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The microtubule-associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau's engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse-mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid-modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p-tau) present two-state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid-tau interaction. The results indicate that p-tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease., (© 2024 Wiley-VCH GmbH.)

Leucine is an essential amino acid for fish. The ability of leucine to resist stress in fish has not been reported. Nitrite is a common pollutant in the aquatic environment. Therefore, we investigated the effects of dietary leucine on growth performance and nitrite-induced liver damage, mitochondrial dysfunction, autophagy, and apoptosis for sub-adult grass carp. A total of 450 grass carp (615.91 ± 1.15 g) were selected and randomly placed into 18 net cages. The leucine contents of the six diets were 2.91, 5.90, 8.92, 11.91, 14.93, and 17.92 g/kg, respectively. After a 9-week feeding trial, the nitrite exposure experiment was set up for 96 h. These results indicated that dietary leucine significantly promoted FW, WG, PWG, and SGR of sub-adult grass carp (P < 0.05). Appropriate levels of dietary leucine (11.91-17.92 g/kg) decreased the activities of serum parameters (glucose, cortisol, and methemoglobin contents, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase), the contents of reactive oxygen species (ROS), nitric oxide (NO) and peroxynitrite (ONOO - ). In addition, appropriate levels of dietary leucine (11.91-17.92 g/kg) increased the mRNA levels of mitochondrial biogenesis genes (PGC-1α, Nrf1/2, TFAM), fusion-related genes (Opa1, Mfn1/2) (P < 0.05), and decreased the mRNA levels of caspase 3, caspase 8, caspase 9, fission-related gene (Drp1), mitophagy-related genes (Pink1, Parkin) and autophagy-related genes (Beclin1, Ulk1, Atg5, Atg7, Atg12) (P < 0.05). Appropriate levels of dietary leucine (8.92-17.92 g/kg) also increased the protein levels of AMP-activated protein kinase (AMPK), prostacyclin (p62) and decreased the protein levels of protein light chain 3 (LC3), E3 ubiquitin ligase (Parkin), and Cytochrome c (Cytc). Appropriate levels of leucine (8.92-17.92 g/kg) could promote growth performance and alleviate nitrite-induced mitochondrial dysfunction, autophagy, apoptosis for sub-adult grass carp. Based on quadratic regression analysis of PWG and serum GPT activity, dietary leucine requirements of sub-adult grass carp were recommended to be 12.47 g/kg diet and 12.55 g/kg diet, respectively., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the content of this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Electrocatalysis is considered promising in renewable energy conversion and storage, yet numerous efforts rely on catalyst design to advance catalytic activity. Herein, a hydrodynamic single-particle electrocatalysis methodology is developed by integrating collision electrochemistry and microfluidics to improve the activity of an electrocatalysis system. As a proof-of-concept, hydrogen evolution reaction (HER) is electrocatalyzed by individual palladium nanoparticles (Pd NPs), with the development of microchannel-based ultramicroelectrodes. The controlled laminar flow enables the precise delivery of Pd NPs to the electrode-electrolyte interface one by one. Compared to the diffusion condition, hydrodynamic collision improves the number of active sites on a given electrode by 2 orders of magnitude. Furthermore, forced convection enables the enhancement of proton mass transport, thereby increasing the electrocatalytic activity of each single Pd NP. It turns out that the improvement in mass transport increases the reaction rate of HER at individual Pd NPs, thus a phase transition without requiring a high overpotential. This study provides new avenues for enhancing electrocatalytic activity by altering operating conditions, beyond material design limitations.

