MicroRNA137-loaded lipid nanoparticles regulate synaptic proteins in the prefrontal cortex.

Genome-wide association studies indicate that allele variants in MIR137, the host gene of microRNA137 (miR137), confer an increased risk of schizophrenia (SCZ). Aberrant expression of miR137 and its targets, many of which regulate synaptic functioning, are also associated with an increased risk of SCZ. Thus, miR137 represents an attractive target aimed at correcting the molecular basis for synaptic dysfunction in individuals with high genetic risk for SCZ. Advancements in nanotechnology utilize lipid nanoparticles (LNPs) to transport and deliver therapeutic RNA. However, there remains a gap in using LNPs to regulate gene and protein expression in the brain. To study the delivery of nucleic acids by LNPs to the brain, we found that LNPs released miR137 cargo and inhibited target transcripts of interest in neuroblastoma cells. Biodistribution of LNPs loaded with firefly luciferase mRNA remained localized to the mouse prefrontal cortex (PFC) injection site without circulating to off-target organs. LNPs encapsulating Cre mRNA preferentially co-expressed in neuronal over microglial or astrocytic cells. Using quantitative proteomics, we found miR137 modulated glutamatergic synaptic protein networks that are commonly dysregulated in SCZ. These studies support engineering the next generation of brain-specific LNPs to deliver RNA therapeutics and improve symptoms of central nervous system disorders.

An Exploratory Study of Consumers' Perceptions of Product Types and Factors Affecting Purchase Intentions in the Subscription Economy: 99 Subscription Business Cases.

This study examined changes in consumer perceptions of product types and purchase intentions when a subscription model is introduced for products normally sold on a one-time basis. It then proposed product types likely to affect consumers' purchasing intentions in the subscription economy and product categories best suited for the subscription economy. To this end, an experimental study was conducted with experts and general consumers using 99 subscription business cases. It was found that a regular delivery of products on a subscription basis gradually changes consumer perceptions of the products from utilitarian to hedonic and from search to experience ones. It was also found that consumption motivation is an important predictor of consumer purchase intentions in the subscription economy. In addition, experience-utilitarian and search-utilitarian products were associated with the highest purchase intentions among experts and general consumers, respectively. This suggests that a company's strategy should be adjusted in line with consumers' understanding of the subscription model. Therefore, suppliers need to understand the full implications of the new model, such as changed consumer perceptions and purchasing intentions, and strive to design a subscription model that is suitable for the target segments and product selections.

Developing an Open Innovation Attitude Assessment Framework for Organizations: Focusing on Open Innovation Role Perspective and Locus of Activity.

From an organizational perspective, open innovation (OI) capability assessments are becoming increasingly important. The authors propose that an organization's attitude toward interactive OI activities among OI stakeholders can reveal its degree of capability. This paper aims to focus on an organization's OI attitude measurement scales and develop a framework linked to the role perspectives and loci of OI activities occurring at the organizational level. This research will introduce a practical, theory-based indication of OI assessment by combining a deductive process that identifies organizational OI attitude constructs with an inductive framework development process. First, the authors conducted an extensive literature review of attitude measurement on the execution of OI. Then, they performed empirical data analysis using a large-scale structured attitude assessment survey from individuals in domestic and multi-national corporations (n = 134), which led to the development of questionnaire sets on attitude evaluation. This study contributes to developing an organizational OI attitude assessment scale. Furthermore, based on empirical data analysis, the research framework demonstrated the reliability and validity of the organizational OI attitude measurement scale. Specifically, the scale contains proven questionnaires assessing OI attitudes by interrogating individual actors' impact, behavior, and cognition regarding their organization's OI activities. The organization's three role perspectives (transfer, absorption, and brokerage) and two loci of activities in the OI ecosystem provide six distinct dimensions, suggesting areas of focus for a firm's strategic OI direction.

Gas/Particle Partitioning Constants of Nicotine, Selected Toxicants, and Flavor Chemicals in Solutions of 50/50 Propylene Glycol/Glycerol As Used in Electronic Cigarettes.

