Boosting Photoredox Catalysis Using a Two-Dimensional Electride as a Persistent Electron Donor.

Electrides, which have excess anionic electrons, are solid-state sources of solvated electrons that can be used as powerful reducing agents for organic syntheses. However, the abrupt decomposition of electrides in organic solvents makes controlling the transfer inefficient, thereby limiting the utilization of their superior electron-donating ability. Here, we demonstrate the efficient reductive transformation strategy which combines the stable two-dimensional [Gd2C]2+·2e- electride electron donor and cyclometalated Pt(II) complex photocatalysts. Strongly localized anionic electrons at the interlayer space in the [Gd2C]2+·2e- electride are released via moderate alcoholysis in 2,2,2-trifluoroethanol, enabling persistent electron donation. The Pt(II) complexes are adsorbed onto the surface of the [Gd2C]2+·2e- electride and rapidly capture the released electrons at a rate of 107 s-1 upon photoexcitation. The one-electron-reduced Pt complex is electrochemically stable enough to deliver the electron to substrates in the bulk, which completes the photoredox cycle. The key benefit of this system is the suppression of undesirable charge recombination because back electron transfer is prohibited due to the irreversible disruption of the electride after the electron transfer. These desirable properties collectively serve as the photoredox catalysis principle for the reductive generation of the benzyl radical from benzyl halide, which is the key intermediate for dehalogenated or homocoupled products.

Exposure to lead on expression levels of brain immunoglobulins, inflammatory cytokines, and brain-derived neurotropic factor in fetal and postnatal mice with autism-like characteristics.

Autism spectrum disorders (ASD) are neurodevelopmental disorders, and their incidence is increasing worldwide. Increased exposure to environmental metal lead (Pb) has been proposed as a risk factor associated with ASD. In the present study, BTBR T+ tf/J (BTBR) mice with ASD-like behavioral characteristics and control FVB mice were exposed gestationally and/or neonatally to Pb, and compared with highly social FVB mice to investigate neuroimmunological abnormalities. IgG1 and IgG2a levels in fetal brains from BTBR dams exposed to Pb (BTBR-Pb) were significantly higher than those of BTBR-controls (BTBR-C). However, this change did not occur in FVB mice exposed to Pb. The IgG1:IgG2a ratio was higher in both fetal and postnatal brains of BTBR mice compared to FVB animals regardless of Pb exposure. The IL-4:IFN-γ ratio was elevated in BTBR-Pb relative to BTBR-C mice, but this ratio was not markedly affected following Pb exposure in FVB animals. These findings suggest the potential for a Pb-driven predominant TH2-like reactivity profile in brain microenvironment present in BTBR mice. Brain-derived neurotrophic factor was decreased in fetal and postnatal BTBR-Pb brains relative to BTBR-C brains but not in FVB-Pb relative to FVB-C mice. Taken together, data demonstrate that Pb exposure might contribute to developmental brain abnormalities associated with ASD, particularly in individuals with genetic susceptibility to ASD.

Protective effect of Paeoniae radix alba root extract on immune alterations in mice with atopic dermatitis.

Atopic dermatitis is a progressive inflammatory disease characterized by type 2 helper T cell (TH2) reactivity. The aim of this study was to examine the therapeutic effects of Paeoniae radix alba root extract using a murine model of atopic dermatitis. Atopic dermatitis was induced in a murine model characterized by immune alterations skewed toward TH2 reactivity and pathophysiological dermal alterations which resemble human atopic dermatitis. The root extract at 1% or 6% was applied to the mouse dorsal skin for 3 weeks following induction of atopic dermatitis. Splenocytes were stimulated with immobilized anti-CD3 for 48 h to measure cytokine production. Levels of serum IgE, IgG1, and IgG2a were quantitated. Epidermal thickness and numbers of skin mast cells were determined. Mice in which atopic dermatitis was induced displayed increased numbers of skin mast cells, increased frequency of scratching, elevated serum IgE levels, increased ratios of IgG1 to IgG2a, and ratios of IL-4 to IFN-γ. The frequency of scratching was significantly decreased following application of 1% or 6% extract for 1 week. The root extract also reversed TH2 skewing, as serum IgE levels, ratio of serum IgG1 to IgG2a, and ratio of IL-4 to IFN-γ production by in vitro-stimulated splenocytes were all suppressed following application of 1% or 6% extract for 3 weeks. Taken together Paeoniae radix alba root extract is suggested to reverse the immunological alterations and skin manifestations symptoms found in atopic dermatitis.

