COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)—and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited . We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex–COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes—catechol-O-methyltransferase ( As people live in ever-denser population centers, the implications of urbanization for health and well-being remain unclear. Urban environments carry both benefits and risks . Urban uSLC6A4 increases susceptibility to depression in adults exposed to stress during early development [Environmental factors likely influence heritable complex human traits, from temperament and cognition to psychiatric illness risk –16. For elopment . In addielopment . Neuroimelopment . Using felopment . The samelopment  and to delopment . In the elopment –24. Hereelopment .COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2), specifically polymorphisms COMT rs4680 , DRD1 rs4532 (-48 A/G dDel), and DRD2 rs1076560. Prior reports and a meta-analysis have linked COMT Val158Met (rs4680) to DLPFC fMRI activation [DRD1 and DRD2 influence cortical DA synaptic activity and neuronal tuning [DRD1 rs4532 is in strong LD across the gene and DRD1 binding has been tied to fMRI memory tasks [DRD1 rs4532 allele has been associated with fMRI measures of working memory tied to prefrontal activation and illnesses like schizophrenia [DRD2 rs1076560 minor allele carriers showed altered fMRI activation during our N-back WM task [In addition to fMRI effects of urbanicity, we sought GxE interaction between urbanicity and dopamine genes. Dopamine genes represent critical links to cortical dopamine and its fundamental role in DLPFC function with ties to our fMRI phenotype. Additionally, stress affects dopamine –26, and tivation . DRD1 anl tuning –39. DRD1ry tasks –41. The ophrenia –43. DRD2 WM task –46.COMT, DRD1, and DRD2 polymorphisms via interaction. Based on prior associations between urban rearing and altered fMRI activation, we tested for the influence of childhood urbanicity and urbanicity-dopamine gene interactions using fMRI measures. Specifically, the N-back fMRI WM challenge known to activate a network including dorsolateral prefrontal cortex (DLPFC) [Given the importance of dopamine for optimal prefrontal function, we hypothesized that a main effect of childhood urbanicity would modulate the influence of  (DLPFC) –48 was uCOMT discovery sample, 124 unrelated Caucasian healthy volunteers between the ages of 18 and 55 (‘discovery’)  were studied  from our ongoing study  combined from the discovery and US replication samples  with approval of the National Institutes of Health Committee for the Scientific Review of Protocols (CSRP) and the Combined Neurosciences IRB (CNS IRB). The local Institutional Review Board  approved the Italian study. After complete description of the protocol and procedures, all participants gave written informed consent in accordance with the Helsinki Declaration.COMT rs4680, DRD1 rs4532, and DRD2 rs1076560 single nucleotide polymorphisms (SNPs) using the 5′ exonuclease TaqMan® assay and direct sequencing . SNP probe and primer sets were acquired as ‘Assays on Demand’ from Applied Biosystems using DNA extracted from transformed B lymphocyte cell lines using standard procedures [DRD2 rs1076560, minor allele homozygotes and heterozygotes were collapsed. Occult differences in ancestry or genetic stratification could theoretically confound the findings since no single polymorphism acts alone independent of genetic background. Thus, stratification based on urbanicity  was tested in the US samples for whom we had genome-wide variation data based on Illumina 550k SNP chip genotypes. PLINK [Subjects were genotyped for the ocedures . Additios. PLINK  was useds. PLINK   signal data were acquired with fMRI during a WM N-back paradigm that generates a heritable prefrontal phenotype –61. NumbCOMT replication, the Italian COMT, and DRD1/DRD2 samples, fMRI data acquisition and analysis were perfomed in the same way as for the COMT discovery sample. The data were corrected for head motion artifacts, with six motion parameters  and three rotational ) used as covariates of no interest in first level analyses. The fMRI data were then anatomically normalized into a standard space Montreal Neurological Institute (MNI) template [Whole-brain BOLD fMRI data were acquired at 3Tesla  using gradient-echo echo planar imaging  . The fMRtemplate .DRD1 and DRD2, we also analysed these data in the same fashion. To illustrate the COMT replication results in terms of anatomical overlap with the results from the discovery COMT-by-urbanicity interaction, regions of interest were defined from the discovery results and then applied to each replication’s activation maps using MRIcron [For first level analyses, the average BOLD signal from the 2-back task was contrasted with the signal from the 0-back task for each subject in order to identify the brain regions activated during the WM aspect of the task. The timings used for each of the blocks (2-back and 0-back) were from the task output, and the BOLD signal during these blocks of time was then contrasted between the 2-back and 0-back conditions. At the second level, multiple regression analyses were used to determine main effects of childhood urbanicity, dopamine genotype, as well as GxE interaction effects (dopamine gene-by-urbanicity) in one multiple regression using these three factors. These analyses were whole brain, but we report only DLPFC results as this was our primary hypothesized region for these tests. Post hoc SPM ANOVAs were performed in the discovery sample to confirm that each subgroup used in the multiple regression significantly differed from each other in the same direction found in the multiple regression—i.e., urban showed significantly greater fMRI activation than town, the latter significantly greater than rural. Sex and age were used as covariates of no interest in all analyses. For the US discovery, US replication, and the Italian replication samples, we performed the same fMRI data acquisition and analysis. Combining US discovery and US replication samples for  MRIcron –67 at a http://neurosynth.org/). Neurosynth meta-analyses are easily searchable for the papers contributing to any given meta-analysis and surfable using a 3-D graphical depiction of significant results within brain . We created our ROIs using meta-analytically derived activation in Neurosynth . NeurosyCOMT discovery sample were performed to address confounding effects of current urbanicity. If individuals had moved to another urbanicity category after childhood, then the childhood measures could have represented current urbanicity (urban environment at the time of study). We investigated this possibility in two ways. First, we repeated the analyses substituting current urbanicity for childhood urbanicity and using only subjects who had changed urbanicity categories. Second, we calculated the difference between childhood and current urbanicity and added this change in urbanicity into the multiple regression design. Next, given evidence elsewhere of a potential interaction between COMT and sex [COMT discovery results depended upon smaller subsamples subsumed in the multiple regression analyses at discovery and collapsed to a two-sample t test.We also tested for differences between urbanicity groups in age, education, socioeconomic status (SES) , IQ, han and sex –76, all COMT, DRD1, or DRD2 genotype or urbanicity groups (COMT discovery sample using the same multiple regression approach plus years of education as a covariate of no interest did not change the results significantly. Even though no childhood socioeconomic status (SES) differences were found, we nonetheless repeated the analysis of the discovery cohort using current and childhood SES measures as covariates of no interest and found the results unchanged. In the COMT US replication, no demographic differences were found across genotype groups. In the COMT Italian replication, a difference was found in childhood SES. Therefore, we added childhood SES as a covariate of no interest to the Italian analysis, which did not significantly change the results. For the DRD1/DRD2 cohort, there was a difference across groups for years of education (p = 0.02). An analysis including education as a covariate of no interest did not significantly change the results for either DRD1 or DRD2. Participants were primarily right handed, and handedness did not significantly differ between urbanicity groups in the discovery, US and Italian replications, nor DRD1/DRD2 samples . For DRD1 and DRD2 (n = 253), no differences in genotype frequencies for DRD1 rs4532 (Chi square p = 0.89) or DRD2 rs1076560 (Chi square p = 0.72) were found. Using the COMT discovery sample, no evidence was found for stratification across childhood urbanicity via IBS measures. No evidence for clustering based on urbanicity nor indication of significant heterogeneity was found either. Permutation testing for urbanicity-related IBS differences was not significant . We also failed to detect evidence for ancestry differences based on significance testing using the means and standard deviations  and scatterplots of the first nine components from probabilistic principal component analysis showed no apparent outliers enriched in either urban or rural samples  or in the Italian sample (p = 0.9). A trend for genotype frequency differences in the U.S. replication sample (p = 0.06) was found, but no overall genotype frequency differences in COMT discovery sample, those growing up exclusively in an urban setting (n = 28) were inefficient—defined as more BOLD activation for equivalent task performance—relative to those raised in rural (n = 30) or town (n = 66) environments  were relatively inefficient compared to Val/Val subjects , approaching but not meeting COMT meta-analytical results reported elsewhere (d = 0.73–0.91) [COMT-urbanicity interaction, effect sizes were also moderate (d = 0.47–0.60) and (d = 0.51–0.63), respectively). We also calculated effect sizes for the two replication samples. In the US replication sample, moderate effect sizes were found for COMT (d = 0.46–063), urbanicity (d = 0.58–0.79), and the COMT-urbanicity interaction (d = 0.50–0.78). Effect sizes were smaller for the Italian replication sample—COMT (d = 0.22–0.32), urbanicity (d = 0.24–033), and the COMT-urbanicity interaction (d = 0.30–0.38).Moderate effect sizes for the typical 73–0.91) . For botDRD1 and DRD2  showing an alteration of the genotype effect for urban subjects. DRD2-urbanicity interactions were found in left DLPFC . Similar to the COMT interaction, moderate effect sizes for DRD1-by-urbanicity and DRD2-by-urbanicity were found .The small cell sizes in the analyses were for urban Val/Val (n = 5) and rural Val/Val (n = 2) in the discovery sample and rural Met/Met (n = 2) in the Italian replication sample. When we estimated effects ‘as if’ the