Single-Atom Verification of the Optimal Trade-Off between Speed and Cost in Shortcuts to Adiabaticity.

The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.

Energy-Conversion Device Using a Quantum Engine with the Work Medium of Two-Atom Entanglement.

Although entanglement is considered as an essential resource for quantum information processing, whether entanglement helps for energy conversion or output in the quantum regime is still lack of experimental witness. Here, we report on an energy-conversion device operating as a quantum engine with the working medium acted by two entangled ions confined in a harmonic potential. The two ions are entangled by virtually coupling to one of the vibrational modes shared by the two ions, and the quantum engine couples to a quantum load, which is another shared vibrational mode. We explore the energy conversion efficiency of the quantum engine and investigate the useful energy (i.e., the maximum extractable work) stored in the quantum load by tuning the two ions in different degrees of entanglement as well as detecting the change of the phonons in the load. Our observation provides, for the first time, quantitative evidence that entanglement fuels the useful energy produced by the quantum engine, but not helpful for the energy conversion efficiency. We consider that our results may be useful to the study of quantum batteries for which one of the most indexes is the maximum extractable energy.

Enhancement of Quantum Heat Engine by Encircling a Liouvillian Exceptional Point.

Quantum heat engines are expected to outperform the classical counterparts due to quantum coherences involved. Here we experimentally execute a single-ion quantum heat engine and demonstrate, for the first time, the dynamics and the enhanced performance of the heat engine originating from the Liouvillian exceptional points (LEPs). In addition to the topological effects related to LEPs, we focus on thermodynamic effects, which can be understood by the Landau-Zener-Stückelberg process under decoherence. We witness a positive net work from the quantum heat engine if the heat engine cycle dynamically encircles a LEP. Further investigation reveals that a larger net work is done when the system is operated closer to the LEP. We attribute the enhanced performance of the quantum heat engine to the Landau-Zener-Stückelberg process, enabled by the eigenenergy landscape in the vicinity of the LEP, and the exceptional point-induced topological transition. Therefore, our results open new possibilities toward LEP-enabled control of quantum heat engines and of thermodynamic processes in open quantum systems.

[Fuchs corneal endothelial dystrophy treated with Descemet's stripping without endothelial keratoplasty (DWEK): a case report].

A patient with chief complaint of bilateral progressive visual impairment was diagnosed with Fuchs corneal dystrophy (FECD) in both eyes, macular hole in the left eye, and intraocular lens eye in the right eye. After communication with the patient and his family, they agreed to receive Descemet's stripping without endothelial keratoplasty (DWEK) in the left eye. One year after the operation, the cornea of the left eye was transparent, and the central posterior elastic layer was missing about 4.0 mm diameter. The naked vision of left eye was 0.1, and the correction was not improved. It can be seen that DWEK surgery has a good therapeutic effect on patients with mild FECD.

DXA-measured visceral fat mass and lean body mass reflect abnormal metabolic phenotypes among some obese and nonobese Chinese children and adolescents.

BACKGROUND AND AIM: The exact constellation of body composition characteristics among metabolically unhealthy obese (MUO) and nonobese (MUNO) children and adolescents remains unclear. The purpose of this study was to identify the major body composition determinants of metabolically unhealthy phenotypes among Chinese children and adolescents. METHODS AND RESULTS: We used data from a cross-sectional survey in 2015 that included 1983 children and adolescents aged 6-18 years. Subjects were classified into two phenotypes based on a combination of body mass index (BMI) and metabolic syndrome components. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Among all boys and among adolescent boys, those with MUNO phenotypes displayed significantly higher indices of body composition except for fat mass (FM) percentage and trunk-to-legs FM ratio compared with the metabolically healthy nonobese phenotype (all P < 0.05). MUO individuals had higher arm FM, lean body mass (LBM), and trunk lean mass compared to metabolically healthy obese individuals (all P < 0.05). Visceral fat mass (VFM) and BMI were the major independent determinants of MUNO (VFM, 6- to 9-year-old boys, OR = 1.02, 95% CI = 1.00-1.03, P = 0.021; BMI, 6- to 9-year-old girls, OR = 1.90, 95% CI = 1.31-2.84, P = 0.001; and adolescent boys, OR = 1.34, 95% CI = 1.23-1.44, P < 0.001). LBM was the major independent predictor of MUO among adolescent boys (OR = 1.90, 95% CI = 1.03-1.17, P = 0.003). CONCLUSIONS: Among children and adolescents, the metabolically unhealthy phenotype was associated with excess of body composition, but with significant differences observed based on age and sex. VFM and LBM derived by DXA can predict the metabolically unhealthy phenotype effectively in specific sex and age groups.