Tailoring Hydrophobic Interactions between Probes and Amyloid-ß Peptides for Fluorescent Monitoring of Amyloid-ß Aggregation.

Despite their unique advantages, the full potential of molecular probes for fluorescent monitoring of amyloid-ß (Aß) aggregates has not been fully exploited. This limited utility stems from the lack of knowledge about the hydrophobic interactions between the molecules of Aß probes, as well as those between the probe and the Aß aggregate. Herein, we report the first mechanistic study, which firmly establishes a structure-signaling relationship of fluorescent Aß probes. We synthesized a series of five fluorescent Aß probes based on an archetypal donor-acceptor-donor scaffold (denoted as SN1-SN5). The arylamino donor moieties were systematically varied to identify molecular factors that could influence the interactions between molecules of each probe and that could influence their fluorescence outcomes in conditions mimicking the biological milieu. Our probes displayed different responses to aggregates of Aß, Aß40 and Aß42, two major isoforms found in Alzheimer's disease: SN2, having pyrrolidine donors, showed noticeable ratiometric fluorescence responses (Δν = 797 cm-1) to the Aß40 and Aß42 samples that contained oligomeric species, whereas SN4, having N-methylpiperazine donors, produced significant fluorescence turn-on signaling in response to Aß aggregates, including oligomers, protofibrils, and fibrils (with turn-on ratios of 14 and 10 for Aß42 and Aß40, respectively). Mechanistic investigations were carried out by performing field-emission scanning electron microscopy, X-ray crystallography, UV-vis absorption spectroscopy, and steady-state and transient photoluminescence spectroscopy experiments. The studies revealed that the SN probes underwent preassembly prior to interacting with the Aß species and that the preassembled structures depended profoundly on the subtle differences between the amino moieties of the different probes. Importantly, the studies demonstrated that the mode of fluorescence signaling (i.e., ratiometric response versus turn-on response) was primarily governed by stacking geometries within the probe preassemblies. Specifically, ratiometric fluorescence responses were observed for probes capable of forming J-assembly, whereas fluorescence turn-on responses were obtained for probes incapable of forming J-aggregates. This finding provides an important guideline to follow in future efforts at developing fluorescent probes for Aß aggregation. We also conclude, on the basis of our study, that the rational design of such fluorescent probes should consider interactions between the probe molecules, as well as those between Aß peptides and the probe molecule.

Visible light-driven photogeneration of hydrogen sulfide.

The combined use of a singlet oxygen photosensitizer and 1,3-diarylisobenzothiophene enables efficient generation of hydrogen sulfide under visible light illumination.

Comparison of alkaline phosphatase activity of MC3T3-E1 cells cultured on different Ti surfaces: modified sandblasted with large grit and acid-etched (MSLA), laser-treated, and laser and acid-treated Ti surfaces.