COMT discovery results depended upon smaller subsample, we found effects in the small cohort similar to those found in the overall analyses for the COMT and childhood urbanicity on prefrontal activation, which replicated in two additional samples. Two other dopamine genes, DRD1 and DRD2, were found to interact with urbanicity as well. Taken together, these results show how one’s environment during childhood can impact adult brain function, and specifically in relation to altering effects of dopamine genes.This is a novel study in that it replicated a GxE interaction found using functional neuroimaging. The findings showed an interaction between COMT, the GxE involved a well-characterized and ‘human-specific’ genetic polymorphism  using a heritable fMRI measure of working memory-related prefrontal information processing. Additionally, findings in the COMT replication samples overlapped anatomically with the discovery sample. We believe starting at any of the three COMT samples would have the same replication outcome. Importantly, childhood urbanicity and the GxE effects were similar for urban environments in different countries. In the initial discovery sample, no evidence was found for significant demographic or genetic confounds—neither differences in SES nor evidence of whole genome based stratification. There were no effects of adult or current urbanicity. Applicable to all dopamine gene genotype-phenotype effects, it is important to note that WM performance did not differ across groups and thus relative differences in activation should not have been affected by behavioral effects.In the case of DRD1 and DRD2 were also found in the prefrontal cortex, suggesting that childhood urbanicity and GxE effects extend to other genes in the dopamine pathway. Analyses of the dopamine receptor genes DRD1 and DRD2 revealed GxE interactions with urbanicity (GxE). Although we did not have replication samples for DRD1 and DRD2 analyses, their effect sizes were also moderate. We conclude that an urban childhood has an effect on brain function as measured with fMRI during WM that persists into adulthood. Specifically, urban upbringing altered the relationship between fMRI activation and polymorphisms in COMT, DRD1, and DRD2. In terms of urban upbringing, these dopamine findings are evolutionarily interesting considering that dopamine mutations likely predate modern civilization and the emergence of large cities [Interactions between childhood urbanicity and e cities .We speculate that the interaction with dopamine genes involves environmental changes in cortical dopamine availability. Dopamine sensitization or altered release of dopamine by environmental stress , 30, 78—COMT, DRD1, and DRD2 are potentially involved in both baseline state and stimulated dopamine effects, suggesting the potential for multiple routes to suboptimal DLPFC function in the urban-reared. As a functional coding variant, COMT rs4680 effects on DLPFC activation reflect the decreased synaptic dopamine conferred by the more active COMT Val-associated catabolic enzyme. The shift towards suboptimal performance in the urban-reared Met-carriers fits nicely with dopamine sensitization wherein increased dopamine release in response to stress coupled with greater synaptic dopamine released by stressors, potentially like urban environments, would move urban Met-carriers beyond optimal dopamine. Such COMT changes relate directly to DLPFC dopamine levels, but the contribution of DRD1 and DRD2 polymorphisms are somewhat less clear.Dopamine regulation for optimal working memory performance is dependent on both baseline dopamine state as well as dopamine effects with cognitive load . The relCOMT rs4680 and D1 receptors [DRD1 rs4532 is in the 5’-untranslated region of this gene and has a relationship to DRD1 expression [DRD1 as it has been associated with dopamine-associated conditions including tardive dyskinesia in schizophrenia [D1 (dopamine receptor 1) is more abundant in DLPFC than D2 (dopamine receptor 2) and has been closely tied to working memory deficits. The neuropsychiatric disorder most affected by childhood urbanicity, schizophrenia, has been shown via PET imaging of D1 ligand binding to have altered DLPFC D1 receptor abundance. PET studies have shown something of the relationship between eceptors . Slifsteeceptors . DRD1 rspression . This SNophrenia , attentiophrenia , and resophrenia .DRD2 allele variation making cortically-centered changes more likely in this case. The DRD2 intronic SNP rs1076560 alters the relative expression of D2 short and long isoforms (D2S and D2L)—increasing the D2S/D2L ratio and generating optimal D2 regulation in DLPFC [DRD2-urbanicity interaction. DRD1 and DRD2 influence cortical DA synaptic activity and neuronal tuning and are tied to prefrontal cognitive functioning and memory performance, particularly D1 [DRD2 has been associated with schizophrenia in a recent genome-wide association study [D2 receptors are more heavily expressed in the striatum but have associated function pre- and post-synaptically within prefrontal cortex—for example as an autoreceptor whose altered abundance could further negatively impact cortical dopamine. Any changes in D2 receptors could have altered striatal communication with or reciprocal regulation of DLPFC. However, we did not find any striatal changes associated with in DLPFC –that coularly D1 –45. Thislarly D1 ; therefolarly D1 –90. In fon study . AlteratCOMT Val allele appear sensitive to stress-related methylation that negatively influences prefrontal efficiency [A limitation in investigations such as ours is that urbanicity, as defined by population size, represents a nonspecific factor with effects that could be multi-determined and potentially modified by other influences such as SES and cultural perspectives. However, risk for schizophrenia based on urbanicity is not explained by other factors that could be associated with city living, including childhood infection, household crowding, obstetric complications, or SES , 92–94. ficiency . As deveCOMT, nor did the addition of an additive term significantly alter the analysis. While a previous study found no association between urbanicity and activation during the N-back task, those negative results in a much smaller study only applied to activation within amygdala and cingulate regions and not to activation within DLPFC [In comparison to the sample sizes used to explore genome-wide genotype effects, our large-for-neuroimaging samples would be small. Our thresholds without whole brain correction may have introduced false positives. However, the multiple replications across three samples and three dopamine genes using the significance thresholds as at discovery help to mitigate this concern. Effect sizes for all cohorts suggest our numbers were adequate. Our 5-year interval measure differs from the more common ‘urbanicity-by-year’ methods and could have made our analyses less sensitive to main and interactive effects. Repeating our analyses using years of residence and their urbanicity yielded the same results as our initial analyses. Gene-environment interactions are not necessarily multiplicative, but we did not detect a significant additive interaction between urbanicity and in DLPFC .COMT and across three dopamine genes , the data strongly suggest a lasting impact of an urban upbringing on aspects of DLPFC function as measured by fMRI, additionally altering the relationship with genetic background and potentially other critical aspects of brain function.Based on these and other data, urbanicity is linked to quantifiable complex brain function, here working memory, that could generate novel insights for genetic studies of cognition and mental illness. Our findings concerned healthy people, but future work could extend into those neuropsychiatric populations known to have increased risk from urban living. Across three datasets and two countries for S1 FilePanel A. U.S. Replication Demographic Characteristics and Working Memory Performance. Demographic differences across urbanicity categories in the US replication sample. Significant differences are denoted by p values. Abbreviations: SES = socioeconomic status, WAIS-IQ = Wechsler Adult Intelligence Scale—Intelligence Quotient, RT = reaction time, n.s. = non-significant. Panel B. Italian Replication Demographic Characteristics and Working Memory Performance. Demographic differences across urbanicity categories in the Italian replication sample. Significant differences are denoted by p values. Abbreviations: SES = socioeconomic status, WAIS-IQ = Wechsler Adult Intelligence Scale—Intelligence Quotient, RT = reaction time, n.s. = non-significant. Panel C. DRD1 and DRD2 Demographic Characteristics and Working Memory Performance. Demographic differences across urbanicity categories for DRD1 and DRD2 (both n = 253). Significant differences are denoted by p values. Abbreviations: SES = socioeconomic status, WAIS-IQ = Wechsler Adult Intelligence Scale—Intelligence Quotient, RT = reaction time, n.s. = non-significant. DRD1 and DRD2.Panel D. Main Effect of  Coordinates are in MNI space with Brodmann areas (BA) indicated in parentheses. Abbreviations: L = left, R = right, MNI = Montreal Neurological Institute coordinates, SVC-FWE = small volume correction using family-wise error. DRD1- and DRD2-by-Urbanicity Interaction.Panel E. DLPFC Activation for  Coordinates are in MNI space with Brodmann areas (BA) indicated in parentheses. Abbreviations: L = left, R = right, MNI = Montreal Neurological Institute coordinates, SVC-FWE = small volume correction using family-wise error. Panel F. Neurosynth coordinates for creating regions of interest. Activation coordinates and corresponding Neurosynth ROI foci used for small volume correction using family-wise error (SVC-FWE). Coordinates are in MNI  space. Panel G. Absence of genetic stratification by urbanicity. Exploration of differences in genetic stratification using genome-wide SNP genotypes via both multidimensional scaling (MDS) in PLINK [Panel H. Use of Neurosynth to create regions of interest. Small volume corrections were based on maxima identified using meta-analysis in Neurosynth [http://neurosynth.org/analyses/terms/). Studies for Neurosynth meta-analysis were gathered and analyzed using the search terms ‘working memory.’ The cross-hairs are centered within a maxima from left dorsolateral prefrontal cortex used to create a spherical ROI to correct local statistical maxima in each of three analyses for the COMT-urbanicity interactions and two analyses for DRD1- and DRD2-urbanicity interactions. This maxima had a z-score = 6.67 with the overall image was thresholded at z-score > 5 for display purposes. Abbreviations: XYZ = coordinates in MNI standard space, D = dorsal, V = ventral, A = anterior, P = posterior, L = left, R = right.in PLINK  and probin PLINK . Scatterurosynth  (http://(DOCX)Click here for additional data file.


