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As the demand for high-density, high-performance technologies in semiconductor systems increases, efforts are being made to mitigate and optimize the issues of high current density and heat generation within interconnects to ensure reliability. While interconnects are the most fundamental pathways for transmitting current signals, there has been relatively little research conducted on them compared to individual unit devices from the perspective of overall system performance. However, as integration density increases, the amount of loss in interconnects also rises, necessitating research and development to minimize these losses. In this study, we propose a method to analyze power efficiency by utilizing the differences between simulation results and measured results of interconnect structures. We confirmed that the difference between theoretical resistance values and actual measured values varies with the contact area ratio between metal lines and vias, and we analyzed the power efficiency based on these differences. Using the findings, we proposed and validated a structure that can improve power efficiency. This study presents a method to analyze power efficiency and suggests ways to achieve higher power efficiency within the limited specifications of interconnects. This contributes to enhancing power efficiency and ensuring reliability, thereby preserving the performance of the overall system in highly integrated semiconductor systems.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: To determine the impact of implementing 2 technologies in succession, the Carousel system and XR2 robot, in a hospital central pharmacy. The study examined the technologies' impact on workload shifted from fully human-involved, labor-intensive filling from shelves to Carousel and/or XR2, prevention of dispensing errors, and efficiency., Methods: Implementation occurred in 3 phases from August 2021 through October 2022. In phase I, medications were manually filled from the shelves for immediate doses and automated dispensing cabinet stock. RobotRx was used for unit-dose (UD) carts. In phase II, the Carousel system was introduced, while RobotRx was used for UD carts. In phase III, the XR2 robot was added and RobotRx was decommissioned. Epic data and time studies were utilized and analyzed with ANOVA., Results: Over the 3 phases of implementation, workload shifted away from filling from the shelves, with 2,479, 1,044, and 864 orders filled from the shelves for phase I through phase III, respectively. The Carousel workload was 1,234 orders (phase II) and 348 orders (phase III). Nearly 71% of the workload was shifted to the XR2. The overall prevented error rate did not significantly change from phase I to phase II, remaining at 0.5%. In comparison, the error rate significantly decreased to 0.41% in phase III. Use of the Carousel system resulted in a significant reduction in dispensing errors compared to manual filling from the shelves. Use of the XR2 robot resulted in a dispensing error rate of 0%. The savings in time when using both Carousel and XR2 led to a decrease in full-time equivalents of 0.77 for pharmacists and 1.76 for pharmacy technicians., Conclusion: Carousel and/or XR2 significantly shift workload from manual filling to automated technologies, decrease dispensing errors, and improve efficiency, reducing pharmacist and technician workload. Time saved could allow staff to spend more time on patient-centric tasks., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Hispidin, a polyphenol component mainly derived from the medicinal mushroom species Phellinus and Inonotus , shows promise for biomedical applications, yet its potential in wound healing remains largely unexplored. This research investigates the wound healing effects of hispidin through in vitro and in vivo experiments, while also evaluating its antimicrobial properties and safety profile., Methods: In vitro scratch assays were conducted to evaluate the impact of hispidin on the migration of NIH-3T3 cells. The wound healing potential of hispidin was assessed in rats using excision wounds, dead space wounds, and linear incisions, treated with various topical ointments including a simple ointment, 2.5% ( w / w ) and a 5% ( w / w ) hispidin ointment, and a 0.2% ( w / w ) nitrofurazone ointment, administered at 0.2 g daily for 14 days., Results: Hispidin demonstrated antimicrobial properties and was particularly effective against Staphylococcus epidermidis . Hispidin enhanced NIH-3T3 cell viability, and promoted wound closure in scratch assays, correlating with increased levels of FGF21, TGF-β1, EGF, and VEGF. In excision wound models, the 5% ( w / w ) hispidin ointment improved wound contraction, epithelialization, tissue regeneration, fibroblast activity, and angiogenesis. In the granulation tissue from dead space wound models, hispidin reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and lipid peroxidation, while increasing anti-inflammatory cytokines (IL-10) and antioxidant activities (SOD, GPx, CAT), along with connective tissue markers like hydroxyproline, hexosamine, and hexuronic acid. Hispidin also enhanced wound breaking strength in incision models. Acute dermal toxicity studies indicated no adverse effects at 2000 mg/kg., Conclusions: These findings highlight hispidin's potential in wound care, demonstrating its antimicrobial, regenerative, and safety properties.