For an electronic cigarette (e-cigarette) aerosol with known total particulate matter concentration (TPM, µg/m3), predictions of the fractions of some compound i in the gas and particle phases ( fg, i and fp, i) at equilibrium can be made based on Kp, i (m3/µg), the compound-dependent gas/particle partitioning equilibrium constant. fg, i and fp, i affect the modes and locations of deposition in the respiratory tract. Kp, i depends inversely on (1) the pure compound liquid vapor pressure ( pL, io), (2) mole fraction activity coefficient (ζ i) in the absorbing liquid, and (3) mean molecular weight of the absorbing liquid (MW). Kp, i values were measured at 20 °C for 32 compounds as spiked into simulated e-cigarette liquids prepared as 50/50 mixtures (by weight) of propylene glycol (PG) and glycerol (GL). Kp, i values at 37 °C were estimated. The 32 compounds were nicotine (in free-base form), seven toxicants (propanal, acetone, hydroxyacetone, benzene, toluene, p-xylene, and ethylbenzene), and 24 flavor chemicals (2,3-pentanedione ("acetyl propionyl"), isobutyl acetate, ethyl butyrate, butyl butyrate, isoamyl acetate, 2,3-dimethylpyrazine, 3-methyl-1-butanol, limonene, 2,3,5-trimethylpyrazine, p-cymene, benzaldehyde, ( Z)-3-hexen-1-ol, menthol, 2-acetylpyrrole, benzyl alcohol, methyl salicylate, cinnamaldehyde, methyl anthranilate, (+)-aromadendrene, cinnamyl alcohol, methyl cinnamate, maltol, ethyl maltol, and coumarin). The measured log Kp, i values were found to be generally correlated with literature values of log pL, io; the scatter is caused by variation in ζ i between ∼1 and ∼1000. Kp measurements were attempted, but values were not reported for acetaldehyde, 2,3-butanedione (diacetyl), vanillin, and ethyl vanillin. Acetaldehyde was found to form significant amounts of its cyclic trimer and cyclic tetramer; for diacetyl, the evidence suggested significant amounts of reaction products, possibly hemiketals and ketals with PG/GL, and for vanillin and ethyl vanillin, the Kp values are large and accordingly more difficult to measure. fg values are calculated using a range of Kp and TPM values.

Flavour chemicals in a sample of non-cigarette tobacco products without explicit flavour names sold in New York City in 2015.

BACKGROUND: Youth who experiment with tobacco often start with flavoured products. In New York City (NYC), local law restricts sales of all tobacco products with 'characterising flavours' except for 'tobacco, menthol, mint and wintergreen'. Enforcement is based on packaging: explicit use of a flavour name (eg, 'strawberry') or image depicting a flavour (eg, a fruit) is presumptive evidence that a product is flavoured and therefore prohibited. However, a tobacco product may contain significant levels of added flavour chemicals even when the label does not explicitly use a flavour name. METHODS: Sixteen tobacco products were purchased within NYC in 2015 that did not have explicit flavour names, along with three with flavour names. These were analysed for 92 known flavour chemicals plus triacetin by gas chromatography/mass spectrometry. RESULTS: 14 of the 16 products had total determined flavour chemical levels that were higher (>0.3 mg/g) than in previously studied flavour-labelled products and of a chemical profile indicating added flavour chemicals. CONCLUSIONS: The results suggest that the tobacco industry has responded to sales restrictions by renaming flavoured products to avoid explicitly identifying them as flavoured. While chemical analysis is the most precise means of identifying flavours in tobacco products, federal tobacco laws pre-empt localities from basing regulations on that approach, limiting enforcement options. If the Food and Drug Administration would mandate that all tobacco products must indicate when flavourings are present above a specific level, local jurisdictions could enforce their sales restrictions. A level of 0.1 mg/g for total added flavour chemicals is suggested here as a relevant reference value for regulating added flavour chemicals in tobacco products.

Benzene formation in electronic cigarettes.

BACKGROUND/OBJECTIVE: The heating of the fluids used in electronic cigarettes ("e-cigarettes") used to create "vaping" aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine. METHODS/MAIN RESULTS: Three e-cigarette devices were used: the JUULTM "pod" system (provides no user accessible settings other than flavor cartridge choice), and two refill tank systems that allowed a range of user accessible power settings. Benzene in the e-cigarette aerosols was determined by gas chromatography/mass spectrometry. Benzene formation was ND (not detected) in the JUUL system. In the two tank systems benzene was found to form from propylene glycol (PG) and glycerol (GL), and from the additives benzoic acid and benzaldehyde, especially at high power settings. With 50:50 PG+GL, for tank device 1 at 6W and 13W, the formed benzene concentrations were 1.9 and 750 µg/m3. For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 µg/m3. With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 µg/m3. For tank device 2 at 25W, all values were ≤~100 µg/m3. These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 µg/m3. Thus, the risks from benzene will be lower from e-cigarettes than from conventional cigarettes. However, ambient benzene air concentrations in the U.S. have typically been 1 µg/m3, so that benzene has been named the largest single known cancer-risk air toxic in the U.S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher µg/m3 will not be of negligible risk.