Mycobacterium bovis (Mbovis) infection than other domestic ruminants such as cattle and goats. However, there is increasing evidence for the role of this species as a domestic Mbovis reservoir, mostly when sheep share grazing fields with infected cattle and goats. Nevertheless, there is a lack of information about the pathogenesis and the immune response of Mbovis infection in sheep. The goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response. Samples from bronchial lymph nodes from twelve Mbovis-naturally infected sheep were used. Four immunohistochemical protocols for the specific detection of T-lymphocytes, B-lymphocytes, plasma cells and macrophages were performed to study the local immune reaction within the granulomas.Sheep have been traditionally considered as less susceptible to Differences were observed in the predominant cell type present in each type of granuloma, as well as differences and similarities with the development of tuberculous granulomas in other species. Very low numbers of T-lymphocytes were observed in all granuloma types indicating that specific cellular immune response mediated by T-cells might not be of much importance in sheep in the early stages of infection, when macrophages are the predominant cell type within lesions. Plasma cells and mainly B lymphocytes increased considerably as the granuloma developed being attracted to the lesions in a shift towards a Th2 response against the increasing amounts of mycobacteria. Therefore, we have proposed that the granulomas could be defined as initial, developed and terminal.Results showed that the study of the lymphoid tissue granulomata reinforces the view that the three different types of granuloma represent stages of lesion progression and suggest an explanation to the higher resistance of sheep based on a higher effective innate immune response to control tuberculosis infection. Mycobacterium tuberculosis complex (MTBC), can be part of the multi-species system which can maintain tuberculosis (TB) in a region, at least in mixed farms where sheep share grazing fields with Mycobacterium bovis (Mbovis)-infected cattle and goats [Recent studies have shown that sheep, traditionally considered a rare host for the nd goats . Microscnd goats , althougnd goats –4.Granulomas are observed in active, latent and reactivation stages of TB. The TB lesion is highly dynamic and shaped both by the pathogen and the host defense elements . In humaTo gain further insight into the knowledge of the immunopathology of tuberculous lesions in sheep, the goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response.A total of 12 sheep naturally infected with Mbovis (spolygotype SB0886) from the Galicia region (Northwestern Spain) were selected from a previous study [Twelve sheep showing granulomas only in bronchial lymph nodes were selected, four sheep with granuloma type I, four with granuloma type II and four with granuloma type III. We choose the bronchial lymph nodes because they were the most frequently affected tissues . They we2O2 for 10 min at room temperature (RT) and washed with water for 10 min. Then, epitope demasking techniques  and no differences were observed between them.Significant differences in the numbers of cell types were observed in each TB granuloma type Table .Table 2CIHC analysis for CD3 showed very few scattered positively stained lymphocytes within type I and type II granulomas Table  and 2, rB cells were found in all granulomas, mainly in type III granulomas, forming clusters surrounding the necrotic area Fig. . In typeMacrophages were the predominant cells observed within granulomas of the types I and II Figs.  and 2. HNo cells immunostained for lambda chains were observed in type I granuloma Fig. . A few sp < 0.0001), but not for T lymphocytes and macrophages , developed (type II) and terminal (type III). Initial granuloma would represent an initial or latent stage, developed granuloma a more mature stage and terminal granuloma a regressive stage, associated with mineralization and fibrosis indicative of resolution.Therefore according to their cell composition we defined tuberculous granulomas as This preliminary study describes, for the first time, the distribution of T cells, B cells, macrophages and plasma cells in tuberculous granulomas from sheep naturally infected with Mbovis. Differences were observed in the predominant cell type present in each type of granuloma, as well as differences and similarities with the development of tuberculous granulomas in other species –10.It is important to note the scarce presence of T lymphocytes in all granuloma types < 10 cells), which would suggest a clear difference with the spectrum of lesions of TB in other species, such as cattle, where T lymphocytes are essential in the initial cellular immune response against Mbovis , 7. In t cells, wThe number of B lymphocytes increased considerably as the granuloma developed. In terminal granulomas, the amount of macrophages decreased while B-lymphocytes increased, suggesting a humoral-mediated immune response. A calcified granuloma  generally represents a successful immune response and is associated with fewer inflammatory cells than other granulomas . In the M. caprae showed that the volume of gross pulmonary lesions, quantified by computed tomography and bacterial load in respiratory lymph nodes were similar to those observed in goats experimentally challenged with M. caprae at a similar dose suggesting that the susceptibility of sheep to TB infection is similar to that observed in goats [Lambs subjected to experimental challenge with in goats . In the in goats . This fiin goats , 17 but In conclusion the three types of granulomas described could be the result of different combinations of the three immune response routes: innate, adaptive cellular and adaptive humoral . Thus in


The precursors were electrospun directly onto the fluorine-doped tin oxide (FTO) glass. The heating rate and FTO as substrate play key roles on preparing porous hollow nanofiber. As cathode materials for lithium-ion batteries (LIBs), LiMn2O4 hollow nanofibers showed the high specific capacity of 125.9 mAh/g at 0.1 C and a stable cycling performance, 105.2 mAh/g after 400 cycles. This unique structure could relieve the structure expansion effectively and provide more reaction sites as well as shorten the diffusion path for Li+ for improving electrochemical performance for LIBs.The LiMn To iatteries –7. Amongl oxides , 9. Wang0 cycles , 13.The cathode materials with special structure and morphology could increase their specific capacity and cycling performance, aiming to overcome the mechanical strain arising from the huge volume variation and the particle agglomerations during the charge/discharge processes of lithium-ion battery, which results in the increased diffusion lengths and serious electrical disconnection , 14, 15.2O4 nanofiber with porous hollow structure and morphology has been successfully synthesized by modified electrospinning method. It is discussed that the effects of varied heat treatment factors in detail which explore the formation mechanism of nanofibers with a hollow structure. Furthermore, the electrochemical performances of the samples as cathode for LIBs were evaluated. It is worth that LiMn2O4 porous hollow nanofiber morphology delivers the higher electrochemical performance.In this work, LiMn2O4 nanofiber with porous hollow structure and morphology has been successfully synthesized by modified electrospinning method. All chemicals were of analytical grade and used as purchased without further purification. Firstly, the precursor solution was prepared by mixing 2 g of polyvinylpyrrolidone  in 20 ml ethanol under vigorous stirring for 4 h. 1.224 g Li(CH3COO) · 2H2O and 5.88 g Mn(CH3COO)2 · 4H2O were dissolved into the solution. And the acetic acid (1 ml) was then added to the above solution under continuous stirring for 2 h. After that, the precursor solution was transferred into a syringe with the metal syringe needle. The 20 kV high voltage was applied across the collector ) and metal needle, whose distance maintained at 20 cm. The precursor collected on collectors was dried at 60 °C for 1 h. LiMn2O4 cathode was obtained by calcining the precursor nanofibers in air under different heating rates and temperatures.The LiMn2 adsorption-desorption surface area measurements were conducted on a volumetric sorption analyzer .The X-ray diffraction patterns (XRD) of fabricated powders were recorded by a Rigaku D/max 2500 pc X-ray diffractometer with Cu K radiation (=1.54156 Å) at a scan rate of 5 deg/s. The field emission scanning electron microscope (FESEM) was conducted on a JEOL JSM-6700F field emission scanning electron microscopy. Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) observations were performed by a JEOL 2100F. The thermogravimetric (TG) curves were obtained by a Perkin-Elmer TGA 7 thermogravimetric analyzer from room temperature to 800 °C at a heating rate of 10 °C/min. Brunauer-Emmett-Teller (BET) N2O4 nanofiber with porous hollow structure for the working electrode, which prepared by casting slurry containing 10% acetylene black, 10% polyvinylidene fluoride (PVDF), and 80% active material onto a aluminum foil, were performed via CR2025-type coin cells assembled in a dry argon-filled glove box. The test cell was assembled using working electrode and lithium foil which were separated by a Celgard 2400 microporous membrane. The electrolyte solution was prepared by dissolving 1 M LiPF6 in ethyl carbonate and diethyl carbonate (1:1 by volume). Galvanostatic charge-discharge cycling tests were performed using a LAND CT2001A multi-channel battery testing system in the voltage range between 3.0 and 4.4 V at room temperature.The electrochemical experiments of LiMn2O4 nanofibers annealed at 700 °C for 5 h with a heating rate of 5 °C/min, respectively. Figure 2O4 particles is almost in accordance with the d-spacing value (4.76 Å) of cubic LiMn2O4 in (111) plane. And the regular lattice fringes can also demonstrate the high crystallinity [Figure allinity , 23. FigMn2O4 in 11 plane.allinity .Fig. 1a2O4 nanoparticles calcined at 650 °C and 5 °C/min, the particles with heterogeneous size could be prepared, without nanofibers. Figure 2O4 nanofibers calcined at different temperatures. As it can be seen from Fig. 2O4 phase (JCPDS 88-1749) with no other impurities. Meanwhile, the sharpness of the X-ray diffraction peaks confirms that the material should be crystallized LiMn2O4. However, some peaks which belong to Mn2O3 phase are also can be seen in the nanofibers obtained at 650 °C, which is evident that the presence of unavoidable impurity phase (Mn2O3) is can be seen when the as-spun LiMn2O4 nanofibers are treated