Introduction: Percussionists stand out for their expertise in rhythm, with the network for musical rhythm (NMR) serving a vital neurological function in their improvisation, which is deeply rooted in comprehensive musical knowledge. Our research examines the central representations of various improvisation tactics used by percussionists and investigates the interactions between the NMR and other relevant neural networks., Methods: Twenty-five percussionists participated in functional magnetic resonance imaging (fMRI) sessions, which included two cognitive strategies of improvisation. Structural improvisation (SIMP) emphasized rhythmic patterns, while free improvisation (FIMP) focused on musical spontaneity. Sight-reading scenario served as the reference condition. Paired t -tests were utilized for comparative analyses., Results: The findings revealed a dynamic interplay characterized by increased activity in the executive control network and NMR, along with decreased activity in the default mode network during SIMP. During FIMP, heightened activity was observed in the executive control network, NMR, limbic, and memory systems. In both SIMP vs. sight-reading and FIMP vs. sight-reading comparisons, the visual network's activity decreased, a trend also observed in the comparative analysis of FIMP vs. SIMP., Discussion: In SIMP, percussionists leverage external rhythmic signals, resulting in heightened NMR and ECN activity and reduced DMN activity. In contrast, FIMP is characterized by a rise in activity within the NMR, ECN, limbic system, memory system, and reward system, underscoring the vital roles of motivation and memory in the rapid production of spontaneous musical ideas within set frameworks. The diminished activity in the visual network during FIMP compared to SIMP suggests less reliance on visual stimuli in FIMP. These findings suggest that various improvisational tactics may engage different neural pathways., Competing Interests: 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., (Copyright © 2024 Liao, Yang, Yu, Huang, Hong, Li, Chen and Hsieh.)

The excessive activation of glutamate in the brain is a factor in the development of vascular dementia. γ-Oryzanol is a natural compound that has been shown to enhance brain function, but more research is needed to determine its potential as a treatment for vascular dementia. This study investigated if γ-oryzanol can delay or improve glutamate neurotoxicity in an in vitro model of differentiated HT-22 cells and explored its neuroprotective mechanisms. The differentiated HT-22 cells were treated with 0.1 mmol/L glutamate for 24 h then given γ-oryzanol at appropriate concentrations or memantine (10 µmol/L) for another 24 h. Glutamate produced reactive oxygen species and depleted glutathione in the cells, which reduced their viability. Mitochondrial dysfunction was also observed, including the inhibition of mitochondrial respiratory chain complex I activity, the collapse of mitochondrial transmembrane potential, and the reduction of intracellular ATP levels in the HT-22 cells. Calcium influx triggered by glutamate subsequently activated type II calcium/calmodulin-dependent protein kinase (CaMKII) in the HT-22 cells. The activation of CaMKII-ASK1-JNK MAP kinase cascade, decreased Bcl-2/Bax ratio, and increased Apaf-1-dependent caspase-9 activation were also observed due to glutamate induction, which were associated with increased DNA fragmentation. These events were attenuated when the cells were treated with γ-oryzanol (0.4 mmol/L) or the N-methyl-D-aspartate receptor antagonist memantine. The results suggest that γ-oryzanol has potent neuroprotective properties against glutamate excitotoxicity in differentiated HT-22 cells. Therefore, γ-oryzanol could be a promising candidate for the development of therapies for glutamate excitotoxicity-associated neurodegenerative diseases, including vascular dementia.