Activation of PPARα by clofibrate sensitizes pancreatic cancer cells to radiation through the Wnt/ß-catenin pathway.

Radiotherapy is emerging as an important modality for the local control of pancreatic cancer, but pancreatic cancer cell radioresistance remains a serious concern. Peroxisome proliferator-activated receptor α (PPARα) is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. The clinical relevance of PPARα and its biological function in pancreatic cancer radiosensitivity have not been previously described. In this study, we examined PPARα expression in tissue samples of pancreatic cancer patients. We found significantly higher expression of PPARα in pancreatic cancer tissues than in tumor-adjacent tissues and that the PPARα expression level is inversely associated with higher overall patient survival rate. We further observed that PPARα activation by its agonist clofibrate sensitizes pancreatic cancer cells to radiation by modulating cell cycle progression and apoptosis in several pancreatic cancer cell lines. Small interfering RNA-mediated PPARα silencing and PPARα blockade by the antagonist GW6471 abolish the effect of clofibrate on radiosensitization. An in vivo study showed that PANC1 xenografts treated with clofibrate are more sensitive to radiation than untreated xenografts. mRNA profiling by microarray analysis revealed that the expression of PTPRZ1 and Wnt8a, two core components of the ß-catenin pathway, is downregulated by clofibrate. Chromatin immunoprecipitation analysis confirmed that clofibrate abrogates the binding of nuclear factor-κB to the PTPRZ1 and Wnt8a promoters, ultimately decreasing Wnt/ß-catenin signaling activity, which is associated with radiosensitivity. Overall, we demonstrate that PPARα is overexpressed in pancreatic cancer tissues and clofibrate-mediated PPARα activation sensitizes pancreatic cancer cells to radiation through the Wnt/ß-catenin pathway.

Plasma exosome microRNAs are indicative of breast cancer.

BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin. To our knowledge, circulating exosome microRNAs have not been well-evaluated as biomarkers for breast cancer diagnosis or monitoring. METHODS: Exosomes were collected from the conditioned media of human breast cancer cell lines, mouse plasma of patient-derived orthotopic xenograft models (PDX), and human plasma samples. Exosomes were verified by electron microscopy, nanoparticle tracking analysis, and western blot. Cellular and exosome microRNAs from breast cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome microRNA expression was analyzed by qRT-PCR analysis. RESULTS: Small RNA sequencing and qRT-PCR analysis showed that several microRNAs are selectively encapsulated or highly enriched in breast cancer exosomes. Importantly, the selectively enriched exosome microRNA, human miR-1246, was detected at significantly higher levels in exosomes isolated from PDX mouse plasma, indicating that tumor exosome microRNAs are released into the circulation and can serve as plasma biomarkers for breast cancer. This observation was extended to human plasma samples where miR-1246 and miR-21 were detected at significantly higher levels in the plasma exosomes of 16 patients with breast cancer as compared to the plasma exosomes of healthy control subjects. Receiver operating characteristic curve analysis indicated that the combination of plasma exosome miR-1246 and miR-21 is a better indicator of breast cancer than their individual levels. CONCLUSIONS: Our results demonstrate that certain microRNA species, such as miR-21 and miR-1246, are selectively enriched in human breast cancer exosomes and significantly elevated in the plasma of patients with breast cancer. These findings indicate a potential new strategy to selectively analyze plasma breast cancer microRNAs indicative of the presence of breast cancer.

Hypertension outcomes in metabolically unhealthy normal-weight and metabolically healthy obese children and adolescents.