at a temperature of 650 °C [2O4 nanofibers without any other impurities could be synthesized at 700 °C.Figure f 650 °C . The cal2 and H2O are slower, so the LiMn2O4 particles formed earlier have more time to grow. Following it, the size of nanoparticles is larger and the morphologies of the samples are bending and rough because of the quickly decomposition of polymer and growth of crystal. It is shown that the morphology of porous surface is affected by the higher release of CO2 and H2O with the higher heating rate. In addition, the porous hollow nanofibers could be more synthesis on FTO as substrate. The agglomeration of nanofibers is much more serious with Al foil as substrate in Fig. 2O4 porous hollow nanofibers by electrospinning it onto FTO glass directly to form porous electrode.To understand the formation mechanism of the porous hollow nanofibers structure, the as-prepared samples were analyzed by FESEM at different heating rates  with different substrates such as Al foil  and FTO  in Fig. 2O and CO2 and releases, meanwhile the inner organic moieties together with metal ions present in the precursor move toward the outer wall under the effect of concentration difference [+ and Mn2+ aggregated react with each other in the air atmosphere resulting in the formation of LiMn2O4, which continues to grow and interconnects to form the final continuous tubular structure with porous and thin wall [The formation of the hollow nanofibers with porous structure is introduced in Fig. fference . In thathin wall , 28. The2 adsorption-desorption and the corresponding pore size distribution curve of S1, S2, and S3 LiMn2O4 nanofibers  are shown in Fig. 2 adsorption and desorption isotherms in the P/P0 ranging from 0.7 to 1. It confirms the broad pore size distribution toward larger mesopores  were evaluated by galvanostatic charge/discharge cycling in the voltage range of 3.0–4.4 V at 0.1 C (1 C = 148 mAh/g). In Fig. + into or out LiMn2O4 during the charge and discharge process. The two flat voltage plateaus are corresponding to the two-phase and one-phase reaction modes, respectively, which are the region equilibrium between LiMn2O4 and Li0.5Mn2O4 phases (LiMn2O4⇋Li0.5Mn2O4 + 0.5Li++0.5e−) and the equilibrium between Li0.5Mn2O4 and γ-MnO2 (Li0.5Mn2O4⇋2MnO2 + 0.5Li++0.5e−) [2O4 porous hollow nanofibers, which shows the capacity remains of 105.2 mAh/g at 0.1 C after 400 cycles. As it can be seen from Fig. The electrochemical performances of the LiMn++0.5e−) . The ele++0.5e−) . After 12O4 hollow nanofibers. The LiMn2O4 electrode shows a capacity loss from 122 mAh/g at 0.1 C to 102 mAh/g at 1 C, which is only 16.3% of an initial discharge capacity at 0.1 C. Furthermore, after 80 cycles (from the 81st cycle to the 161st cycle), the discharge capacity of LiMn2O4 could be recovered (123 mAh/g), when the charge-discharge rates reduce from 1 C to 0.1 C. Figure 2O4 porous hollow nanofiber electrode delivers the excellent rate capability, especially for showing stable electrochemical property at different current densities.Figure 2O4 porous hollow nanofibers are due to the novel porous hollow structure. Firstly, the porous nanostructure can provide more reaction sites for the intercalation/deintercalation of Li+ and shorten the diffusion path for Li+, leading to the better rate capability [2O4 nanofibers as the cathode for LIBs.On the basis of the above results, the high reversible capacity, rate behavior, and excellent cycling life of the LiMnpability , 32. Sec2O4 hollow nanofibers with a porous structure have been synthesized by modified electrospinning techniques on the FTO substrate. And the precursor was calcined in air at 700 °C. As the cathode materials for LIBs, the LiMn2O4 with special morphology exhibits good cycle life and high capacity, which delivers a high specific capacity of 125.9 mAh/g and a stable cycling performance of 105.2 mAh/g after 400 cycles, at 0.1 C. It is certificated that the porous and hollow structure improves the utilization of the active mass and dual conduction of Li+ and electrons and effectively relieves the structural strain and volume change, which could enhance the cycling performance and rate stability for advanced energy storage devices.In summary, the LiMn


XRD, SEM, TEM, N2 adsorption-desorption, mass spectrometry, NMR and EDS results showed that the composite molecular sieve contained two pore channels. Py-FTIR results showed that the addition of HY molecular sieves improved the acidity of the composite zeolite. The crystallization mechanism during the growth of FAU/SBA-15 shell was deduced from the influence of crystallization time on the synthesis of FAU/SBA-15 core-shell structured composite molecular sieve. HY dissociated partially in H2SO4 solution, and consisted of secondary structural units. This framework structure was more stable than its presence in the isolated form on the same ring or in the absence of Al. Thus it played a guiding role and connected with SBA-15 closely through the Si-O bond. This resulted in the gradual covering of the exterior surface of FAU phase by SBA-15 molecular sieves. The presence of SBA-15 restricted the formation of the other high mass components and increased the selectivity towards ethylbenzene.Composite molecular sieves, FAU/SBA-15, having core-shell structure were synthesized. The synthesized composite sieves were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), pyrolysis fourier transform infrared (Py-FTIR) spectroscopy, temperature programmed desorption spectra (NH  HoweverRecent years have seen the emergence of a new type of composite molecular sieves with core–shell structure . The advSome methods can be used to synthesize core–shell composite molecular sieves . CompareComposite molecular sieves with core–shell microporous and mesoporous structure  showed gDetailed study on the synthesis of core–shell composite molecular sieves using the microporous molecular sieves Y, with high acidity and high catalytic activity, equivalent to that of ZSM, has been rarely reported. Therefore, in this work, a secondary method has been employed to synthesize FAU/SBA-15 type core–shell composite molecular sieves, to extend the types of core–shell composite molecular sieves and their applications in the macromolecular catalysis. The crystallization mechanism of the shell growth in Y/SBA-15 was deduced, based on the characterization results. Moreover, its effect on the catalytic cracking of polystyrene has also been investigated.2.2.1.2SO4), sodium silicate (water glass), and tetraethyl orthosilicate (TEOS)  were procured from Shenyang Chemical Reagent Factory. (PEO20-PPO70-PEO20) block copolymer (P123) was obtained from Sigma-Aldrich Shanghai. N-hexane  was purchased from Shenyang Chemical Reagent Factory, whereas polystyrene (PS) particles were purchased from Fushun Catalyst Factory.Sulfuric acid  solution into the fully dissolved sodium aluminate solution, and make the molar composition of the whole: 16 Na2O:Al2O3:10 SiO2:180 H2O. After some further stirring, crystallize the mixture in stainless steel crystallization kettle at 90 °C. Filter and wash at 110 °C, and the NaY-type molecular sieves were obtained after drying. The ratio of Si to Al of NaY was 2.44, which was determined by X-ray fluorescence spectroscopy (XRF) ; the Doctoral Program of Higher Education by Chinese Education Department [grant number 20100042110008]; Liaoning BaiQianWan Talents Program, and the Talent Scientific Research Fund of LSHU [grant number 2016XJJ-064].


The dopamine hypothesis of schizophrenia has been extensively proposed as a neurobiological mechanism that explains the relationship between schizophrenic symptoms and hyperdopaminergic states. This hypothesis is supported by direct and indirect evidence, and it mainly postulates that antipsychotics act blocking dopamine receptors. When focusing on delusional disorder patients, especially delusional disorder somatic type, a great effort towards the search for a biological basis of treatment response has been recently demonstrated. Thus, the main goal of this systematic review was to examine the evidence explaining the biological underpinnings of treatment response in delusional disorder.A systematic review was performed using Pubmed, Scopus and PsycINFO databases (from 1990 to October 2017), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The following search terms were used: [(‘treat*’ OR ‘therap*’ OR ‘biol*’) AND ]. This systematic computerized search was completed by additional studies hand-checked through reference lists from the included studies and review articles. Studies were only included if the met our inclusion criteria: (a) the International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis for delusional disorder, (b) be published in peer-reviewed journals, (c) in English, German or Spanish, (d) and reporting a hypothesis for the biological basis of treatment response in delusional disorder, irrespective of method and study design. Exclusion criteria were: (a) studies including organic delusional disorder or (b) somatic delusions secondary to other psychiatric diagnoses. The literature search strategy, data extraction and synthesis was conducted independently by two authors . When disagreement, it was solved by consensus.A total of 59 articles were identified, of which 12 met our inclusion criteria. Four hypotheses were addressed: (1) Dopaminergic dysfunction (n=4): ziprasidone-induced supersensitivity psychosis by chronic blockade of D2 Dopamine Receptor (DRD2) (n=1); pretreatment levels of plasma homovallinic acid (pHVA) (n=1); dopamine transporter (DAT) dysfunction (n=1) and effectiveness of aripiprazole (DRD2 agonist) (n=1). (2) Serotonergic dysfunction (n=6): drug occupancy in 5-HT1A and 5-HT2A receptors (n=3) and efficacy of 5-HT2 antagonists (n=3). Brain dysfunction (n=7): hypoperfusion in cerebral blood flow in temporal and parietal lobes, left side (n=5), right side (n=1) and lack of basal ganglia and subcortical gray matter lesions (n=1). Genetic evidence (n=1): implications of DRD2 Ser311Cys, DRD3 Ser9Gly and TH VNTR polymorphisms.The strongests biological contributors for treatment response in delusional disorder seem to be those implicating monoaminergic systems, particularly dopamine and serotonergic neurotransmitters. Although the low level of evidence, the serotonergic dysfunction may be associated with response rates, especially in delusional disorder somatic type. The link between genetic variants of dopamine receptors and neuroimaging findings in delusional disorder may open new avenues for the search of the biological underpinnings of treatment response. The evidence for an integrated model involving dopamine and serotonin systems bears further investigations.