Muscle is the main edible part of bony fish. The purpose of this study was to investigate the influences of phenylalanine (Phe) on muscle quality, amino acid composition, fatty acid composition, glucose metabolism, and protein deposition in adult grass carp. The diets at 2.30, 4.63, 7.51, 10.97, 13.53, and 17.07 g/kg Phe levels were fed for 9 weeks. The results manifested that Phe (10.97-13.53 g/kg) increased the pH of the fillets and decreased muscle cooking loss and lactic acid content; Phe (7.51-17.07 g/kg) improved the composition of the fillets in terms of flavor (free) amino acids, bound amino acids (especially EAA), and fatty acids (especially EPA and DHA); Phe (7.51-13.53 g/kg) increased muscle glycogen content (possibly related to the AMPK signaling pathway) and muscle protein deposition (possibly related to IGF-1/4EBP1/TOR and AKT/FOXOs signaling pathways). In conclusion, a diet with appropriate Phe levels could improve fillet quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Biomarkers are present in various metabolism processes, demanding precise and meticulous analysis at the single-molecule level for accurate clinical diagnosis. Given the need for high sensitivity, biological nanopore have been applied for single biomarker sensing. However, the detection of low-volume biomarkers poses challenges due to their low concentrations in dilute buffer solutions, as well as difficulty in parallel detection. Here, a droplet nanopore technique is developed for low-volume and high-throughput single biomarker detection at the sub-microliter scale, which shows a 2000-fold volume reduction compared to conventional setups. To prove the concept, this nanopore sensing platform not only enables multichannel recording but also significantly lowers the detection limit for various types of biomarkers such as angiotensin II, to 42 pg. This advancement enables direct biomarker detection at the picogram level. Such a leap forward in detection capability positions this nanopore sensing platform as a promising candidate for point-of-care testing of biomarker at single-molecule level, while substantially minimizing the need for sample dilution., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bacterial pathogens destroy the structural integrity of functional organs in fish, leading to severe challenges in the aquaculture industry. Vitamin D 3 (VD 3 ) prevents bacterial infections and strengthens immune system function via vitamin D receptor (VDR). However, the correlation between VD 3 /VDR and the structural integrity of functional organs remains unclarified. This study aimed to investigate the influence of VD 3 supplementation on histological characteristics, apoptosis, and tight junction characteristics in fish intestine during pathogen infection. A total of 540 healthy grass carp (257.24 ± 0.63 g) were fed different levels of VD 3 (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) for 70 d. Subsequently, fish were challenged with Aeromonas hydrophila , a pathogen that causes intestinal inflammation. Our present study demonstrated that optimal supplementation with VD 3 (1) alleviated intestinal structural damage, and inhibited oxidative damage by reducing levels of oxidative stress biomarkers; (2) attenuated excessive apoptosis-related death receptor and mitochondrial pathway processes in relation to p38 mitogen-activated protein kinase signaling ( P  < 0.05); (3) enhanced tight junction protein expression by inhibiting myosin light chain kinase signaling ( P  < 0.05); and (4) elevated VDR isoform expression in fish intestine ( P  < 0.05). Overall, the results demonstrated that VD 3 alleviates oxidative injury, apoptosis, and the destruction of tight junction protein under pathogenic infection, thereby strengthening pathogen defenses in the intestine. This finding supports the rationale for VD 3 intervention as an essential practice in sustainable aquaculture., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