Metabolically healthy obesity (MHO) begins in childhood and continues into adulthood. However, the association between MHO and the risk of developing hypertension remains controversial. A prospective cohort study was conducted to investigate the risk of hypertension in MHO and metabolically unhealthy normal-weight (MUNW) Chinese children and adolescents. A total of 1183 participants, 6-18 years old at baseline with normal blood pressure values, were studied using follow-up data from the cohort of the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. The participants were classified according to the body mass index and the presence/absence of metabolic abnormality, which was defined by metabolic syndrome (MetS) or insulin resistance (IR). During the 6-year follow-up period, 239 (20.2%) participants developed incident hypertension. After adjusting for age, sex, physical activity, pubertal stage, dietary habits and family history of hypertension, an increased risk for hypertension was observed in the MHO individuals (risk ratio, RRMetS 5.42; 95% confidence interval (CI) 3.19-9.22 and RRIR 7.59; 95% CI 1.64-35.20) compared with their metabolically healthy normal-weight counterparts. Independent of the definition of metabolic abnormality, the MUNW subjects did not have an elevated incidence of hypertension. These results suggest that the risk of developing hypertension is increased in the MHO but not in the MUNW individuals.

Glucose and forskolin regulate IAPP gene expression through different signal transduction pathways.

Molecular mechanisms for the regulation of islet amyloid polypeptide (IAPP) gene expression remain unclear. In the present study, we investigated the effects of glucose and forskolin on IAPP gene regulation in the INS-1 islet beta-cell line. Both glucose and forskolin increased the level of expression of this gene, as measured by Northern blot analysis, and increased IAPP gene transcription in a time- and concentration-dependent manner, as demonstrated in a reporter gene assay. Although inhibition of protein kinase A activity with H-89 eliminated the effect of forskolin on this gene, the glucose effect was unaffected. This supported the predominant use of a protein kinase A-independent signaling pathway for glucose regulation of the IAPP gene. Electrophoretic mobility shift assay further indicated that glucose and forskolin regulated expression of this gene by targeting different elements of the promoter. Mutation of the cAMP regulatory element flanking the IAPP coding region resulted in the loss of most of the forskolin-stimulated IAPP gene promoter activity, whereas glucose-enhanced IAPP gene transcription was unaffected. These results demonstrate parallel and distinct regulatory pathways involved in glucose- and forskolin-induced IAPP gene expression in this model beta-cell system.

Receptor biology and signal transduction.

This year has witnessed substantial advances in receptor biology and signal transduction that are relevant to the function and regulation of the healthy pancreas and to the pathogenesis and potential therapy of pancreatitis and pancreatic carcinoma. There has been an expansion in the cast of pancreatic regulatory molecules, now including protease-activated receptors, chemokines, and chemokine receptors. There have been new insights into the cellular distribution and signaling initiated at the classic pancreatic receptors. There have also been dramatic advances in insights into the structure of G protein-coupled receptors, with the first solution of a crystal structure of a member of this superfamily, and into the molecular basis of ligand binding and activation of these important molecules. This will clearly improve the opportunities for the rational design and refinement of receptor-active drugs. In addition to these fundamental advances, there has been renewed attention to the expression, function, and regulation of receptors and signaling pathways in pancreatic cells present in the setting of pancreatitis and pancreatic carcinoma. It is hoped that this will contribute toward earlier diagnosis, more successful therapy, and new chemopreventive strategies for these illnesses.

Stimulation of muscarinic receptors induces expression of individual fos and jun genes through different transduction pathways.

The transduction pathways coupling muscarinic receptors to induction of fos and jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced expression of c-fos, fosB, c-jun, junB, and junD. This effect was abolished by pretreatment with atropine, indicating an involvement of muscarinic receptors. These genes were also induced by activation of protein kinase C with phorbol ester or by elevating the intracellular Ca2+ concentration with a Ca2+ ionophore. The Ca2+ effect was inhibited by KN-62, suggesting an induction through Ca2+/calmodulin-dependent kinase II. Inhibition of protein kinase C with GF109203X suppressed the carbachol-stimulated increase in mRNA levels of c-fos, fosB, and junB by approximately 70% but had only minor effects on the expression of c-jun and junD. On the other hand, preincubation with KN-62 attenuated the carbachol-induced increase in c-jun and junD expression by 70% but had no effect on c-fos, fosB, and junB mRNA levels. Simultaneous inhibition of both protein kinase C and Ca2+/calmodulin-dependent kinase II completely abolished the carbachol-stimulated expression of c-jun and junD, but c-fos, fosB, and junB were still expressed to a certain extent under this condition. Comparison of the inhibitory effects of GF109203X and Gö 6976 suggests the involvement of classical protein kinase C isozymes in muscarinic receptor-stimulated expression of fos and jun genes. These results demonstrate that the muscarinic receptor-induced expression of individual fos and jun genes is regulated via different pathways, primarily protein kinase C or Ca2+/calmodulin-dependent kinase II.