Further results on the adsorption performance of Pd(II) IIPs on Pd(II) confirmed 4-VP was the most promising candidate for the synthesis of Pd(II) IIPs with an adsorption capacity of 5.042 mg/g as compared with ANA and AAA. The influence of operating parameters on Pd(II) IIP’s performance on Pd(II) adsorption was investigated. There was an increase in the adsorption capacity of Pd(II) IIPs at higher pH, temperature, and initial concentration of Pd(II). The results of multi-metal competitive adsorption experiments showed that Pd(II) IIPs had selectivity for Pd(II). An adsorption equilibrium could be reached at 180 min. Kinetic analysis showed that the adsorption test data fitted best to the pseudo-second order kinetic model, and the theoretical equilibrium adsorption capacity was about 5.085 mg/g. The adsorption isotherms of Pd(II) by Pd(II) IIPs agreed well with the Freundlich equation, suggesting a favorable adsorption reaction under optimal conditions. These results showed that Pd(II) IIPs have potential application in the removal of Pd(II) from aqueous solutions and may provide some information for the selection of functional monomers in the preparation of Pd(II) IIPs.Three kinds of functional monomers, 4-vinylpridine(4-VP), 2-nicotinic acid(ANA), and 2-Acetamidoacrylic acid(AAA), were used to synthetize palladium(II) ion-imprinted polymeric nanospheres (Pd(II) IIPs) via precipitation-polymerization method in order to study the effects of different functional monomers on the adsorption properties of ion-imprinted materials. The results of UV spectra in order to study the interaction between template ion PdCl Palladium with unique physical and chemical properties is widely used in electroplating materials, catalysts, dental alloy, and brazing alloy , 2. WithIon-imprinted polymeric nanospheres with high selectivity for the separation of metals from aqueous solution compared with other common adsorbents has become one of the research hotspots in recent years –23. In t42− and functional monomer was analyzed by UV full wavelength scanning. Then, the best functional monomer was selected by comparing the adsorption effect of Pd(II) IIPs corresponding to three functional monomers on palladium(II). Through batch adsorption experiments, the adsorption performance of Pd(II) IIPs for palladium(II) ions in aqueous solutions was evaluated. Various characterization means of FTIR, SEM, and TGA were utilized to further explore the corresponding mechanism of Pd(II) adsorption onto Pd(II) IIPs.Many studies used 4-VP as the functional monomer in the preparation of Pd(II) IIPs, while few studies have involved the comparison of 4-VP with other functional monomers –30. In t2PdCl4, 4-vinyl pyridine , 2-allyl sulfhydryl nicotinic acid , 2-acetamidoacrylic acid , and ethylene glycol dimethacrylate  were purchased from Alfa company in the USA. Azo isobutyronitrile  was purchased from Shanghai zhongfugang Co. Ltd. Palladium single element standard solution was purchased from Chinese national standard material network. All chemicals were in analytical reagent grades and used without further modification. Ultrapure water was used to prepare all the solutions. All of the glassware was cleaned and rinsed with Milli-Q water and then dried in an oven overnight before using.The following chemicals K42−), functional monomers  and cross-linking monomer at 1:4:40. In the polymerization procedure, ethylene glycoldimethacrylate (EGDMA) was used as the cross-linking monomer, the polymerization mixture also included 2,2-azobisisobutyronitrile  and methanol (Porogen). The detailed operation is as follows:The palladium(II) ion-imprinted polymeric nanospheres were synthesized by precipitation-polymerization method. In the precipitation procedure, Pd(II) IIPs were prepared according to the ratio of template  methanol/water to remove the unreacted materials, and then palladium ions (PdCl42−) was leached from the polymer material by stirring with 4 × 50 ml of 1:1 HCl for 24 h until the washing solution was free from palladium ions. Finally, it was washed with deionized water until it reached a neutral pH. The polymers were dried under vacuum in a desiccator. In the same way, the non-imprinted polymers (NIPs) were prepared but without doping palladium ions.Firstly, 0.1 mmol K42− and functional monomer. Field-emission scanning electron microscope  was used to observe the morphology changes of ion-imprinted polymer before and after elution and non-ion-imprinted polymer. Fourier transform infrared (FTIR) spectra of the Pd(II) IIPs before and after elution, and NIPs were analyzed with FTIR Spectrometer  with KBr pellets in the range of 4000~400 cm−1. Brunauer, Emmett, Teller’s test  was used to analyze the specific surface area. Thermogravimetry analysis (TGA) was performed using Netzsch STA-409PC (Germany) from 313 to 873 K under a dried nitrogen atmosphere, and the heating rate was 10 K/min.Ultraviolet visible spectrophotometer  was used to analyze the interaction between PdClThe concentration of Pd(II) was determined by flame atomic absorption spectrophotometry . All batch adsorption experiments were performed using a thermostatic oscillator at 180 rpm with 10 mg adsorbent in a 50 mL plastic centrifuge tube containing 10 mL metal solution. Samples were taken in triplicate for all batch experiments. The effect of temperature on the adsorption of Pd(II) onto Pd(II) IIPs was evaluated at 15, 25, 35, 45, and 55 °C. Four interfering metal ions include Pt(II), Zn(II), Cu(II), and Ni(II) with an initial concentration of 10 mg/L were chosen to study the effect of multiple metals on adsorption of Pd(II).Isotherm adsorption experiments were carried out with a constant dosage of adsorbents and varying concentration of Pd(II) in the range of 1~80 mg/L at 25 °C (pH 2). Adsorption kinetic experiments were conducted by collecting solution at predetermined time intervals  and analyzing the final metal concentration in the aqueous solutions.r (%) is the removal efficiency of Pd(II), q (mg/g) is the capacity of Pd(II) adsorbed onto the adsorbent of Pd(II) IIPs, ce (mg/L) is the concentration of Pd(II) in solution at equilibrium, c0 (mg/L) is initial concentration of Pd(II) in solution, V (mL) is the volume of Pd(II) solution, and m (mg) is the mass of adsorbent.The percentage of Pd(II) removal and the adsorption capacity of the Pd(II) IIPs for Pd(II) ions can be calculated according to the following equations:qe is the amount of Pd(II) adsorbed on adsorbents at equilibrium (mg/g), qm is the theoretical maximum adsorption capacity of adsorbents under the certain conditions (mg/g), ce is the concentration of Pd(II) in aqueous solutions at equilibrium(mg/L), b is the Langmuir constant connected to the affinity between the Pd(II) and the adsorbents (L/mg), Kf is the Freundlich constant related to the adsorption capacity of adsorbents, and 1/n is the heterogeneity factor ranging from 0 to 1.The Langmuir Eq.  and Freuqe is the amount of Pd(II) adsorbed on adsorbents at equilibrium (mg/g), t is the contact time during adsorption process, qt is the amount of Pd(II) adsorbed on adsorbents at any time t (mg/g), k1 is the rate constant of the pseudo-first-order model (min−1), and k2 is the rate constant of the pseudo-second-order model (g/mg min).In order to further clarify the dynamics and rate-controlling mechanism for adsorption process, two commonly used kinetics models, i.e., the pseudo-first-order kinetics and the pseudo-second-order kinetics, were utilized to simulate the experimental adsorption data. The pseudo-first-order Eq.  and the 42− and 4-VP, and ANA and AAA in methanol before and after the interaction are shown in Fig. 42− has two absorption peaks at 219.4 and 242.4 nm, and the absorption peaks are shifted when different functional monomers are added. When functional monomer of 4-VP is dosed . It means that a kind of polymeric nanospheres Pd(II) IIPs with a larger surface area was produced after adding the imprinted ion. This observation can be interpreted by the significant differences in the spatial structure of Pd(II) IIPs and NIPs with the same kind of functional monomers. In the process of Pd(II) IIPs formation, due to the addition of imprinted Pd (II) ion, the functional monomer and the Pd(II) ion formed a coordination complex with the imprinting cavities, and the hole of the Pd(II) ion presents a “memory,” which leads to more adsorption amount of Pd(II) ions on Pd(II) IIPs than on NIPs. In addition, Table.In order to further study the adsorption effect of Pd(II) on Pd(II) IIPs and NIPs prepared by 4-VP, ANA, and AAA, the adsorption of Pd(II) on each materials was measured. As shown in Fig. By comparing the structure of these three kinds of functional monomers Fig.  and the The Pd(II) IIPs mentioned in the following studies were all prepared by using 4-VP as the functional monomer.2/g) was similar with the unleached Pd(II) IIPs (22.49m2/g), the little difference can be ignored, so it can be concluded that the elution has no effect on the morphology of the Pd(II) IIPs. The surface of the polymer becomes relatively rough after the addition of the PdCl42− template, which is due to the formation of imprinted holes. In comparison, the NIPs exhibit a smoother surface  ion-imprinted polymer.The microscopic morphology of leached Pd(II) IIPs, unleached Pd(II) IIPs and NIPs were observed. It can be seen from Fig. ace Fig.  with a mDifferent decomposition behavior can be observed from the thermogravimetric curves of unleached Pd(II) IIPs, leached Pd(II) IIPs, and NIPs Fig. . At lowe−1 are assigned to the stretching vibration frequency of C-N and -CONH- in amide, respectively. The peaks at 3550, 2950, 2560, 2350, 1740, and 1260 cm−1 are attributed to the stretching vibration frequency of −OH, C-H, S-H, C=O in esters and C-O, respectively. There is no shift among these vibrational absorption peaks in the three FTIR curves due to no coordination. As shown in curve b and curve c, the peak attributed to C-N shifted from 1390 to 1380 cm−1 after adding template ion Pd(II), indicating the coordination happened between the template ion Pd(II) and functional monomer. In addition, new absorption peaks appeared at 2080 and 1980 cm−1 in curve b may be caused by the elution process of Pd(II) which can lead to some changes in groups.Based on the absorption peaks and bands on FTIR spectra, many functional groups on the surface of absorbent material can be depicted and characterized for unleached Pd(II) IIPs, leached Pd(II) IIPs, and NIPs Fig. . It can The effect