To further explain the improvement effect of threonine (Thr) on the fillet quality of fish, a 9-week feeding experiment was conducted. After feeding graded levels of Thr (2.38, 5.38, 8.38, 11.38, 14.38 and 17.38 g/kg), the compositions of fillet hydrolyzed amino acid and fatty acid, and the muscle hardness associated with collagen biosynthesis were mainly analyzed in grass carp (Ctenopharyngodon idella). The results showed that Thr increased the pH value, changed the amino acids and fatty acid composition of fillets, especially essential amino acid (EAA), C22:6n3 (DHA) and C20:5n3 (EPA). Furthermore, this study revealed for the first time that the improvement of muscle hardness by Thr was associated with collagen biosynthesis, and the TGF-β1/Smads, LARP6a and Hsp47 regulate transcriptional processes, translation initiation and post-translational modifications in collagen biosynthesis, respectively. This study offered a basis for exploring the contribution of Thr in improving muscle quality in sub-adult grass carp., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Copper (Cu) is a trace element, essential for fish growth. In the current study, in addition to growth performance, we first explored the effects of Cu on collagen synthesis and myofiber growth and development in juvenile grass carp ( Ctenopharyngodon idella) . A total of 1080 fish (11.16 ± 0.01 g) were randomly divided into 6 treatments (3 replicates per treatment) to receive five doses of organic Cu, which were Cu citrate (CuCit) at 0.99 (basal diet), 2.19, 4.06, 6.15, and 8.07 mg/kg, and one dose of inorganic Cu (CuSO 4 ·5H 2 O at 3.15 mg/kg), for 9 weeks. The results showed appropriate Cu level (4.06 mg/kg) enhanced growth performance, improved nutritional Cu status, and downregulated Cu-transporting ATPase 1 mRNA levels in the hepatopancreas, intestine, and muscle of juvenile grass carp. Meanwhile, collagen content in fish muscle was increased after Cu intake, which was probably due to the following pathways: (1) activating CTGF/TGF-β1/Smads signaling pathway to regulate collagen transcription; (2) upregulating of La ribonucleoprotein domain family 6 ( LARP6) mRNA levels to regulate translation initiation; (3) increasing proline hydroxylase, lysine hydroxylase, and lysine oxidase activities to regulate posttranslational modifications. In addition, optimal Cu group increased myofiber diameters and the frequency of myofibers with diameter >50 μm, which might be associated with upregulation of cyclin B, cyclin D, cyclin E, proliferating cell nuclear antigen, myogenic determining factor (MyoD) , myogenic factor 5, myogenin ( MyoG) , myogenic regulatory factor 4 and myosin heavy chain ( MyHC) and downregulation of myostatin mRNA levels, increasing protein levels of MyoD, MyoG and MyHC in fish muscle. Finally, based on percentage weight gain (PWG), serum ceruloplasmin (Cp) activity and collagen content in fish muscle, Cu requirements were determined as 4.74, 4.37 and 4.62 mg/kg diet (CuCit as Cu source) of juvenile grass carp, respectively. Based on PWG and Cp activity, compared to CuSO 4 ·5H 2 O, the efficacy of CuCit were 131.80% and 115.38%, respectively. Our findings provide new insights into Cu supplementation to promote muscle growth in fish, and help improve the overall productivity of aquaculture., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

In recent years, mannose oligosaccharide (MOS) as a functional additive is widely used in aquaculture, to enhance fish immunity. An evaluation of the effect of dietary MOS supplementation on the immune barrier function and related signaling molecules mechanism of grass carp ( Ctenopharyngodon idella ) was undertaken in the present study. Six diets with graded amounts of MOS supplementation (0, 200, 400, 600, 800, and 1000 mg/kg) were fed to 540 grass carp over 60 days. To examine the immune response and potential mechanisms of MOS supplementation on the intestine, a challenge test was conducted using injections of Aeromonas hydrophila for 14 days. Results of the study on the optimal supplementation with MOS were found as follows (1) MOS enhances immunity partly related to increasing antibacterial substances content and antimicrobial peptides expression; (2) MOS attenuates inflammatory response partly related to regulating the dynamic balance of intestinal inflammatory cytokines; (3) MOS regulates immune barrier function may partly be related to modulating TLRs/MyD88/NFκB and TOR/S6K1/4EBP signalling pathways. Finally, the current study concluded that MOS supplementation could improve fish intestinal immune barrier function under Aeromonas hydrophila infected conditions., Competing Interests: Authors S-YK, LT, S-WL, C-BZ were employed by Sichuan Animtech Feed Co. Ltd. The remaining 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 © 2022 Lu, Feng, Jiang, Wu, Liu, Jiang, Kuang, Tang, Li, Zhong and Zhou.)

Electrochemical measurements at the single entity level provide ultra-sensitive tools for the precise diagnosis and understanding of basic biological and chemical processes. By decoding current signatures, single-entity electrochemistry provides abundant information on charges, sizes, shapes, catalytic performances and compositions. The accuracy of single-entity electrochemistry highly relies on advanced instrumentation to achieve the amperometric resolution at the sub-picoampere level and the temporal resolution at the sub-microsecond level. Currently, it is still a challenge for paralleling amplifiers to allow low-noise and high bandwidth single-entity electrochemical measurements. Herein, we developed a low-noise four-channel electrochemical instrumentation that integrates an Au electrode array with amplifiers in the circuit board. With this amplifier array, we achieved a high bandwidth (>100 kHz) electrochemical measurement. The further practical experiments proved the capability of this amplifier array system in acquiring transient signals from both single-molecule detection with an aerolysin nanopore and single Pt nanoparticle catalysis during the dynamic collision process. Paired with appropriate microfluidic array systems, our instrumentation will enable an extraordinarily high-throughput feature for single-entity sensing.