Introduction: Dance education fosters embodied metacognition, enhancing student's creativity. This study examines the crucial role of functional connectivity (FC) between the neural correlates of metacognition (NCM) and dance (NCD) as the neurological foundation for dancers' embodied metacognition. The investigation also explores whether these consolidated FCs inform the general creativity in dancers., Methods: The research involved 29 dancers and 28 non-dancer controls. The study examined resting-state connections of the NCM through seed-based FC analysis. Correlation analyses were employed to investigate the connections between the targeted NCM-NCD FCs, initiated from the a priori NCM seed, and general creativity., Results: Dancers demonstrated heightened FC between NCM and NCD compared to non-dancer controls. The targeted regions included the putamen, globus pallidus, posterior cerebellum, and anterior insula of NCD. The dancers exhibited higher originality scores. In dancers, the enhanced FC showed a negative correlation with originality and a positive correlation with flexibility. Conversely, the controls exhibited no significant correlations., Discussion: Extended dance training enhances the NCM-NCD connection signifying embodied metacognition. This interconnectedness may serve as the neural predisposition for fostering general creativity performance in dancers. Dancers with heightened levels of originality could leverage the relatively weaker NCM-NCD FCs to facilitate better integration and coordination of creative cognitive processes. Our findings suggest that the consolidated functional connections as sculpted by domain-specific training may inform general creativity., Competing Interests: 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., (Copyright © 2024 Yang, Yu, Hong, Cheng, Li, Yeh, Chen and Hsieh.)

Introduction: The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP)., Methods: The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions., Results: Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule., Discussion: PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education., Competing Interests: 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., (Copyright © 2024 Liao, Yang, Yu, Huang, Hong, Li, Chen and Hsieh.)

Competing Interests: The authors declare that they have no conflict of interest.

Introduction: This study aimed to examine the white matter characteristics of visual artists (VAs) in terms of visual creativity and the structural connectivity within the cortical visual system., Methods: Diffusion spectrum imaging was utilized to examine the changes in white matter within the cortical visual system of a group of VAs ( n  = 25) in comparison to a group of healthy controls matched for age and education ( n  = 24). To assess the integrity of white matter and its relationship with visual creativity, we conducted a comprehensive analysis using region-based and track-specific tractographic examinations., Results: Our study uncovered that VAs demonstrated increased normalized quantitative anisotropy in specific brain regions, including the right inferior temporal gyrus and right lateral occipital gyrus, along with the corresponding white matter fiber tracts connecting these regions. These enhancements within the cortical visual system were also found to be correlated with measures of visual creativity obtained through psychological assessments., Discussion: The noted enhancement in the white matter within the cortical visual system of VAs, along with its association with visual creativity, is consistent with earlier research demonstrating heightened functional connectivity in the same system among VAs. Our study's findings suggest a link between the visual creativity of VAs and structural alterations within the brain's visual system., Competing Interests: 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., (Copyright © 2023 Hong, Yang, Cheng, Li, Tseng, Yeh, Yu, Chen and Hsieh.)

Background: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance., Methodology: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle., Results: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule., Conclusions: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

Introduction: Dance is an art form that integrates the body and mind through movement. Dancers develop exceptional physical and mental abilities that involve various neurocognitive processes linked to embodied cognition. We propose that dancers' primary trait representation is movement-actuated and relies on the extended mirror neuron system (eMNS)., Methods: A total of 29 dancers and 28 non-dancer controls were recruited. A hierarchical approach of intra-regional and inter-regional functional connectivity (FC) analysis was adopted to probe trait-like neurodynamics within and between regions in the eMNS during rest. Correlation analyses were employed to examine the associations between dance training, creativity, and the FC within and between different brain regions., Results: Within the eMNS, dancers exhibited increased intra-regional FC in various brain regions compared to non-dancers. These regions include the left inferior frontal gyrus, left ventral premotor cortex, left anterior insula, left posterior cerebellum (crus II), and bilateral basal ganglia (putamen and globus pallidus). Dancers also exhibited greater intrinsic inter-regional FC between the cerebellum and the core/limbic mirror areas within the eMNS. In dancers, there was a negative correlation observed between practice intensity and the intrinsic FC within the eMNS involving the cerebellum and basal ganglia. Additionally, FCs from the basal ganglia to the dorsolateral prefrontal cortex were found to be negatively correlated with originality in dancers., Discussion: Our results highlight the proficient communication within the cortical-subcortical hierarchy of the eMNS in dancers, linked to the automaticity and cognitive-motor interactions acquired through training. Altered functional couplings in the eMNS can be regarded as a unique neural signature specific to virtuoso dancers, which might predispose them for skilled dancing performance, perception, and creation., Competing Interests: 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., (Copyright © 2023 Yang, Yu, Hong, Shih, Yeh, Chen and Hsieh.)

