Surface activated zinc-glutarate for the copolymerization of CO2 and epoxides.

Zinc-glutarate (ZnGA) is a promising catalyst that can form polymers from CO2 and epoxides, thereby contributing to the development of CO2 utilization technologies and future sustainability. One of the obstacles to commercializing ZnGA in polymer industries is its low catalytic activity. In this study, we introduced activated two-dimensional (2D) ZnGA to improve its catalytic activity in polymerization. The morphology-controlled 2D ZnGA was treated with H3Co(CN)6, and a porous granular-type Co-modified ZnGA (Co-ZnGA) was prepared. The morphology of 2D ZnGA is a prerequisite for the activation by H3Co(CN)6. The catalytic properties of Co-ZnGA were evaluated by copolymerization of various epoxides and CO2, and exhibited catalytic activity of 855, 1540, 1190, and 148 g g-cat-1 with propylene oxide, 1,2-epoxyhexane, 1,2-epoxybutane, and styrene oxide, respectively. This study provided a new strategy using 2D ZnGA instead of conventional ZnGA for increasing the catalytic activity in CO2 polymerization.

Altered subcallosal and posterior cingulate cortex-based functional connectivity during smoking cue and mental simulation processing in smokers.

BACKGROUND: Long-term cigarette smoking induces sensitization of incentive salience and conditioning of contextual cues which involves brain function alteration across multiple regions. Understanding how nicotine affects hub-based functional connectivities involved in affective and cognitive function can help us determine the treatment strategy for nicotine dependence. METHOD: Functional MRI was conducted on 30 smokers and 30 non-smokers while mentally simulating neutral and smoking hand movements. Smoking cue and mental simulation processing-related changes in functional connectivity strengths of the subcallosal and posterior cingulate cortex (SCC and PCC) with major brain network nodes were examined. RESULTS: Compared to non-smokers, smokers showed cue-induced SCC functional connectivities which were enhanced with the intraparietal sulcus and reduced with the medial prefrontal cortex. The PCC activation and functional connectivity enhancements with the anterior insula cortex and rostro-lateral prefrontal cortex was found during smoking mental simulation. The PCC-lateral prefrontal cortex functional connectivity correlated with nicotine dependence severity. CONCLUSION: The present results demonstrate that smokers can be identified by cue-induced SCC functional connectivity strength decline and increment in the default mode and dorsal attention network nodes. However, nicotine dependence was associated with smoking mental simulation-related PCC-lateral prefrontal cortex functional connectivity strength, suggesting that the development of nicotine dependence may depend on the strength of coupling between the default mode network and the central executive network at the cognitive level.

Curcumin Treatment in Combination with Glucose Restriction Inhibits Intracellular Alkalinization and Tumor Growth in Hepatoma Cells.

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein-protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GßL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.

Factors associated with physical activity of breast cancer patients participating in exercise intervention.

PURPOSE: Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. METHODS: Three hundred fifty-six participants were assigned to two groups: "Smart After-Care" (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire-Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. RESULTS: At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received "Smart After-Care" have a 64% higher chance of increasing physical activity. CONCLUSION: Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. "Smart After-Care" was more effective than education only in increasing physical activity.

Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc.

Effects of exercise intervention in breast cancer patients: is mobile health (mHealth) with pedometer more effective than conventional program using brochure?

PURPOSE: To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL). METHODS: The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group. RESULTS: Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group. CONCLUSIONS: Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.

Regulation of HK2 expression through alterations in CpG methylation of the HK2 promoter during progression of hepatocellular carcinoma.

Hexokinase 2 (HK2) is a rate-determining enzyme in aerobic glycolysis, a process upregulated in tumor cells. HK2 expression is controlled by various transcription factors and epigenetic alterations and is heterogeneous in hepatocellular carcinomas (HCCs), though the cause of this heterogeneity is not known. DNA methylation in the HK2 promoter CpG island (HK2-CGI) and its surrounding regions (shore and shelf) has not previously been evaluated, but may provide clues about the regulation of HK2 expression. Here, we compared HK2 promoter methylation in HCCs and adjacent non-cancerous liver tissues using a HumanMethylation450 BeadChip array. We found that, while the HK2-CGI N-shore was hypomethylated, thereby enhancing HK2 expression, the HK2-CGI was itself hypermethylated in some HCCs. This hypermethylation suppressed HK2 expression by inhibiting interactions between HIF-1α and a hypoxia response element (HRE) located at -234/-230. HCCs that were HK2negative and had distinct promoter CGI methylation were denoted as having a HK2-CGI methylation phenotype (HK2-CIMP), which was associated with poor clinical outcome. These findings indicate that HK2-CGI N-shore hypomethylation and HK2-CGI hypermethylation affect HK2 expression by influencing the interaction between HIF 1α and HRE. HK2-CGI hypermethylation induces HK2-CIMP and could represent a prognostic biomarker for HCC.

The diagnostic ability of 18F-FDG PET/CT for mediastinal lymph node staging using 18F-FDG uptake and volumetric CT histogram analysis in non-small cell lung cancer.

OBJECTIVES: To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC). METHODS: One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology. RESULTS: Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %. CONCLUSIONS: LN density is useful for the characterization of LNs with mild 18F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both 18F-FDG uptake and LN density. KEY POINTS: • SUVmax showed the highest diagnostic ability for detecting malignant LNs. • LN density was useful in characterization of LNs with mild FDG uptake. • SUVmax and LN density together could stratify the risk of LN metastasis.

Prognostic Significance of ¹8F-FDG Uptake in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization or Concurrent Chemoradiotherapy: A Multicenter Retrospective Cohort Study.

UNLABELLED: This study aimed to assess the prognostic value of (18)F-FDG uptake in hepatocellular carcinoma (HCC) patients who had transarterial chemoembolization (TACE) or concurrent intraarterial chemotherapy with external-beam radiotherapy (CCRT) and to compare the prognosis between patients treated with TACE and those with CCRT according to (18)F-FDG uptake. METHODS: Two hundred fourteen intermediate-to-advanced-stage HCC patients without extrahepatic metastasis who underwent staging (18)F-FDG PET/CT before TACE (153 patients) or CCRT (61 patients) were recruited from 7 hospitals. Progression-free survival (PFS) and overall survival (OS) were compared using an optimal cutoff value for tumor-to-normal liver uptake ratio (TLR). Further, PFS and OS were compared according to treatment modalities (TACE vs. CCRT) using the same TLR cutoff value. RESULTS: On multivariate analysis, age and TLR were independent prognostic factors for PFS (P< 0.050). For OS, Child-Pugh classification and TLR were independent prognostic factors (P< 0.050). When the TLR was greater than 2.0, patients treated with CCRT showed significantly better PFS and OS than those treated with TACE after adjusting for tumor size and number (P= 0.014, for all). In contrast, there was no significant difference in PFS and OS between patients treated with TACE or CCRT when the TLR was 2.0 or less. CONCLUSION: (18)F-FDG uptake was an independent prognostic factor for PFS and OS in HCC patients treated with TACE or CCRT. Especially, in HCCs with high (18)F-FDG uptake, patients treated with CCRT showed better survival than those treated with TACE. (18)F-FDG PET/CT may help determine the treatment modality for intermediate-to-advanced-stage HCCs.

Transgenic mouse models generated by hydrodynamic transfection for genetic studies of liver cancer and preclinical testing of anti-cancer therapy.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.