To clarify the discrete nature of electrochemistry, single-entity electrochemistry of collision (SEEC) utilizes a confinement space in a nanoscale local electric field at a microscale electrode interface for characterizing single freely diffusing entities. This promising method provides new insights at the single entity level. However, the precise measurement is challenging because of the short residence time and wide current fluctuations caused by the dynamic and stochastic motion of a single entity at the interface of the electrode. Moreover, the enormous noise in the electrochemical system would submerge these weak transient electrochemical signals. To increase the signal-to-noise ratio, the low-pass filter (LPF) is often used but at the cost of lower temporal resolution. Therefore, a deeper understanding of the filtering effects on the electrochemical signal is required in SEEC. Here, we build a random walk model to simulate the dynamic electrochemical oxidation of individual silver nanoparticles (AgNPs) in the local electric field near the electrode. This model considers the effect of the effective potential during the interaction between NP and electrode. Results reveal that the shape of the signal is seriously distorted as the cutoff frequency ( f c ) of LPF is set at <20 kHz. Due to the filtering effects, hundreds of subpeaks originating from the dynamic motion of NP are merged in a simple peak, which muddies our "believing" from the "seeing" signals. However, the entire interaction time of single NPs with the electrodes can be acquired at f c ≥ 10 kHz. Moreover, an integral charge of the signal is conserved at any LPF, which enables quantitative analysis of SEEC. Our understanding of the filtering effect on single AgNPs oxidation is generally applicable to nano-electrochemical techniques (e.g., nanopore electrochemistry and nanopipette sensing) that generate transient current signals., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Nanopore measurement has advanced in single-molecule analysis by providing a transient time and confined space window that only allows one interested molecule to exist. By optimization and integration of the electrical and optical analysis strategies in this transient window, the acquisition of comprehensive information could be achieved to resolve the intrinsic properties and heterogeneity of a single molecule. In this work, we present a roadmap to build a unified optical and electrochemical synchronous measurement platform for the research of a single molecule. We design a low-cost ultralow-current amplifier with low noise and high-bandwidth to measure the ionic current events as a single molecule translocates through a nanopore and combine a multi-functional optical system to implement the acquisition of the fluorescence, scattering spectrum, and photocurrent intensity of single molecule events in a nanopore confined space. Our system is a unified and unique platform for the protein nanopore, the solid-state nanopore, and the glass capillary nanopore, which has advantages in the comprehensive research of nanopore single-molecule techniques.

The objective of this study was to evaluate the efficacy of dietary Mannan oligosaccharides (MOS) supplementation on skin barrier function and the mechanism of on-growing grass carp ( Ctenopharyngodon idella ). Five hundred forty grass carp were fed for 60 days from the growing stage with six different levels of MOS diets (0, 200, 400, 600, 800, and 1,000 mg kg -1 ). At the end of the growth trial, the 14-day Aeromonas hydrophila challenge experiment has proceeded. The obtained data indicate that MOS could (1) decline skin lesion morbidity after being challenged by the pathogenic bacteria; (2) maintain physical barrier function via improving antioxidant ability, inhibiting excessive apoptosis, and strengthening the tight junction between the epithelial cell and the related signaling pathway (Nrf2/Keap1, p38MAPK, and MLCK); and (3) regulate immune barrier function by modulating the production of antimicrobial compound and expression of involved cytokines and the related signaling pathway (TOR and NFκB). Finally, we concluded that MOS supplementation reinforced the disease resistance and protected the fish skin barrier function from Aeromonas hydrophila infection., Competing Interests: S-YK, LT, S-WL, X-AL and C-BZ were employed by Sichuan Animtech Feed Co. Ltd. The remaining 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 © 2021 Lu, Feng, Jiang, Wu, Liu, Jiang, Kuang, Tang, Li, Liu, Zhong and Zhou.)

