Current technology relies heavily on composite materials, but in most cases, the size of the individual components have been micrometers or larger. The development of nanotechnology is driven in part by the desire to prepare materials that are only a few nanometers in size or that are made from components in the sub-micrometer regime. Improved preparations of various examples of monodisperse, [1] porous, [2] hollow, and/or core/shell [3] metal and semiconductor nanoparticles or nanowires [4] have been developed. We report here the use of a simple and scalable technology, ultrasonic spray pyrolysis (USP), [2e,5] to prepare porous, hollow, or ball-in-ball nanomaterials ( Fig. 1 and Supporting Information Fig. S1). In addition, we have investigated the cell toxicity (cytotoxicity) of these nanomaterials, in keeping with the growing concern of health effects that manmade nanoparticles could have now and in the near future.[6]Our interest in USP stems from our long standing work on the chemical and physical effects of ultrasound. [7a,b] In liquids irradiated with high-intensity ultrasound, acoustic cavitation produces high-energy chemistry through intense local heating inside the gas phase of collapsing bubbles in the liquid. [7] There are diverse applications of such sonochemistry, including the preparation of nanostructured materials and nanoparticles. USP presents an interesting inversion of the cavitation process.[2e,5j,k] Both confine the chemical reactions to isolated sub-micrometer reaction zones, but sonochemistry does so in a heated gas phase within a liquid, while USP uses a hot liquid droplet (or resulting heated solid particle) carried by a gas flow. Thus, we view USP as a method of phase-separated synthesis, in our cases, using sub-micrometer-sized droplets as isolated chemical reactors for nanomaterial synthesis. While USP has been used to create both titania and silica spheres separately, [2e,5b-d] there are no prior reports of titaniasilica composites. We have now produced such nanocomposites, and by further manipulation, generated various porous structures with fascinating morphologies (Figs. 1 and 2 and Supporting Information Fig. S3). As described in more detail in the Experimental section, a precursor solution was nebulized using a commercially available household ultrasonic humidifier (1.7 MHz ultrasound generator), and the resulting mist was carried in a gas stream through a glass tube in a hot furnace. After exiting the hot zone, spherical particles a few hundred nanometers in size (hereon referred to as microspheres) were collected in a water-filled bubbler as an aqueous colloidal solution. The microspheres were then isolated from this solution by centrifugation. Morphology, size distribution, and composition were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning TEM (STEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Cytotoxicity was tested with several whole mammalian cell assays.[8] Small molecules were also de...

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimulated macrophages through the synthesis of the CDK5-binding partner and activator p35. Degradation of p35 released the inhibition on anti-inflammatory signaling mediated by CDK5-p35 complexes. The transiently active CDK5-p35 complexes limited the LPS-stimulated phosphorylation and activation of various mitogen-activated protein kinases (MAPKs), thereby preventing the premature production of SOCS3 (suppressor of cytokine signaling 3), an inhibitor of inflammatory responses in macrophages, and IL-10. Furthermore, we showed that dextran sodium sulfate failed to induce colitis in p35-deficient mice, which was associated with the enhanced production of IL-10 by macrophages. Together, our results suggest that CDK5 enhances the inflammatory function of macrophages by inhibiting the MAPK-dependent production of IL-10.

Aim The purpose of this study was to identify the midlife and later life factors affecting reversion from mild cognitive impairment to normal cognition after 4 years. Methods We analyzed data from the 2012 and 2016 Korean Longitudinal Study of Aging. The participants of this study were Korean community‐dwelling adults aged ≥45 years who showed mild cognitive impairment in 2012. They were divided into midlife (<65 years) and later life (≥65 years) based on their age in 2012. Cognitive function was assessed by the Korean Mini‐Mental State Examination in 2016. Multiple logistic regression analysis was carried out to determine the factors affecting reversion by age group. Results Among participants with mild cognitive impairment, 52.0% in midlife and 26.6% in later life reverted to normal cognition after 4 years. In midlife, higher education (OR 1.97, 95% CI 1.15–3.36), fewer chronic diseases (OR 0.78, 95% CI 0.61–0.99), lower levels of depressive symptoms (OR 0.95, 95% CI 0.90–0.99) and higher participation in social activities (OR 1.91, 95% CI 1.27–2.87) were significantly associated with reversion. In later life, higher baseline cognitive function (OR 1.30, 95% CI 1.14–1.47) and higher participation in social activities (OR 1.35, 95% CI 1.02–1.79) were significantly associated with reversion. Conclusions The reversion rate in midlife was higher than that of later life. More modifiable factors affecting reversion were found in midlife, suggesting that assessment and intervention at an early age should be considered. Geriatr Gerontol Int 2019; 19: 1129–1135.

Leaders for the Future by Brain Korea 21 (BK 21) four project,

Neuregulin-1 (NRG-1) is a ligand of the epidermal growth factor receptor (erbB), and its interaction involves activation of the glutamatergic N-methyl-Daspartate receptor, which increases the expression of the β2 subunit of the γ- aminobutyric acid receptor and subunits of the nicotinic acetylcholine receptor. In the dentate gyrus of 14-month-old Tg2576 mice, NRG-1 was strongly expressed compared with age-matched controls. The supernatant of oligomeric amyloid β peptide (Aβ42)-treated glial cells enhanced the Aβ42;-induced cytotoxic effects, but the expression of Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand in microglial cells was not changed upon cytotoxic treatment. This suggests that the oligomeric form of Aβ42 toxicity is not related to apoptosis, which is mediated by cell-to-cell interaction. During the 24-h incubation, the secretion of the soluble form of NRG-1 was increased, but interleukin 6 secretion was not changed. Further, soluble NRG-1 increased Aβ42-induced toxicity. In conclusion, soluble NRG-1 significantly enhanced oligomeric Aβ42-induced toxicity through the activation of endoplasmic reticulum stress by the increase of a phospho-translation initiation factor 2 alpha (p-eIF2α).