Background: The lack of effective and accurate predictive indicators remains a major bottleneck for the improvement of the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Hepatitis B virus X (HBx) has been widely suggested as a critical pathogenic protein for HBV-driven liver carcinogenesis, while tumor-associated macrophage (TAM) infiltration is also closely related to the tumorigenesis and progression of HCC. However, few studies have determined whether combining HBx expression with TAM populations could increase the accuracy of prognostic prediction for HBV-related HCC., Methods: The study cohort enrolling 251 patients with HBV-related HCC was randomly split into a training and a validation group (ratio 1:1). The expression levels of HBx and TAM marker CD68 in HCC samples were detected by immunohistochemistry. Kaplan-Meier curves, Cox regression and Harrell's concordance index (C-index) analysis were conducted to evaluate the prognostic significance of these indicators alone or in combination., Results: The expression level of HBx was strongly correlated with CD68 + TAM infiltration in HCC tissues. Elevated HBx or CD68 expression indicated poorer overall survival (OS) and progression-free survival (PFS) after hepatectomy, and both of them were independent risk factors for postoperative survival. Meanwhile, patients with both high HBx and CD68 levels had worst clinical outcomes. Moreover, integrating HBx and CD68 expression with clinical indicators (tumor size and micro-vascular invasion) showed the best prognostic potential with highest C-index value for survival predictivity, and this proposed model also performed better than several conventional classifications of HCC., Conclusion: Combining the expression of intratumoral HBx, CD68 + TAM population and clinical variables could enable better prognostication for HBV-related HCC after hepatectomy, thus providing novel insights into developing more effective clinical prediction model based on both molecular phenotypes and tumor-immune microenvironment., (© 2023. The Author(s).)

Introduction: This study sought to elucidate the cognitive traits of visual artists (VAs) from the perspective of visual creativity and the visual system (i.e., the most fundamental neural correlate)., Methods: We examined the local and long-distance intrinsic functional connectivity (FC) of the visual system to unravel changes in brain traits among VAs. Twenty-seven university students majoring in visual arts and 27 non-artist controls were enrolled., Results: VAs presented enhanced local FC in the right superior parietal lobule, right precuneus, left inferior temporal gyrus (ITG), left superior parietal lobule, left angular gyrus, and left middle occipital gyrus. VAs also presented enhanced FC with the ITG that targeted the visual area (occipital gyrus and cuneus), which appears to be associated with visual creativity., Discussion: The visual creativity of VAs was correlated with strength of intrinsic functional connectivity in the visual system. Learning-induced neuroplasticity as a trait change observed in VAs can be attributed to the macroscopic consolidation of consociated neural circuits that are engaged over long-term training in the visual arts and aesthetic experience. The consolidated network can be regarded as virtuoso-specific neural fingerprint., Competing Interests: 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., (Copyright © 2023 Hong, Yang, Shih, Fan, Yeh, Yu, Chen and Hsieh.)

Numerous studies have reported that long-term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long-term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion-weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion-related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience-dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal-related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long-term musical training can strengthen or prune white matter connectivity networks in an experience-dependent manner., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The neurogenetic basis of variability in human olfactory function remains elusive. This study examined olfactory performance and resting-state functional neuroimaging results from healthy volunteers within the context of the brain-derived neurotrophic factor (BDNF) val66met polymorphism with the aim of unraveling the genotype-associated intrinsic reorganization of the olfactory network. We found that the presence of the Met allele is associated with better olfactory identification and additional engagement of semantic memory system within the olfactory network, in an allele dosage-dependent manner. This suggests that the Met allele may promote adaptive neural reorganization to augment olfactory capacity., (© 2022. The Author(s).)