of the initial concentration of Pd(II) ions on the adsorption capacity of Pd(II) IIPs is shown in Fig. The effect of contact time on adsorption capacity and removal efficiency of Pd(II) IIPs for Pd(II) ions is shown in Fig. Figure The influence of multiple metals on the adsorption of Pd (II) by Pd(II) IIPs and NIPs is shown in Fig. To explore the adsorption capability of Pd(II) IIPs, two typical adsorption isotherm models, i.e., the Langmuir and Freundlich adsorption isotherms models Fig. , were utR^2 = 0.991) is much closer to 1 as compared with that from the Langmuire model (R^2 = 0.946), which suggests that Freundlich isotherm model is more suitable to describe the adsorption process of Pd(II) ions on Pd(II) IIPs. Freundlich model is an empirical equation, it is generally believed that the reciprocal of the Freundlich constant n is negatively correlated with the adsorption performance [n is between 0.1~0.5, it is easy to adsorb; when 1/n is greater than 2, it is difficult to adsorb. The 1/n value obtained from this experiment is about 0.39, which indicates that Pd(II) ions are easy to be adsorbed by Pd(II) IIPs.In the isotherm study, the correlation coefficient of the Freundlich isotherm model (formance . When 1/R2 = 0.971) than with the pseudo-first-order kinetic model (R2 = 0.896). With a theoretical equilibrium adsorption capacity of 5.085 mg/g which is closer to the experimental value of 5.042 mg/g, the adsorption of Pd(II) ions on Pd(II) IIPs is considered to be more in accordance with the pseudo-second-order kinetic model. The pseudo-second-order kinetic model assumes that the rate-controlling steps are mainly chemical adsorption processes between heavy metal ions and the adsorption sites on absorbents [In the kinetic study, the fitting result agrees better with the pseudo-second-order kinetic model  IIPs showed significant different imprinting effects. The UV spectra showed that 4-VP and ANA caused a large structural change after the template reacted with three functional monomers, while AAA basically did not change. According to the batch adsorption experiments, 4-VP performed as the most promising candidate functional monomer with a higher Pd(II) adsorption capacity than ANA and AAA. Formation of imprinted recognition sites, which was beneficial to Pd(II) IIPs adsorption for Pd(II) ions, was evidenced by the FTIR spectra. At optimal working conditions, a theoretical equilibrium adsorption capacity of 5.085 mg/g was obtained for Pd(II) ions by the synthesized Pd(II) IIPs. Compared with Cu(II), Zn(II), Ni(II), and Pt(II), Pd(II) IIPs showed high selectivity for Pd(II) ions. The isothermal results suggested that the Freundlich isotherm model demonstrated a better fitting for the adsorption process of Pd(II) on Pd(II) IIPs than the Langmuir isotherm model. Kinetic studies illuminated that the adsorption process could be best described by the pseudo-second-order kinetic model.


Progress in understanding liquid ethylene carbonate (EC) and propylene carbonate (PC) on the basis of molecular simulation, emphasizing simple models of interatomic forces, is reviewed. Results on the bulk liquids are examined from the perspective of anticipated applications to materials for electrical energy storage devices. Preliminary results on electrochemical double-layer capacitors based on carbon nanotube forests and on model solid-electrolyte interphase (SEI) layers of lithium ion batteries are considered as examples. The basic results discussed suggest that an empirically parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy. More sophisticated force fields might include molecular polarizability and Buckingham-model description of inter-atomic overlap repulsions as extensions to Lennard-Jones models of van der Waals interactions. Simple approaches should be similarly successful also for applications to organic molecular ions in EC/PC solutions, but the important case of Li An electrochemical voltage window is a primary concern for electrical energy storage applications of an electrolyte system, e.g., for lithium ion batteries (LIBs) and electrochemical double-layer capacitors (EDLCs). That voltage window is a primary issue for the energy density, but also a consideration in addressing safety. As a practical matter, that voltage window concern excludes aqueous electrolyte solutions . Non-aquUnderstanding that daunting range of chemical possibilities, including assessment of voltage windows, has put natural emphasis on screening enabled by electronic structure computations of theoretical chemistry –13. But Recent work has aimed at filling in the simulation basis for study of non-aqueous electrolyte solutions, i.e., for ethylene carbonate (EC) and propylene carbonate (PC) systems, at a molecular level Fig. . This reMolecular simulation is a useful tool for development of new materials. Development of effective, simplified molecular simulation models would enable enlightening simulation of dynamical phenomena of specific interest for electrical energy storage systems, i.e., transport through inhomogeneous or non-equilibrium materials, or of annealing processes involving those non-equilibrium materials.Electrochemical double-layer capacitors (EDLCs), or supercapacitors , presentAn even more prominent example of important molecular-scale kinetics involving inhomogeneous or non-equilibrium materials is that of Liry (LIB) . The SEIry (LIB) –23. Solury (LIB) , formingning gap , 26.Molecular calculations and simulations are typically a necessary prerequisite for basic molecular theories. Molecular calculations span a daunting range of algorithmic techniques, and a daunting range of space and time scales. For example, quantum calculations track electrons and can characterize decomposition of electrolytes at anode surfaces , 27, 28.Classical molecular dynamics simulation with model molecular force fields—‘force field molecular dynamics’ (FFMD)—inhabit a broader region of the simulation scale. Useful force field models can span a broad range of possibilities, from frankly ad hoc models, to models that are recognized as coarse-grained on a pragmatic basis, then including progressively more complicated models. Electron coordinates can be reintroduced into FFMD approaches by development of models that include molecular polarizabilities. Polarization of that type has been considered important for this problem . The pol}4 in PC .Highly specialized force fields and parameters are not readily available for common molecular simulation packages. Additionally, their complexity limits their use for study of transport behaviors for novel materials that interrogate molecularly long correlation times. This overview focuses on the pragmatic middle of FFMD simulations focused on non-polarizable force fields with empirical parameters.The FFMD simulations discussed specifically here were carried out using the GROMACS simulation package . Detailsp = 1 atm on the basis of the Parrinello-Rahman barostat [We identify secondary specific differences among those FFMD calculations discussed below, but we here provide several common features. These calculations adopted constant pressure simulation conditions with barostat . Temperabarostat , 40. A tbarostat .Extensions of such a simple force field model are interesting for the chemical physics of these problems. A Buckingham , 42 modee fields , 42. Thie fields –45. As we fields –5, the nWe will collect and discuss molecular simulation results on the EC and PC liquids and on solutions with electrolytes relevant to EDLC capacitors based on CNT forests , 46–48. ulations , 50, leaulations .In closing this introduction, we reemphasize the common goal of devising high-capacity, fast-charging, safe electrical energy storage systems . CommonlThe vapor pressures of EC and PC are low in regimes of practical use , 66, andparisons .Estimation of entclass1pt{minimaons Fig. , except ons Fig.  again diThe liquid density of standardly simulated PC at t denser  than thebout 50% . We expepulsions , 42.Fig.t, thus evaluating the self-diffusion coefficient, D. But we can take that characterization deeper per Fig.  before cfined by 4\documen liquids , 47, 68 nsidered , 47.D are only available for solutions of EC and PC with LiPFT over the range considered.Experimental results for ntration . Neverthntration  to thoseThe high dielectric constants of EC and PC liquids correlate naturally with the solubility of strong electrolytes, including lithium salts, in these solvents . Dielectt, M(t), of the liquid. The acf P(t) is then fit to the Fourier transform of a stretched exponential  model [Dielectric relaxation characterizes the ability of the material polarization to follow a changing applied electric field . Harmonifunction , 75–777\W) model ,8\documeThe agreement between computed and experimental relaxation times is encouraging: mphasize  the compA to be independent of T [The temperature dependence of the relaxation timesent of T , 79, 80,T<348 K) .Though the present computational results cover a broad temperature range, fitting beyond a single activation energy has not been warranted so far. Still, it would be interesting, and maybe of practical relevance, for subsequent experiments and modeling to investigate super-cooled conditions more thoroughly.The molecular electric fields at play on a molecular scale in ionic solutions are often much stronger than the laboratory electric fields used to measure dielectric constants. Thus, the equilibrium polarization responses to strong fields Fig.  are ofteBeyond clear potential for practical significance, EDLCs based on CNT forests offer the possibilities of better molecular-scale understanding of those solutions in contact with charged electrodes. This possibility is enabled by the simplicity of the electrode chemistry and the fact that the microstructures of CNT forests can be simple and controlled over interesting ranges . Thus EDOne consideration for simulating these systems is the modeling of the electrodes. The simple model exemplified in Fig. LC cases . The comThe physical conclusion is that the EDLC/CNT calculations discussed above with molecular ions Fig.  conservaWe emphasize that realistic molecular models of EDLC/CNTs are feasible for direct numerical simulation of the pore filling and the electrical characteristics , 91, 92.The results discussed in previous sections suggest that a parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy , 46–48. We have compared results using partial charges available in the standard OPLS-AA distribution for