N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4 positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu4 PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu4 expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([11C]3) as a PET radiotracer for mGlu4, and characterized its biological properties in Sprague Dawley rats. [11C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [11C]CH3I. Total synthesis time was 38±2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [11C]3 was obtained in 27.7±5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [11C]CO2. The radiochemical purity of [11C]3 was >99%. Specific activity was 188.7±88.8 GBq/μmol (n = 4) at the end of synthesis (EOS). PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu4 modulator (4) to investigate specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [11C]3 (peak activity between 1-3 min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu4 modulator 4 showed 22-28 % decrease of [11C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu5. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu4, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.

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EI produced completely reversible and dose-dependent nerve conduction inhibition, which had slower onset and faster recovery compared with those produced by lidocaine.

Open innovation communities (OICs) can help enterprises make full use of external knowledge resources from users, but problems such as low user participation and low conversion rate of creative ideas impact the efficiency of OICs. Most studies on this topic employ qualitative or empirical methods from a static perspective, but ignore the effect of interaction between enterprises and users as well as the cumulative effect of time. A discussion on the dynamic evolution process of open innovation is lacking. Based on a review of the literature on OICs, innovation performance, and system dynamics, this study proposes a conceptual model of innovation performance impact, which comprises the knowledge management, governance mechanism, and user behavior subsystems. Xiaomi’s OIC in China was selected as the research object, and relevant data were collected through a web spider. According to the system dynamics modeling method, a causal relationship analysis was carried out on the three aforementioned interrelated subsystems. Then, a stock flow chart with 32 variables was constructed to determine the initial values and calculation equations for each variable. Finally, the model was constructed and verified using Vensim PLE software. The simulation results were as follows. (1) The number of product releases in the Xiaomi OIC was positively correlated with the number of posts, comments, and views. Compared with user interaction behavior (i.e., commenting and viewing), the impact of user innovation behavior (i.e., posting) on enterprise innovation performance (i.e., number of patents) is clearer. Specifically, regarding interaction behavior, the impact of the users’ commenting behavior on innovation performance (i.e., number of product releases) was relatively clearer than that of their viewing behavior. (2) Governance mechanism (i.e., R&D investment and management expense), which comprises technical and organizational mechanisms, positively affected the innovation performance of enterprises. Compared with the organizational mechanism (i.e., management expense), the impact of the technical mechanism (i.e., R&D investment) on the innovation performance was clearer. (3) Governance mechanism helped to increase the number of users in the OIC, and, in turn, affected the user innovation and interaction behavior. (4) The technical mechanism positively affected knowledge application capability, which, in turn, had a positive impact on the innovation performance of enterprises. Based on these findings, management strategies are proposed for the establishment and development of OICs.

In the present study, non-waxy corn starch was processed by different freeze-thawing temperatures and cycles. The effects of freeze-thawing treatment on the surface structure, granules particle size, Maltese crosses, crystalline, and thermal properties of non-waxy corn starch were investigated. The number of pores on the surface of starch granules increased with freeze-thawing cycles. The granule size, crystalline intensity and degree, gelatinization temperatures, and enthalpy values of corn starch decreased with freeze-thawing cycles increased. The Maltese crosses indicated that loss of Maltese cross increased when freezethawing cycles increased, but decreased with increase in temperature. Moreover, clear cracks and big pores were observed on the surface of starch granules, and smaller granule size and lower thermal parameters were obtained in the distorted corn granules caused by the changes in crystalline structure under appropriate treatment (À20°C freezing and 25°C thawing, 20 cycles). Freeze-thawing treatment significantly increased the porosity of corn starch, which indicated that it can improve adsorptive capacity of starches. Therefore, freeze-thawing method is potentially very useful to produce porous starch as carrier or absorbent for food and medicine. These findings could have important applications in starch modification industry.

In this novel and minimally traumatic model, the anesthetic partial pressure delivered to the spinal cord governed the suppression of movement in response to noxious stimulation. The results indicate that the spinal cord is the primary mediator of immobility and that the brain plays little or no role.

Many studies have reported long-term modulation of metabotropic glutamate receptor 5 (mGluR5) by inflammatory processes and a pharmacological modulation of mGluR5 is known to regulate anxiety level. However, it is not known if non-pharmacological modulation of mGluR5 by inflammation impaired the unconditional level of anxiety. In this study, we investigated this relation in LPS prenatal immune challenge (120μg/kg, 3x i.p. injection in late gestation), a developmental model of neuroinflammation in which some studies have reported hypo-anxious phenotype. Using positron emission tomographic imaging (PET) approaches, we have demonstrated a decrease in the binding potential of [18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB, a radioligand for mGluR5) in hippocampus of adolescent offspring prenatally exposed to LPS, without significant change in the binding of [11C]peripheral benzodiazepine receptor 28 ([11C]PBR28), an inflammatory marker. In addition, dark-light box emergence test revealed a lower level of anxiety in LPS-exposed offspring and this behavioural phenotype was associated with the binding potential of [18F]FPEB in hippocampus. These results confirm that neuroinflammation during developmental phase modulates the physiology of mGluR5 and this alteration can be associated with behavioural phenotype related to anxiety. In addition, this study supports a hypotheses that mGluR5 could be used as a diagnostic target in anxiety.

mGlu5 play an important role in physiology and pathology to various central nervous system (CNS) diseases. Several positron emission tomography (PET) radiotracers have been developed to explore the role of mGlu5 in brain disorders. However, there are no single photon emission computed tomography (SPECT) radioligands for mGlu5. Here we report development of [(123)I]IPEB ([(123)I]1) and [(123)I]IMPEB ([(123)I]2) as mGlu5 radioligands for SPECT. [(123)I]1 and [(123)I]2 were produced by copper(I) mediated aromatic halide displacement reactions. The SPECT imaging using mouse models demonstrated that [(123)I]1 readily entered the brain and accumulated specifically in mGlu5-rich regions of the brain such as striatum and hippocampus. However, in comparison to the corresponding PET tracer [(18)F]FPEB, [(123)I]1 showed faster washout from the brain. The binding ratios of the striatum and the hippocampus compared to the cerebellum for [(123)I]1 and [(18)F]FPEB were similar despite unfavorable pharmacokinetics of [(123)I]1. Further structural optimization of 1 may lead to more viable SPECT radiotracers for the imaging of mGlu5.