Nanopore electrochemistry, as one of the promising tools for single molecule sensing, has proved its capability in DNA sequencing and protein analysis. To achieve a high resolution for obtaining molecular information, the nanopore electrochemical technique not only urgently requires an appropriate nanopore sensing interface with atomic resolution but also requires advanced instrumentation and its related data processing methods. In order to reveal the fundamental biological process and process the point-of-care diagnosis, it is necessary to use a nanopore sensing instrument with a high amperometric and temporal resolution as well as high throughput. The development of the instrumentation requires multi-disciplinary collaboration involving preparing a sensitive nanopore interface, low-noise circuit design, and intelligent data analysis. In this review, we have summarized the recent improvements in the nanopore sensing interface as well as discussed the higher throughput achieved by nanopore arrays and intelligent nanopore data analysis methods. The parallelized nanopore instrumentation could be popularized to all ranges of single-molecule applications.

Melatonin is a pineal-produced indole known for its anti-aging, antiapoptotic and antioxidant properties. In past decades, the protective potentials of melatonin for cardiovascular diseases, such as atherosclerosis and myocardial infarction, have been widely revealed, triggering more investigations focused on other cardioprotective effects of melatonin. Recently, the roles of melatonin in diabetic cardiomyopathy (DCM) have attracted increased attention. In this regard, researchers found that melatonin attenuated cardiac fibrosis and hypertrophy, thus interrupting the development of DCM. Retinoid-related orphan receptor α is a key melatonin receptor that contributed to the cardioprotective effect of melatonin in hearts with DCM. For the downstream mechanisms, the inhibition of mammalian STE20-like kinase 1 plays a pivotal role, which exerts antiapoptotic and proautophagic effects, thus enhancing cardiac tolerance in high-glucose conditions. In addition, other signalling mechanisms, such as sirtuin-1/peroxisome proliferator-activated receptor gamma-coactivator alpha and endoplasmic reticulum-related signalling, are also involved in the protective effects of melatonin on cardiomyocytes under diabetic conditions. This review will focus on the protective signalling mechanisms regulated by melatonin and provide a better understanding of the therapeutic applications of melatonin signalling in DCM., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yan-Jun Song et al.)

Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia-reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress-inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis-related proteins) and signaling pathways (e.g., c-Jun N-terminal kinase pathway and extracellular-signal-regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning-induced HSP70 (e.g., hyperthermia preconditioning-induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70-mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review., (© 2018 Wiley Periodicals, Inc.)

We examined the psychological impact of visual darkness on people's perceived risk of contagious-disease transmission. We posited that darkness triggers an abstract construal level and increases perceived social distance from others, rendering threats from others to seem less relevant to the self. We found that participants staying in a dimly lit room (Studies 1 and 3-5) or wearing sunglasses (Study 2) tended to estimate a lower risk of catching contagious diseases from others than did those staying in a brightly lit room or wearing clear glasses. The effect persisted in both laboratory (Studies 1-4) and real-life settings (Study 5). The effect arises because visual darkness elevates perceived social distance from the contagion (Study 3) and is attenuated among abstract (vs. concrete) thinkers (Study 4). These findings delineate a systematic, unconscious influence of visual darkness-a subtle yet pervasive situational factor-on perceived risk of contagion. Theoretical contributions and policy implications are discussed.

Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury. Thus, this review focuses on the role of PPARγ in cardioprotection during myocardial I/R. The cardioprotective effects of PPARγ, including attenuating oxidative stress, inhibiting inflammatory responses, improving glucose and lipid metabolism, and antagonizing apoptosis, are described. Additionally, the underlying mechanisms of cardioprotective effects of PPARγ, such as regulating the expression of target genes, influencing other transcription factors, and modulating kinase signaling pathways, are further discussed.

The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.

We investigated whether the prevalence of fast-food restaurants in the social ecology are associated with greater financial impatience at the national, neighborhood, and individual level. Study 1 shows that the proliferation of fast-food restaurants over the past 3 decades in the developed world was associated with a historic shift in financial impatience, as manifested in precipitously declining household savings rates. Study 2 finds that households saved less when living in neighborhoods with a higher concentration of fast-food restaurants relative to full-service restaurants. With a direct measure of individuals' delay discounting preferences, Study 3 confirms that a higher concentration of fast-food restaurants within one's neighborhood is associated with greater financial impatience. In line with a causal relationship, Study 4 reveals that recalling a recent fast-food, as opposed to full-service, dining experience at restaurants within the same neighborhood induced greater delay discounting, which was mediated behaviorally by how quickly participants completed the recall task itself. Finally, Study 5 demonstrates that pedestrians walking down the same urban street exhibited greater delay discounting in their choice of financial reward if they were surveyed in front of a fast-food restaurant, compared to a full-service restaurant. Collectively, these data indicate a link between the prevalence of fast food and financial impatience across multiple levels of analysis, and suggest the plausibility of fast food having a reinforcing effect on financial impatience. The present investigation highlights how the pervasiveness of organizational cues in the everyday social ecology can have a far-ranging influence.