Ethanol exposure potentiates fosB and junB expression induced by muscarinic receptor stimulation in neuroblastoma SH-SY5Y cells.

Muscarinic receptor stimulation and activation of protein kinase C cause an increase in fosB and junB transcripts in human neuroblastoma SH-SY5Y cells. In this study, the effect of long-term ethanol exposure on these events was investigated. Carbachol-stimulated fosB and junB expression was elevated in ethanol-exposed cells compared with control cells. The potentiation was time- and dose-dependent on ethanol. Preincubation with muscarinic antagonists or protein kinase C inhibitor demonstrated that the carbachol-stimulated increase in fosB and junB mRNA levels was primarily mediated via M1 receptors and dependent on the activity of protein kinase C in both control and ethanol-exposed cells. Long-term ethanol exposure did not influence the expression of fosB and junB induced by activation of protein kinase C with phorbol ester. These results demonstrate that the muscarinic receptor-stimulated fosB and junB expression is sensitive to ethanol exposure in SH-SY5Y cells, suggesting that these genes participate in the regulation of neuronal function in response to chronic ethanol treatment.

Acute ethanol exposure attenuates expression of junD in human neuroblastoma cells.

This study describes the effects of acute ethanol exposure on the mRNA levels of c-jun,junB and junD in the human neuroblastoma SH-SY5Y cell line. An acute exposure to 100 mM ethanol did not influence the basal and phorbol ester-induced expression of c-jun and junB, whereas the basal mRNA level of junD was attenuated by 30%. This effect was dose- and time-dependent with maximal inhibition being detected 2 h after 100 mM ethanol treatment and the mRNA levels gradually returned towards normal afterwards. Ethanol also inhibited phorbol ester-induced expression of junD. The fact that ethanol did not influence degradation of the junD mRNA suggests that acute ethanol suppresses the transcription of the gene. These results indicate that acute ethanol exerts different effects on expression of Jun transcription factors, suggesting that as compared to c-jun and junB, the junD gene may be more sensitive to acute ethanol treatment in neuronal cells.

Effects of ethanol on muscarinic receptor-stimulated c-fos expression in human neuroblastoma cells.

The effect of ethanol exposure on muscarinic receptor-stimulated expression of c-fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced carbachol-stimulated c-fos mRNA expression, analyzed with Northern blot, and Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre-incubation with muscarinic antagonists or the protein kinase C inhibitor GF109203X demonstrated that, in both control and ethanol-treated cells, carbachol-induced c-fos expression was mediated via muscarinic M1 receptors and to a large extent through protein kinase C. However, phorbol ester-induced c-fos expression was unaffected in ethanol-treated cells. Acute exposure to ethanol caused a suppression of both carbachol- and phorbol ester-stimulated c-fos expression. These results demonstrate that muscarinic receptor-stimulated gene expression is sensitive to both acute and long-term ethanol exposure.

Ethanol exposure increases expression of c-jun and junD in human neuroblastoma cells.

The aim of this study was to investigate the effect of ethanol exposure on the expression of fos and jun genes. Exposure of human neuroblastoma SH-SY5Y cells to ethanol for 2-4 days caused a dose-dependent increase in c-jun and junD mRNA levels, whereas mRNAs for c-fos, fosB and junB were not detectable in control or ethanol-treated cells. Four days of ethanol exposure also enhanced the AP-1 binding activity. Experiments with actinomycin D demonstrated that ethanol did not influence the degradation of c-jun and junD mRNAs. These results demonstrate that long-term exposure to ethanol increases c-jun and junD expression. This effect may be one of the mechanisms through which ethanol influences the gene regulatory system in neuronal cells.