Humor has been considered an effective emotion regulation strategy, and some behavioral studies have examined its superior effects on negative emotion regulation. However, its neural mechanisms remain unknown. Our functional magnetic resonance imaging study directly compared the emotion regulation effects and neural bases of humorous coping (reappraisal) and ordinary reappraisal following exposure to negative pictures. The behavioral results suggested that humorous reappraisal was more effective in downregulating negative emotions and upregulating positive emotions both in the short and long term. We also found 2 cooperative neural pathways involved in coping with negative stimuli by means of humor: the "hippocampal-thalamic-frontal pathway" and the "amygdala-cerebellar pathway." The former is associated with the restructuring of mental representations of negative situations and accompanied by an insightful ("Aha!") experience, while the latter is associated with humorous emotional release and accompanied by an expression of laughter ("Haha!"). Furthermore, the degree of hippocampal functional connectivity with both the thalamus and frontal cortex was positively correlated with changes in positive emotion, and this result implied that the degree of emotion regulation could be strongly directly related to the depth of cognitive reconstruction. These findings highlight that regulating negative emotions with humor involves cognitive restructuring and the release of positive emotions., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anode passivation is still a main challenge for the electrochemical generation of ferrate(VI, Fe(VI)), leading to the reduction of Fe(VI) production efficiency. In this study, cyclic voltammetry, scanning electronic microscopy, and electrochemical impedance spectroscopy were used to select better anode electrode configurations (iron wire, iron gauze, and iron coil). The results indicate that iron coil had the least degree of passivation. Different imposed current waveforms during the electrochemical generation of Fe(VI) were also investigated, and the iron coil imposed with square alternating current (AC) wave can mitigate the anode passivation, resulting in higher Fe(VI) production efficiency. The optimum conditions for the electrochemical generation of Fe(VI) were evaluated and the optimum temperature (40 ℃), current density (10 mA/cm 2 ), AC cycle period (15 s) and electrolyte concentrations (14 M NaOH) were identified. As a result, 0.12 mol/L Fe(VI) concentration and over 50% of current efficiency can be achieved after 3 h electrolysis. The generated Fe(VI) solution was further applied to oxidize doxycycline(DOX) and sulfadiazine(SDZ) as typical antibiotics. Over 80% of DOX can be removed at a Fe(VI) to DOX molar ratio of 5:1 (pH = 4-9), whilst a higher Fe(VI) to SDZ molar ratio of 20:1 (pH = 7) was needed to obtain 75% SDZ removal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia., Methods: A prospective study employing resting-state functional magnetic resonance imaging was conducted. Twelve sciatica patients were enrolled to receive six or 18 acupoints of acupuncture treatment twice a week for 4 weeks. Regional homogeneity (ReHo) and seed-based FC were performed., Results: Regional homogeneity analysis demonstrated a greater alteration in the right posterior cingulate cortex (PCC) during the pre-acupuncture phase than during the postacupuncture phase. Compared to that of healthy controls, the PCC-seeded FC (default mode network, DMN) of sciatica patients exhibited hyperconnectivity of PCC-FC with the PCC-bilateral insula, cerebellum, inferior parietal lobule, right medial prefrontal cortex, and dorsal anterior cingulate cortex during the pre-acupuncture phase as well as hypoconnectivity of PCC-FC with the right cerebellum, left precuneus, and left dorsal medial prefrontal cortex during the postacupuncture phase. Correlation analysis between PCC-seeded FC and behavior measurements revealed a positive association with the duration of sciatica in the right inferior parietal lobule prior to acupuncture treatment., Conclusions: Acupuncture in chronic sciatica patients is associated with normalized DMN activity and modulation of descending pain processing. The changes in the subclinical endophenotype of brain FC after acupuncture treatment may provide clues for understanding the mechanism of acupuncture-mediated analgesia in chronic pain., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