A pounding heart is a common symptom people experience when confronting moral dilemmas. The authors conducted 4 experiments using a false feedback paradigm to explore whether and when listening to a fast (vs. normal) heartbeat sound shaped ethical behavior. Study 1 found that perceived fast heartbeat increased volunteering for a just cause. Study 2 extended this effect to moral transgressions and showed that perceived fast heartbeat reduced lying for self-gain. Studies 3 and 4 explored the boundary conditions of this effect and found that perceived heartbeat had less influence on deception when people are mindful or approach the decision deliberatively. These findings suggest that the perceived physiological experience of fast heartbeats may signal greater distress in moral situations and hence motivate people to take the moral high road., (PsycINFO Database Record (c) 2013 APA, all rights reserved.)

Social power, alcohol intoxication, and anonymity all have strong influences on human cognition and behavior. However, the social consequences of each of these conditions can be diverse, sometimes producing prosocial outcomes and other times enabling antisocial behavior. We present a general model of disinhibition to explain how these seemingly contradictory effects emerge from a single underlying mechanism: The decreased salience of competing response options prevents activation of the Behavioral Inhibition System (BIS). As a result, the most salient response in any given situation is expressed, regardless of whether it has prosocial or antisocial consequences. We review three distinct routes through which power, alcohol intoxication, and anonymity reduce the salience of competing response options, namely, through Behavioral Approach System (BAS) activation, cognitive depletion, and reduced social desirability concerns. We further discuss how these states can both reveal and shape the person. Overall, our approach allows for multiple domain-specific models to be unified within a common conceptual framework that explains how both situational and dispositional factors can influence the expression of disinhibited behavior, producing both prosocial and antisocial outcomes., (© Association for Psychological Science 2011.)

Based on recent advancements in the behavioral priming literature, three experiments investigated how incidental exposure to fast food can induce impatient behaviors and choices outside of the eating domain. We found that even an unconscious exposure to fast-food symbols can automatically increase participants' reading speed when they are under no time pressure and that thinking about fast food increases preferences for time-saving products while there are potentially many other product dimensions to consider. More strikingly, we found that mere exposure to fast-food symbols reduced people's willingness to save and led them to prefer immediate gain over greater future return, ultimately harming their economic interest. Thus, the way people eat has far-reaching (often unconscious) influences on behaviors and choices unrelated to eating.

Consumer choices reflect not only price and quality preferences but also social and moral values, as witnessed in the remarkable growth of the global market for organic and environmentally friendly products. Building on recent research on behavioral priming and moral regulation, we found that mere exposure to green products and the purchase of such products lead to markedly different behavioral consequences. In line with the halo associated with green consumerism, results showed that people act more altruistically after mere exposure to green products than after mere exposure to conventional products. However, people act less altruistically and are more likely to cheat and steal after purchasing green products than after purchasing conventional products. Together, our studies show that consumption is connected to social and ethical behaviors more broadly across domains than previously thought.

Darkness can conceal identity and encourage moral transgressions; it may also induce a psychological feeling of illusory anonymity that disinhibits dishonest and self-interested behavior regardless of actual anonymity. Three experiments provided empirical evidence supporting this prediction. In Experiment 1, participants in a room with slightly dimmed lighting cheated more and thus earned more undeserved money than those in a well-lit room. In Experiment 2, participants wearing sunglasses behaved more selfishly than those wearing clear glasses. Finally, in Experiment 3, an illusory sense of anonymity mediated the relationship between darkness and self-interested behaviors. Across all three experiments, darkness had no bearing on actual anonymity, yet it still increased morally questionable behaviors. We suggest that the experience of darkness, even when subtle, may induce a sense of anonymity that is not proportionate to actual anonymity in a given situation.