EC and PC solvents  to resulQCT is based on the study of the occupancy of an inner shell of an Licument}+ . We use cument}+ , 10611\dFor analyzing the MD results, we use the direct QCT approach 13\documed to Eq.  with theThe free energies of Lions Fig.  compare y Marcus . No expePositive transfer free energies favor lithium ion solvation by water compared with either carbonate solvent. From the perspective of the cluster QCT calculations, the replacement free energy, reflecting the availability of the solvent molecules as ligands, is the foremost factor leading to that result. Comparing EC and PC transfer free energies, again from the perspective of cluster QCT, the solvation of the bare EC/PC molecules serving as ligands is decisive in arriving at a positive free energy of transfer from PC to EC, with EC being slightly smaller.Radial distributions (rdfs) of carbonyl O of EC and PC with Limentclasspt{minimain water  and PC ain water  and neutin water , 125 resulations . The coofraction . Interesfraction , 127. ThD, according toThe Li results  were obt results . The resThe computed transference numbers of 0.35 (EC) and 0.31 (PC) are consistent with previous NMR  and impeIn summary, changes to the partial charges on PC and EC solvents alter solvation structure and transport properties of Limentclasspt{minimaons Fig. , and traons Fig. , we idenThe discussion above encourages us to apply such an empirical non-polarizable force field to study non-aqueous electrolytes more broadly. Thus we extended our effort to simulate Lite (EDC) . The Li\nts Fig.  shows thanalysis  confirmeThe basic results discussed suggest that an empirically parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy. More sophisticated force fields might include molecular polarizability and Buckingham-model description of inter-atomic overlap repulsions as extensions of Lennard-Jones models of van der Waals interactions. Simple approaches should be similarly successful also for applications to organic molecular ions in EC/PC solutions, but the important case of Li


Transgenic Caenorhabditis elegans (UA57) overproducing dopamine was exposed to caffeine for 7 days and monitored by observing GFP-tagged dopaminergic (DA) neurons via fluorescence microscopy. Caffeine (10 mM) prevented neuronal cell loss in 96% of DA neurons, with a mean GFP intensity that is 40% higher than control (0.1% DMSO). To confirm if cAMP plays a role in the observed neuroprotection by caffeine, cAMP levels were elevated via forskolin (10 μM), an adenylyl cyclase activator. Forskolin (10 μM) exposure did not confer neuroprotection and was similar to control (0.1% DMSO) at the 7th day, suggesting that cAMP is not the sole secondary messenger utilized. Rotigotine (160 μM), a dopamine D2-like receptor (DOP2R) agonist, was not able to confer significant neuroprotection to the nematodes. This suggests that DOP2R activation is necessary but insufficient to mimic neuroprotection by caffeine. Lastly, co-administration of caffeine (10 mM) with olanzapine (160 μM), a DOP2R antagonist, eliminated neuroprotection. This suggests that the protective effect must involve both adenosine receptor antagonism and activation of DOP2Rs. Taken together, we show that caffeine protects DA neurons from dopamine-induced neurodegeneration and acts by modulating adenosine receptor-DOP2R interactions in C. elegans.Previous studies have suggested that caffeine reduces the risk of L-DOPA-induced dyskinesia. However, caffeine is also known to promote dopamine signaling, which seemingly contradicts this observed effect. To this end, the study aimed to clarify the mechanism of caffeine neuroprotection  Drosophila melanogaster , a neurodegenerative, arguably inflammatory disease  ortholog. We show that either DOP2R agonism or AR antagonism is necessary but insufficient in conferring neuroprotection, supporting previous findings. Lastly, we attempt to solve the paradox of dopamine signaling by proposing DOP2R availability as an alternative, coherent explanation for increased dopamine signaling in C. elegans.In this study, we show that caffeine protects DA neurons from neurodegeneration induced by excessive biosynthesis of endogenous L-DOPA. Further, we show that caffeine acts by synergizing dopamine D2-like receptor (DOP2R) activation with antagonism of a putative adenosine receptor , after which 125 μL each of 1 M CaCl2, 5 mg/mL cholesterol in 70% EtOH and 1M MgSO4 were added, followed by 3.125 mL of 1M KPO4. The solution was mixed vigorously, and was then poured into petri plates  using sterile techniques. After the NGM hardened, 100 μL of E. coli strain OP50 in aqueous solution was added. For each treatment group, 20 C. elegans strain UA57 nematodes at stage L4 to young adulthood were worm-picked onto each plate. C. elegans is a free-living, non-parasitic nematode, while the E. coli strain OP50 is non-pathogenic; thus, all procedures were done in accordance with the precautions for Biosafety Level 1.For this study, nematodes in OP50-seeded nematode growth media (NGM) plates were prepared according to the protocol of Steirnagle , with sl2ARs at 10 μM concentration —implying its full inhibitory effect at the said concentration , forskolin (10 μM), caffeine (10 mM), rotigotine (160 μM), and olanzapine+caffeine (160 μM). For olanzapine+caffeine, 320 μM of olanzapine was mixed with 20 mM caffeine in a volume ratio of 1:1, to obtain final olanzapine and caffeine concentrations of 160 μM and 10 mM, respectively. The concentration of caffeine was chosen based on a previous study comparing caffeine concentrations from 5 to 100 mM, showing optimal worm lifespan extension delay of age-associated paralysis at 10 mM caffeine , after which the solution was incubated at ~25°C for 1 h on a rotator. After settling and three rinses of 1M KPO4, the volume was reduced to 100 μL followed by 300 μL of 1M KPO4 and 600 μL of 2-propanol. The solution was allowed to stand for 15 min and ~0.9–1.0 μL of supernatant was taken from the solution depending on the remaining supernatant—taking care to leave ~100 μL of supernatant in which the nematodes are understood to be immersed in. Sudan black  was then added and the suspension was incubated at room temperature overnight on a rotator. The following day, black supernatant was drained via micropipetting, after allowing the suspension to settle. The precipitates were transferred to a clear NGM plate, and nematodes were viewed for fix-stained lipid stores via bright-field microscopy (10x).To monitor changes in lipid stores, fixed Sudan Black staining was performed on s et al. , with slpost-hoc Bonferroni-Holm method was employed to correct for errors due to multiple comparisons. For all statistical analyses, “*” denotes significance at p < 0.05. For all graphs, the mean of each data set was plotted with its respective standard error of measurement (mean ± SEM).The effect of each treatment group per day were analyzed and generally compared with one another for variations via the one-way analysis of variance (ANOVA). To determine the difference between each treatment group, a C. elegans nematodes were exposed to forskolin (10 μM) and caffeine (10 mM), caffeine preserved DA neurons consistently for a span of 7 days , with caffeine having an average GFP intensity comparable with previous days. Overall, caffeine-exposed C. elegans DA neurons were noted to have been protected and showed a brighter average GFP intensity at the end of 7 days as compared with forskolin- and DMSO-exposed nematodes  interaction. While significant differences in the maximum and minimum GFP intensities per neuron exposed to caffeine and forskolin were observed at days 5 and 7, the results imply that both forskolin and caffeine significantly increase GFP intensity compared with vehicle, but the difference between forskolin and caffeine may not readily be observed in vivo. These imply, at least, that the brighter average GFP intensity  and olanzapine (160 μM) to agonize and antagonize dopamine D2-like receptors (DOP2Rs), respectively. Interestingly, rotigotine treatment led to a prognosis similar to caffeine . Even if significance was found between nematodes exposed to rotigotine and olanzapine + caffeine, it is unlikely to be biologically relevant as evidenced by the comparable percentages and error bars. In addition, since rotigotine is an agonist of DOP2Rs, these results suggest that DOP2R agonism is not sufficient to mimic the level of protection conferred by caffeine. Therefore, DOP2R activation is necessary but insufficient in mimicking caffeine-induced neuroprotection. On the other hand, olanzapine antagonizes DOP2Rs. When caffeine was administered with olanzapine, the protection seen previously was lost. Since the combination leads to antagonism of both putative adenosine and dopamine D2-like receptors, results suggest that neither DOP2R activation alone nor adenosine receptor antagonism alone is sufficient to mimic caffeine-induced neuroprotection, and it is likely that adenosine receptors interact with DOP2Rs when antagonized. These results support an interaction seen in higher vertebrate models, where adenosine receptors normally antagonize DOP2Rs. Therefore, administration of caffeine may increase DOP2R availability, which is an effect countered by olanzapine . In this way, they proposed that caffeine may in fact worsen dopamine-related neurotoxicity and motor dysfunction , and that it is the antagonism of A2A ARs that lead to dopamine receptor sensitization and therefore aggravation of dopamine-related symptoms  could increase availability of DOP2Rs to dopamine and enhance the dopamine response, which would then modulate neuroprotection. The key concept in this mechanism is the autoreceptor function of DOP2Rs. These receptors, primarily found in DA neurons as presynaptic receptors, control both the rate and amount of dopamine release by DA neurons—the absence of which could lead to Parkinson's disease and schizophrenia  antagonizing AR orthologs thereby sensitizing DOP2Rs and enhancing their inhibitory action on dopamine release, and (2) modulating downstream cascades leading to neuroprotection. Hence, DOP2R action is due in part to its nature as an autoreceptor - and caffeine-treated nematodes, which were markedly similar to each other. This suggests that the cAMP potentiation of forskolin and caffeine was essentially the same in the concentrations used. Since forskolin was not able to confer neuroprotection, we propose that cAMP is not the sole second messenger being utilized by