A cyclen-based hybrid supermolecule crystal, [(FeCl 2 )(cyclen)]Cl (1), where cyclen=1,4,7,10-tetraazacyclododecane, was prepared using a liquid-liquid diffusion approach. The variable crystal structures exhibit that compound 1 belongs to an orthorhombic crystal system, Pna2 1 space group (point group C 2V ) in the temperature range of 150-400 K. This hybrid supermolecule shows a dielectric relaxation behavior around room temperature, and the ferroelectric nature of 1 has been directly verified by hysteresis measurements. In addition, the AC (alternating current) conductivity study reveals that the 1 displays a beyond limiting behavior. These interesting findings are for the first time reported in the field of supermolecular ferroelectrics. This study may open a new way to construct supermolecular ferroelectrics and give insights into their conductor behavior., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: In the clinic, how to stratify renal cell carcinoma (RCC) patients with different risks and to accurately predict their prognostic outcome remains a crucial issue. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients., Methods: The expression of gankyrin was examined in public databases and validated in specimens from two independent centers. The clinical practice and disease correlation of gankyrin in RCC were evaluated in RCC patients, various cell lines and an orthotopic RCC model., Findings: Upregulation of gankyrin expression in RCC was corroborated in two independent cohorts. High gankyrin expression positively associated with disease progression and metastasis of RCC patients. A positive correlation between gankyrin and sunitinib-resistance was also observed in RCC cell lines and in an orthotopic RCC model. Kaplan-Meier analysis revealed that patients with higher gankyrin expression presented worse prognosis of RCC patients in the two cohorts. Gankyrin served as an independent prognostic factor for RCC patients even after multivariable adjustment by clinical variables. Time-dependent AUC and Harrell's c-index analysis presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Fuhrman nuclear grade or SSIGN score achieved a greater accuracy than without it in predicting prognosis of RCC patients. All results were confirmed in randomized training and validation sets from the two patient cohorts., Interpretation: Gankyrin can serve as a reliable biomarker for disease progression and for prognosis of RCC patients. Combining gankyrin with the current clinical parameters may help patient management. FUND: National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Medical Discipline Construction Project of Pudong New Area Commission of Health and Family Planning (PWYgf2018-03), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No. PWR12016-05)., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To compare the efficacy of new percutaneous technique ("ultra-mini PCNL", UMP), shock wave lithotripsy (SWL) and flexible ureteroscopy (FURS) on the treatment of 1-2 cm lower pole kidney stones, and to determine the advantages and disadvantages of each method., Materials and Methods: This prospective study was based on data collected from the files of patients between March 2015 and March 2017. This study recruited a total of 180 patients with single radio-opaque lower caliceal calculi of 1-2 cm. All patients were randomly divided into 3 groups: group A was treated with UMP, group B was treated with FURS by using holmium laser and group C was treated with SWL by using the electromagnetic lithotripter. The average age, sex, size of the stone, the time of operation, the rate of no stone, the time of hospitalization, the rate of retreatment, the cost and the complications of the 3 groups were compared. The success of the operation was defined as no residual stone or < 0.3 cm on computed tomography at 3 months postoperatively., Results: The stone burdens of the groups were equivalent. The re-treatment rate in group C was significantly higher than that in group A and B (30 vs. 1.6%, 5%). The average operating time in group B (93.35 ± 21.64 min) was statistically significantly longer than that in group A and C (68.58 ± 15.82 min, 46.33 ± 5.81 min). Although the time of hospitalization of group A (5.32 ± 1.20 day) was longer than that of group B (3.22 ± 0.52 day) and C (1.08 ± 0.28 day; p < 0.05). The stone-free rate (SFR) in UMP, FURS, SWL were 98, 92, and 73% respectively; the highest SFR was in the UMP group (p < 0.05). The complication rates were evaluated by using the Clavien grading system, which were determined to be 16.67% in UMP, 6.67% in SWL and 8.33% in FURS. In particular, the complications of GI and GII were more common in group A (p < 0.05)., Conclusions: UMP, FURS, and SWL are all safe and effective in the treatment of 1-2 cm lower pole kidney stones. UMP and FURS had a better SFR than SWL, but the time of hospitalization in UMP group was longer and there were more complications in the UMP group. In addition, the operation time of FURS is longer as compared to UMP and SWL, and there is a higher rate of postoperative fever. The invasiveness and cost of SWL were lower than that of UMP and FURS, but the re-treatment rate was higher., (© 2018 S. Karger AG, Basel.)

Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has shown promising therapeutic potential against diabetic cataracts, but whether this compound exerts beneficial effects on the other diabetic microvascular complications remains unclear. This study was carried out to examine effects of gigantol on high glucose-induced renal cell injury in cultured mouse kidney mesangial cells (MES-13). MES-13 cells were pretreated with gigantol (1, 5, 10 or 20 μmol/L) for 1 h followed by further exposure to high (33.3 mmol/L) glucose for 48 h. Gigantol concentration dependently enhanced cell viability followed by high glucose treatment in MES-13 cells. High glucose induced reactive oxygen species (ROS) generation, malondialdehyde production and glutathione deficiency were recoved in MES-13 cells pretreated with gigantol. High glucose triggered cell apoptosis via the the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by gigantol. High glucose also induced activation of JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in MES-13 cells, which were blocked by gigantol. The results suggest that treatment MES-13 cells with gigantol halts high glucose-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our data are of value to the understanding the mechanism for gigantol, and would benefit the study of drug development or food supplement for diabetes and nephropathy.