Few interpersonal relationships endure without one party violating the other's expectations. Thus, the ability to build trust and to restore cooperation after a breach can be critical for the preservation of positive relationships. Using an iterated prisoner's dilemma, this article presents two experiments that investigated the effects of the timing of a trust breach-at the start of an interaction, after 5 trials, after 10 trials, or not at all. The findings indicate that getting off on the wrong foot has devastating long-term consequences. Although later breaches seemed to limit cooperation for only a short time, they still planted a seed of distrust that surfaced in the end.

Metaphors such as icy stare depict social exclusion using cold-related concepts; they are not to be taken literally and certainly do not imply reduced temperature. Two experiments, however, revealed that social exclusion literally feels cold. Experiment 1 found that participants who recalled a social exclusion experience gave lower estimates of room temperature than did participants who recalled an inclusion experience. In Experiment 2, social exclusion was directly induced through an on-line virtual interaction, and participants who were excluded reported greater desire for warm food and drink than did participants who were included. These findings are consistent with the embodied view of cognition and support the notion that social perception involves physical and perceptual content. The psychological experience of coldness not only aids understanding of social interaction, but also is an integral part of the experience of social exclusion.

Research has yielded weak empirical support for the idea that creative solutions may be discovered through unconscious thought, despite anecdotes to this effect. To understand this gap, we examined the effect of unconscious thought on two outcomes of a remote-association test (RAT): implicit accessibility and conscious reporting of answers. In Experiment 1, which used very difficult RAT items, a short period of unconscious thought (i.e., participants were distracted while holding the goal of solving the RAT items) increased the accessibility of RAT answers, but did not increase the number of correct answers compared with an equal duration of conscious thought or mere distraction. In Experiment 2, which used moderately difficult RAT items, unconscious thought led to a similar level of accessibility, but fewer correct answers, compared with conscious thought. These findings confirm and extend unconscious-thought theory by demonstrating that processes that increase the mental activation of correct solutions do not necessarily lead them into consciousness.

Individuals define themselves, at times, as who they are (e.g., a psychologist) and, at other times, as who they are not (e.g., not an economist). Drawing on social identity, optimal distinctiveness, and balance theories, four studies examined the nature of negational identity relative to affirmational identity. One study explored the conditions that increase negational identification and found that activating the need for distinctiveness increased the accessibility of negational identities. Three additional studies revealed that negational categorization increased outgroup derogation relative to affirmational categorization and the authors argue that this effect is at least partially due to a focus on contrasting the self from the outgroup under negational categorization. Consistent with this argument, outgroup derogation following negational categorization was mitigated when connections to similar others were highlighted. By distinguishing negational identity from affirmational identity, a more complete picture of collective identity and intergroup behavior can start to emerge.

Subtended angle has been assumed to be an important factor in both response programming time and kinematic characteristics of aiming movements. Support for this assumption has come mainly from studies in which circular targets have been used. However, with circular targets, the subtended angle covaries with the size of the target in the principal direction of the movement (tolerance width). The purpose of this study was to examine the effects of tolerance width and subtended angle on aiming movement with multiple targets. Participants first hit a 5-cm-diameter circular target located 8 cm to the left of a starting position and then moved another 8 cm left to hit either a 5-cm diameter circular target or a 5- x 1-cm rectangular target oriented either horizontally or vertically, depending on the condition. Analysis showed that reaction times and movement times were longer for the vertical rectangular target, which had a smaller tolerance width than the other two targets. In addition, the vertical rectangular target also showed a greater percentage of secondary-submovement trials, lower movement velocity, and higher peak vertical displacement. Overall, the results indicate that the tolerance width of the target may impose more constraints on aiming movements than subtended angle.

Physical cleansing has been a focal element in religious ceremonies for thousands of years. The prevalence of this practice suggests a psychological association between bodily purity and moral purity. In three studies, we explored what we call the "Macbeth effect"-that is, a threat to one's moral purity induces the need to cleanse oneself. This effect revealed itself through an increased mental accessibility of cleansing-related concepts, a greater desire for cleansing products, and a greater likelihood of taking antiseptic wipes. Furthermore, we showed that physical cleansing alleviates the upsetting consequences of unethical behavior and reduces threats to one's moral self-image. Daily hygiene routines such as washing hands, as simple and benign as they might seem, can deliver a powerful antidote to threatened morality, enabling people to truly wash away their sins.