PURPOSE: In this study, the aim of this study was to evaluate the effect of implant surface treatment on cell differentiation of osteoblast cells. For this purpose, three surfaces were compared: (1) a modified SLA (MSLA: sand-blasted with large grit, acid-etched, and immersed in 0.9% NaCl), (2) a laser treatment (LT: laser treatment) titanium surface and (3) a laser and acid-treated (LAT: laser treatment, acid-etched) titanium surface. MATERIALS AND METHODS: The MSLA surfaces were considered as the control group, and LT and LAT surfaces as test groups. Alkaline phosphatase expression (ALP) was used to quantify osteoblastic differentiation of MC3T3-E1 cell. Surface roughness was evaluated by a contact profilometer (URFPAK-SV; Mitutoyo, Kawasaki, Japan) and characterized by two parameters: mean roughness (Ra) and maximum peak-to-valley height (Rt). RESULTS: Scanning electron microscope revealed that MSLA (control group) surface was not as rough as LT, LAT surface (test groups). Alkaline phosphatase expression, the measure of osteoblastic differentiation, and total ALP expression by surface-adherent cells were found to be highest at 21 days for all three surfaces tested (P<.05). Furthermore, ALP expression levels of MSLA and LAT surfaces were significantly higher than expression levels of LT surface-adherent cells at 7, 14, and 21 days, respectively (P<.05). However, ALP expression levels between MSLA and LAT surface were equal at 7, 14, and 21 days (P>.05). CONCLUSION: This study suggested that MSLA and LAT surfaces exhibited more favorable environment for osteoblast differentiation when compared with LT surface, the results that are important for implant surface modification studies.

Aberrant IgG isotype generation in mice with abnormal behaviors.

BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Up-regulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG1, IgG2b and IgG3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG1:IgG2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG1:IgG2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brain-reactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice.

Development of a standardized job description for healthcare managers of metabolic syndrome management programs in Korean community health centers.

PURPOSE: This study aimed to develop a job description for healthcare managers of metabolic syndrome management programs using task analysis. METHODS: Exploratory research was performed by using the Developing a Curriculum method, the Intervention Wheel model, and focus group discussions. Subsequently, we conducted a survey of 215 healthcare workers from 25 community health centers to verify that the job description we created was accurate. RESULTS: We defined the role of healthcare managers. Next, we elucidated the tasks of healthcare managers and performed needs analysis to examine the frequency, importance, and difficulty of each of their duties. Finally, we verified that our job description was accurate. Based on the 8 duties, 30 tasks, and 44 task elements assigned to healthcare managers, we found that the healthcare managers functioned both as team coordinators responsible for providing multidisciplinary health services and nurse specialists providing health promotion services. In terms of importance and difficulty of tasks performed by the healthcare managers, which were measured using a determinant coefficient, the highest-ranked task was planning social marketing (15.4), while the lowest-ranked task was managing human resources (9.9). CONCLUSION: A job description for healthcare managers may provide basic data essential for the development of a job training program for healthcare managers working in community health promotion programs.

Design and preliminary results of a metropolitan lifestyle intervention program for people with metabolic syndrome in South Korea.

INTRODUCTION: The Seoul Metabolic Syndrome Management (SMESY) project, a metropolitan lifestyle intervention program aimed at decreasing the risk of metabolic syndrome to the residents of the city, has recently been implemented in 2011. METHODS: Our target population consisted of residents of Seoul who were 30-64 years old. Subjects visiting a Public Health Center were screened for five risk factors for metabolic syndrome and then divided into three groups according to the number of the risk factors: active counseling, for having more than three risk factors; motivational guide, for having one or two; and information support for having none. Members of the active counseling group, the main target of the project, were provided with monthly in-person counseling on health-related lifestyle choices, as well as a follow-up examination every 3 months during the 12-month program. RESULTS: In the active counseling group, subjects showed statistically significant improvements in all five risk factors and the average number of retained risk factors decreased from 3.5 to 2.7. However, the percentage of active counseling group members who attended at least 3 out of the 4 sessions provided was only 11.3%. As for the motivational guide group and the information support group, clinically significant improvements were not observed and the percentage of members who attended all sessions were 10.4% and 11.8%, respectively. CONCLUSIONS: Increased public participation for the ongoing project is expected to lead to great positive changes in the health of people with metabolic syndrome.