The present study aimed to determine whether hesperidin, a plant-based active flavanone found in citrus fruits, can prevent high glucose-induced retinal pigment epithelial (RPE) cell impairment. Cultured human RPE cells (ARPE-19) were exposed to a normal glucose concentration (5.5 mM) for 4 d and then soaked in either normal (5.5 mM) or high (33.3 mM) concentrations of D-glucose with or without different concentrations of hesperidin (10, 20, or 40 µM) for another 48 h. The survival rates of the cells were measured using a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay. With the help of a fluorescent probe, the intracellular production of reactive oxygen species (ROS) was evaluated. Colorimetric assay kits were used to assess the antioxidant enzyme activities, and western blotting was used to measure the expression of apoptosis-related protein. Hesperidin was effective in inhibiting high glucose-induced ROS production, preventing loss of cell viability, and promoting the endogenous antioxidant defense components, including glutathione peroxidase, superoxide dismutase, catalase, and glutathione, in a concentration-dependent manner. Furthermore, high glucose triggered cell apoptosis via the upregulation of caspase-9/3, enhancement of cytochrome c release into the cytosol, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by hesperidin in a concentration-dependent manner. We conclude that through the scavenging of ROS and modulation of the mitochondria-mediated apoptotic pathway, hesperidin may protect RPE cells from high glucose-induced injury and thus may be a candidate in preventing the visual impairment caused by diabetic retinopathy., Competing Interests: No competing financial interests exist., (Georg Thieme Verlag KG Stuttgart · New York.)

Multifunctional materials that exhibit different physical properties in a single phase have potential for use in multifunctional devices. Herein, we reported an organic-inorganic hybrid compound [(18-crown-6)K][Fe(1)Cl(1) 4 ] 0.5 [Fe(2)Cl(2) 4 ] 0.5 (1) by incorporating KCl and FeCl 3 into a 18-crown-6 molecule, which acts as a host of the six O atoms providing a lone pair of electrons to anchor the guest potassium cation, and [FeCl 4 ] - as a counterion for charge balance to construct a complex salt. This salt exhibited a one-step reversible structural transformation giving two separate high and low temperature phases at 373 K, which was confirmed by systematic characterizations including differential scanning calorimetry (DSC) measurements, variable-temperature structural analyses, and dielectric, impedance, variable-temperature magnetic susceptibility measurements. Interestingly, the structural transformation was coupled to both hysteretic dielectric phase transition, conductivity switch and magnetic-phase transition at 373 K. This result gives an idea for designing a new type of phase-transition materials harboring technologically important magnetic, conductivity and dielectric properties., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigate diosmin for its effect on the ARPE-19 human retinal pigment epithelial cells exposed to high glucose, a model of diabetic retinopathy (DR). After incubation for 4 days with a normal (5 mmol/L) concentration of D-glucose, ARPE-19 cells were exposed separately to normal or high concentrations of D-glucose (30 mmol/L) with or without diosmin at different concentrations (0.1, 1, 10 μg/mL) for another 48 h. Next, we assessed cell viability, reactive oxygen species (ROS) generation and antioxidant enzyme activities. In order to examine the underlying molecular mechanisms, we meanwhile analyzed the expressions of Bax, Bcl-2, total and phosphorylated JNK and p38 mitogen-activated protein kinase (MAPK). Diosmin dose dependently enhanced cell viability following high glucose treatment in ARPE-19 cells. The activities of superoxide dismutase and glutathione peroxidase, as well as the levels of reduced glutathione were decreased, while it was observed that levels of ROS in high glucose cultured ARPE-19 cells increased. High glucose also disturbed Bax and Bcl-2 expression, interrupted Bcl-2/Bax balance, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by diosmin. Furthermore, diosmin could abrogate high glucose-induced apoptosis as well as JNK and P38 MAPK phosphorylation in ARPE-19 cells. Our results suggest that treatment ARPE-19 cells with diosmin halts hyperglycemia-mediated oxidative damage and thus this compound may be a candidate for preventing the visual impairment caused by DR., Competing Interests: The authors declare no conflicts of interest in relation to this work.