Aim: To find new peroxisome proliferator-activated y agonists with high activity and low toxicity., Methods: Based on JTT-501 and JTT-20993, new isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds were designed and synthesized. Their insulin-sensitizing activities were evaluated., Results: Eight new compounds were obtained. The structures of synthesized compounds were characterized by NMR, MS and IR. Four compounds (1A-4A) showed insulin-sensitizing activities., Conclusion: Compounds (1A and 3A) showed excellent insulin-sensitizing activities and should be worth further investigation.

To explore the ionic mechanisms of memory deficits induced by cholinergic lesion, whole-cell patch clamp recording techniques in combination with single-cell RT-PCR were used to characterize delayed rectifier potassium currents (IK) in acutely isolated hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. Scopolamine could induce deficits in spatial memory of rats. The peak amplitude and current density of IK measured in hippocampal pyramidal neurons were increased from 1.2+/-0.6 nA and 38+/-19 pA/pF of the control group (n=12) to 1.8+/-0.5 nA and 62+/-24 pA/pF (n=48, P<0.01) of the scopolamine-treated group. The steady-state activation curve of IK was shifted about 8 mV (P<0.01) in the direction of hyperpolarization in scopolamine-treated rats. The mRNA level of Kv2.1 was increased (P<0.01) in the scopolamine-treated group, but there was no significant change of Kv1.5 mRNA level. The present study demonstrated for the first time that IK was enhanced significantly in hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. The increase of Kv2.1 mRNA expression in hippocampal pyramidal cells might be responsible for the enhancement of IK and could be the ionic basis of the memory deficits induced by scopolamine.

Aim: To investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex., Methods: Whole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons., Results: The slowly inactivating outward currents (IK) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the IK of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of IK were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 mumol.L-1)., Conclusion: At concentrations as low as 1 mumol.L-1, donepezil was found to block the IK in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.

Hantaviral antibodies were detected in the sera from Apodemus (A.) agrarius and A. peninsulae captured in Ningxia province, China by several different serological diagnostic methods. A total of 409 sera from rodent and insectivore species were collected in 1999 and examined by indirect immunofluorescent antibody assay (IFA). Among them, 19 of 191 (9.9%) sera of A. agrarius and 1 of 13 (7.7%) sera of A. peninsulae were positive for hantaviral antibodies. The other species (Rattus norvegicus, Mus musculus, Cricetulus triton, and Sorex cylindricauda) were negative. The reaction pattern of positive serum was characterized as scattered and granular virus antigens in the cytoplasm of hantavirus infected Vero E6 cells. Some of the A. agrarius sera positive for hantavirus were further examined by Western blotting (WB), enzyme-linked immunosorbent assay (ELISA), and the focus reduction neutralization test (FRNT). By WB, positive sera showed the same specific reaction pattern of baculovirus-expressed recombinant hantaviral nucleocapsid protein, as shown in hantavirus-immune serum. By ELISA, IFA-positive sera showed significantly higher optical densities (around 1.0) than the negative A. agrarius sera. Hantaan type hantavirus was neutralized with the positive sera. These results suggest that A. agrarius have hantavirus infection and may play a role as a reservoir animal for hantavirus in Ningxia Hui Autonomous Province, China.

Aim: To investigate the effects of hypercholesterolemia on functions of rat aorta and on gene expression of inward rectifier and ATP-sensitive potassium channels in aortic smooth muscle., Methods: Rats were treated with high-cholesterol emulsion ig for 2 weeks; the aortic rings with and without endothelium were prepared to examine the aortic contractile and relaxation responses; RT-PCR was used to observe the gene expression of inward rectifier and ATP-sensitive potassium channels., Results: Hypercholesterolemia damaged the endothelium-dependent vascular functions severely, but did not affect the endothelium-independent vascular functions; Kir6.2 mRNA expression was upregulated (P < 0.05) and Kir3.1 mRNA expression was downregulated markedly (P < 0.05) in hypercholesterolemic smooth muscle., Conclusion: Hypercholesterolemia altered the vascular functions and regulated gene expression levels of specific inward rectifier and ATP-sensitive potassium channel subtypes.