caffeine. Administration of rotigotine (160 μM) did not confer neuroprotection to C. elegans—indicating that mere agonism of DOP2Rs is not sufficient. Co-administration of olanzapine with caffeine eliminated neuroprotection—suggesting that both DOP2Rs and ARs are necessary to confer neuroprotection, but neither are sufficient on their own. We therefore show for the first time that caffeine does not increase dopamine synthesis but increases the availability of DOP2Rs in C. elegans, and that its binding to putative AR orthologs communicates with DOP2Rs to regulate dopamine overproduction and confer neuroprotection against induced neurodegeneration, through second messengers other than cAMP.In this study, we show that caffeine (10 mM) protects 96% of DA neurons against dopamine-induced neurodegeneration in transgenic All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The cyclization occurred under mild conditions and without the need to suspend the crystals in solvent. The ability of CMFs to host purely gas‐induced reactions is further highlighted by the subsequent sequential oxidation reaction of cyclized 7‐iodo‐12‐phenylindenophenalene (ipp) with molecular oxygen derived from air, yielding 12‐hydroxy‐7‐iodo‐2‐phenylindenophenalen‐1(12H)‐one (hipp).A vapor‐induced cyclization has been observed in the host environment of a crystalline molecular flask (CMF), within which 1,8‐bis(2‐phenylethynyl)naphthalene (bpen), a diarenynyl system primed for cyclization, was exposed to iodine vapor to yield the corresponding indenophenalene species. The cyclization process, unique in its vapor‐induced, solvent‐free nature, was followed spectroscopically, and found to occur concurrently with the displacement of lattice solvent for molecular iodine in CMF⋅0.75 bpen⋅2.25 CHCl The advent of crystalline molecular flasks2)3(tpt)2]⋅x(G), where G=guest.A range of chemical reactions have been observed within CMFs, including the conversion of amines into imines,2)3(tpt)2]⋅0.75 bpen⋅2.25 CHCl3⋅H2O (1). The chloroform hydrogen atom attached to C(65) is well aligned to participate in a weak C−H⋅⋅⋅π hydrogen bond to an alkyne group of bpen equidistant between C(56) and C(57), with an observed distance of approximately 3.45 Å. This interaction, coupled with a pair of π–π stacking interactions between the adjacent tpt ligand and the naphthalene ring (3.8 Å ring intercentroid distance) and alkyne group  of bpen, serves to order the guests within the pores of 1. The location of bpen guests within the CMF framework 1 is shown in Figure Prior to loading bpen into the CMF, the solvated framework containing cyclohexane was first prepared by a solvent‐ exchange route from a precursor framework that had been synthesized from methanol and nitrobenzene, as reported by Fujita and co‐workers.b axis and the [101] direction.2 nodes, which provide a polarizing environment. These factors are expected to promote the facile adsorption of molecular iodine from the gas phase. To test this postulate, crystals of 1 were removed from their mother liquor, briefly dried in air, and placed in a small glass vial. This small vial was transferred into a larger vial containing solid iodine crystals and sealed, creating an atmosphere of iodine vapor in air that is capable of infusing into the crystals. Over several days the crystals changed color from yellow to black, coinciding with the uptake of molecular iodine. Single‐crystal X‐ray diffraction was performed on the black crystals after seven days, resulting in the identification of a structure containing molecular iodine and a region of highly disordered electron density, which was identified as the likely location of the guest cyclization product ipp: its presence was subsequently confirmed by NMR spectroscopy (see below). As expected, the structure of the host framework is comparable with that of 1. It is reasonable to posit that the increase in disorder of the cyclized ipp guest in 2 relative to that of bpen in 1 may be due to the displacement of ordering solvent molecules by electronically diffuse molecular iodine. While the substantial disorder prevented the unambiguous identification of a single location for the ipp molecule, a structural model is presented in the Supporting Information in which the partially occupied, heavily restrained ipp molecule is included to illustrate its likely location within the pore of the ordered framework. The asymmetric unit, which includes the heavily restrained ipp molecule modelled within the region of highly disordered electron density, is shown in Figure 2, molecular iodine is included within the pores, again disordered over several identifiable and discrete positions. In each case, the total occupancy of I2 is between 1.75 and 2.1 molecules per [(ZnI2)3(tpt)2] unit, although the highly disordered nature of this material means that these values should be interpreted with caution. Although the overall quality of this structure was relatively low, further experiments were performed to unambiguously confirm the composition of 2, which was determined to be [(ZnI2)3(tpt)2]⋅0.75 ipp⋅0.25 CHCl3⋅2 I2. This result was based on a combination of analytical techniques to determine the nature of the guest species (see below).In the absence of bpen guests and solvent, the CMF possesses large 2D channels that propagate down the crystallographic 2 were digested in [D7]DMF, and the resulting mixture was analyzed by 1H NMR spectroscopy . The spectrum contained no evidence of bpen; however, two new cyclized species were identified in a ratio of 1:1.6. The sample was subjected to column chromatography using hexane as the eluent to separate the two components. The major component eluted first and was determined to be the expected cyclization product ipp by 1H NMR spectroscopy (see below) as well as by X‐ray diffraction of the recrystallized product . The minor component was only isolable in trace amounts, but high‐resolution mass spectrometry  determined the unknown molecular ion to have a m/z ratio of 509.0005. This species was matched to an oxidized product of ipp . The conversion of ipp into hipp in the presence of molecular oxygen has been observed previously,Single crystals of 1H NMR spectroscopy at intervals of 12 hours, 3 days, and 7 days  had occurred after 12 hours despite the dramatic change in crystal color from yellow to black, suggesting that either iodine infuses into the crystal prior to mediating the cyclization, or that only the surface of the crystals has undergone reaction at this time. After three days, however, 85 % of the loaded bpen had cyclized to ipp, as determined by comparing the ratio of the residual meta‐phenyl resonances of bpen at 7.26 ppm to the new aromatic resonances of ipp at 7.05 ppm and 9.17 ppm. After seven days, bpen was no longer observable spectroscopically, and apart from residual tpt derived from digestion of the CMF and a signal at 8.39 ppm, which was assigned to chloroform, ipp was the dominant species observed. Interestingly, despite rigorous exclusion of oxygen from the point of iodine introduction, trace amounts of hipp were still observed in the spectra recorded after three and seven days. These findings can be attributed to the uptake of small amounts of molecular oxygen by 1 during the air‐drying step prior to transfer into the glove box. No evidence of hipp was observed after 12 hours, demonstrating the necessity of the iodine‐mediated cyclization step prior to hipp formation and supporting the conclusion that ipp is initially formed in the iodine‐gas‐mediation cyclization with subsequent transformation to hipp within the molecular flask in the presence of O2.To better quantify the initial cyclization of bpen to ipp, the iodine infusion experiment was repeated in the inert argon atmosphere of a glove box. Single crystals held in this environment were analyzed by s Figure . DigestiThe cyclization of bpen to ipp requires a single iodine atom from molecular iodine and liberates a proton. The remaining iodide likely forms gaseous hydrogen iodide, which is liberated from the CMF under inert conditions. Under aerobic conditions, the hydrogen iodide may react further with molecular oxygen to give molecular iodine and water.1 and 2, thermogravimetric analysis was employed . Independent analysis of bpen prior to loading into the CMF showed that the guest is thermally stable up to 230 °C, after which time it loses approximately 50 % of its mass up to 400 °C. CMF 1 loses 8.1 % by mass in two steps up to a temperature of 200 °C, which is consistent with the crystallographic assignment of two chloroform molecules and one water molecule (predicted: 11.8 %). The iodine‐infused CMF 2 was found to have lost 19.9 % of its mass by 230 °C, which is consistent with the surmised presence of two equivalents of molecular iodine within the CMF (predicted: 20.0 %). The elemental analysis results for framework 1 were indicative of incomplete bpen loading, likely involving substitutional disorder of chloroform, with a ratio of 75 % bpen to 25 % CHCl3, providing matching C, H, and N percentages . This composition was used to fix the occupancy of the bpen molecule in 1 in the crystal structure, but it should be noted that it is possible to obtain variation between individual crystals with regard to guest loading, which is a known phenomenon in CMF systems.2 was also consistent with a loading ratio of 0.75, with the remaining 0.25 assigned to residual chloroform based on 1H NMR spectroscopic and microanalytical evidence .To better evaluate the degree of solvation within the CMFs 1H NMR spectroscopy. Running the transformation in air resulted in a process of sequential gas‐mediated reactions, first iodine‐mediated conversion of bpen into ipp, followed by oxidation of ipp to hipp. The latter oxidation step proceeded with a conversion of more than 35 % after seven days without optimization, greatly improving on past solution‐based reports.In conclusion, we have described gas‐mediated reactions that occur quantitatively within a CMF under mild conditions and without the need to activate the framework beyond the initial loading of reagents. Furthermore, the reaction occurred without any need to suspend the CMF in a solvent, simplifying methods for reaction monitoring. In the absence of air, bpen was converted into the cyclization product ipp by molecular iodine after seven days, as monitored by As a service to our authors and readers, this journal provides supporting information supplied by the authors. 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