The aim of this study was to investigate the protective effects and mechanisms of hesperidin, a plant based active flavanone found in citrus fruits, under the oxidative stress and apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs). RGC-5 cells were pretreated with hesperidin (12.5, 25, or 50 μmol/L) for 6 h followed by exposure to high (33.3 mmol/L) d-glucose for 48 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to evaluate cell viability. Mitochondrial function was estimated by measuring the mitochondrial membrane potential (ΔΨm). A fluorescent probe was employed to evaluate the intercellular production of reactive oxygen species (ROS). Colorimetric assay kits were used to evaluate lipid peroxidation, antioxidant enzyme activities, and protein carbonyls formation. The expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) were measured with Western blotting. Hesperidin inhibited high glucose-mediated cell loss and restored mitochondrial function including a reversion of ΔΨm loss and cytochrome c release. Treated with hesperidin, high glucose-induced increase in ROS, malondialdehyde, and protein carbonyl levels were blocked in RGC-5 cells. Hesperidin was found to elevate the activities of superoxide dismutase, catalase, glutathione peroxidase, and to recover glutathione levels. Hesperidin inhibited high glucose-induced cell apoptosis by attenuating the downregulation of caspase-9, caspase-3, and Bax/Bcl-2. Furthermore, the phosphorylation of c-Jun N-terminal kinases (JNK) and p38 MAPK triggered by high glucose were attenuated in RGC-5 cells after their incubation with hesperdin. We concluded that hesperidin may protect RGC-5 cells from high glucose-induced injury since it owns the properties of antioxidant action and blocks mitochondria-mediated apoptosis., Competing Interests: The authors declare no conflicts of interest in relation to this work.

Objective: The aim of the study was to compare the educational impact of two postsimulation debriefing methods-focused and corrective feedback (FCF) versus Structured and Supported Debriefing (SSD)-on team dynamics in simulation-based cardiac arrest team training., Methods: This was a pilot randomized controlled study conducted at a simulation center. Fourth-year medical students were randomly assigned to the FCF or SSD group, with each team composed of six students and a confederate. Each team participated in two simulations and the assigned debriefing (FCF or SSD) sessions and then underwent a test simulation. Two trained raters blindly assessed all of the recorded simulations using checklists. The primary outcome was the improvement in team dynamics scores between baseline and test simulation. The secondary outcomes were improvements before and after training in team clinical performance scores, self-assessed comprehension of and confidence in cardiac arrest management and team dynamics, as well as evaluations of the postsimulation debriefing intervention., Results: In total, 95 students participated [FCF (8 teams, n = 47) and SSD (8 teams, n = 48)]. The SSD team dynamics score during the test simulation was higher than at baseline [baseline: 74.5 (65.9-80.9), test: 85.0 (71.9-87.6), P = 0.035]. However, there were no differences in the improvement in the team dynamics or team clinical performance scores between the two groups (P = 0.328, respectively)., Conclusions: There was no significant difference in improvement in team dynamics scores during the test simulation compared with baseline between the SSD and FCF groups in a simulation-based cardiac arrest team training in fourth-year Korean medical students.

Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks. Oral administration of PSEE resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and retinal vascular permeability and leukostasis in diabetic rats. In addition, PSEE administration increased the activities of superoxidase dismutase (SOD) and catalase (CAT), and glutathione peroxidase (GSH) level in diabetic retinae. PSEE treatment inhibited the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) and the phosphorylation of Akt without altering the Akt protein expression in diabetic retinae. PSEE not only down-regulated the gene expression of hypoxia-inducible factor-1α (TNF-α) and interleukin-1β (IL-1β), but also reduced ICAM-1 and VCAM-1 expression in diabetic retinae. Moreover, PSEE reduced the nuclear factor-κB (NF-κB) activation and corrected imbalance between histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities in diabetic retinae. In conclusion, phenolic antioxidants extract from plantaginis semen has potential benefits in the prevention and/or progression of DR., Competing Interests: The authors declare no conflicts of interest in relation to this work.

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood-retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The present study investigates the amelioration of diabetic retinopathy (DR) by Zingiber zerumbet rhizome ethanol extracts (ZZRext) in streptozotocin-induced diabetic rats (STZ-diabetic rats). ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day) for three months. Blood-retinal barrier (BRB) breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB) activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK) in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.