsP become an indirect-bandgap material and change the Drude plasma frequencies under proper doping. With both strain and doping present in this material, we have even found a special case of hyperbolicity where the total permittivity in the zigzag/armchair direction is negative/positive, which is opposite to the normal case. In the end, we have extended our investigations to bAsP-graphene heterostructures. Since bAsP is a Janus material, such direct contact can change the Fermi energy through charge transfer making this heterostructure support strong plasmons without extra doping. Our investigations propose bAsP as a promising Janus material platform for plasmonic applications.
Background
Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole.
Objectives
To ...evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy.
Search strategy
A systematic literature search was conducted to identify relevant studies published from inception until April 2019.
Selection criteria
Relevant English‐language citations using the terms oral fluconazole and pregnancy in humans.
Data collection
Two reviewers independently ed data and assessed study quality.
Main results
Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio OR 1.09, 95% CI 0.99–1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high‐dose users (>150 mg) (OR 1. 19, 95% CI 1.01–1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09–1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1–1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71–6.74, P < 0.001; n = 2) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (OR 1.99, 95% CI 1.38–2.88, P < 0.001; n = 3).
Conclusions
Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven.
Tweetable
Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.
Tweetable
Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.
This paper reports probably the first systematic experimental investigation of the influences of lateral inertia confinement, end friction confinement and aggregates in high-speed impact tests on ...dynamic compressive properties of concrete. The influences of the concerned factors on the dynamic increase factor (DIF) are discussed. The proposed DIF relations in Hao and Hao 36 are verified by the experimental data in this study. The results confirm the observations made before based on numerical simulations that lateral inertia confinement effect is dependent on the specimen diameter and strain rate. The influences of aggregate size and volume to DIF are considerable, and aggregates cannot be neglected in experimental or numerical studies. It also confirms that the end friction confinement effect is sensitive to the specimen geometry and strain rate. The equation proposed in Hao et al. 40 based on numerical simulations satisfactorily removes the friction confinement effect on the DIF of concrete material strength obtained in impact test.
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