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Chinese cities are pursuing an energy transition to decouple energy-related carbon emissions (ERCEs) from economic growth. Despite numerous studies focusing on the factors influencing carbon emissions, few have quantitatively analyzed their respective contribution rates, thus leaving a gap in effectively guiding policies. This study took 16 cities in the Yangtze River Delta (YRD) as the study area. The decoupling between ERCEs and economic growth was analyzed during 2000–2020, and the contribution rates of different factors were explored. The results showed that the total ERCEs increased from 413.40 million to 1265.86 million tons during 2000–2020, increasing by over three times. Coal and oil were the dominant energy sources in most cities, but natural gas consumption increased from 0.15% to 5.96%. Moreover, 14 cities showed a decoupling status, indicating a certain win–win situation between economic growth and ERCE reduction. Economic growth greatly increased ERCEs, with its contribution rate ranging from 114.65% to 493.27% during 2000–2020. On the contrary, energy structure and energy intensity both contributed to reducing ERCEs in most cities, and their maximum contribution rates reached −32.29% and −449.13%, respectively, which were the main forces for the win–win situation. Finally, carbon reduction proposals are put forward, which provide theoretical support for achieving the "Double Carbon" goal in the YRD. [ABSTRACT FROM AUTHOR]

In this paper, we developed a fluorescent aptasensor for 17β-estradiol (E2) determination in aqueous solution using label-free E2-specific aptamer, gold nanoparticles (AuNPs) and Rhodamine B (RhoB) as sensing probe, fluorescent quencher and fluorescent indicator respectively. In the absence of E2, AuNPs were wrapped by E2 aptamer and maintained dispersed in NaCl solution basically. These dispersed AuNPs could effectively impair the originally high fluorescence of RhoB. Contrarily, in the presence of E2, E2 aptamer could specifically combine with E2 to form E2-aptamer complex, so the AuNPs were released by E2 aptamer and aggregated under the influence of NaCl. The aggregated AuNPs have a weak influence on RhoB fluorescence. Therefore, the E2 concentration can be determined by the change of fluorescence intensity of RhoB. This fluorescent assay has a detection limit as low as 0.48 nM, a linear range from 0.48 to 200 nM, and high selectivity over other disrupting chemicals. It was applied to determine E2 in water samples with recoveries in the range of 94.3–111.7%. The fluorescent aptasensor holds great potential for E2 detection in environmental water samples. [ABSTRACT FROM AUTHOR]

To explore the developmental toxicity of cefixime (CE) in the developmental disorder and toxicity mechanism of CE on otic vesicles, zebrafish embryos were used as an animal model. The results showed that CE increased mortality in a dose-dependent manner and decreased the hatching rate of zebrafish larva at 96 hpf. Interestingly, CE significantly reduced the area of the saccule and utricle, as well as the area of otic vesicles in zebrafish larvae (p < 0.001). Fibroblast growth factor 8a (Fgf8a) inhibitors and bone morphogenetic protein (BMP) inhibitors caused similar morphological changes. CE decreased the lateral hair cells of zebrafish larvae in a dose-dependent manner. Furthermore, CE caused the downregulation of cartilage and bone-related genes and Na+/K+-ATPase-related genes of zebrafish larvae at 72 hpf and 120 hpf according to RT-qPCR. A comparison with the control group revealed that 100 μg/mL CE also caused a decrease in Na+/K+-ATPase activity (p < 0.01). In addition, antibody staining verified that CE inhibited the expression of Na+/K+-ATPase in the otic vesicles and the nephridium of zebrafish larvae. The data obtained in this study suggested that CE has significant ototoxicity during embryonic development of zebrafish, which is closely related to Na+/K+-ATPase and the regulation of the Fgf8a / BMP signaling pathways. The effects and toxicity of CE on ear development in other animal models need to be further explored. [Display omitted] • Cefixime inhibited the development of zebrafish otic vesicles. • Cefixime reduced the neuromasts cells of zebrafish larvae. • Cefixime down-regulated Na+/K+-ATPase and bone development-related genes. • Cefixime reduced the expression of Na+/K+-ATPase activity and protein expression. [ABSTRACT FROM AUTHOR]

We investigate the dynamics of light rays in two classes of optical metamaterial systems: (1) time-dependent system with a volcano-shaped, inhomogeneous and isotropic refractive-index distribution, subject to external electromagnetic perturbations and (2) time-independent system consisting of three overlapping or non-overlapping refractive-index distributions. Utilizing a mechanical-optical analogy and coordinate transformation, the wave-propagation problem governed by the Maxwell's equations can be modeled by a set of ordinary differential equations for light rays. We find that transient chaotic dynamics, hyperbolic or nonhyperbolic, are common in optical metamaterial systems. Due to the analogy between light-ray dynamics in metamaterials and the motion of light in matter as described by general relativity, our results reinforce the recent idea that chaos in gravitational systems can be observed and studied in laboratory experiments. [ABSTRACT FROM AUTHOR]

Microscopic models based on evolutionary games on spatially extended scales have recently been developed to address the fundamental issue of species coexistence. In this pursuit almost all existing works focus on the relevant dynamical behaviors originated from a single but physically reasonable initial condition. To gain comprehensive and global insights into the dynamics of coexistence, here we explore the basins of coexistence and extinction and investigate how they evolve as a basic parameter of the system is varied. Our model is cyclic competitions among three species as described by the classical rock-paper-scissors game, and we consider both discrete lattice and continuous space, incorporating species mobility and intraspecific competitions. Our results reveal that, for all cases considered, a basin of coexistence always emerges and persists in a substantial part of the parameter space, indicating that coexistence is a robust phenomenon. Factors such as intraspecific competition can, in fact, promote coexistence by facilitating the emergence of the coexistence basin. In addition, we find that the extinction basins can exhibit quite complex structures in terms of the convergence time toward the final state for different initial conditions. We have also developed models based on partial differential equations, which yield basin structures that are in good agreement with those from microscopic stochastic simulations. To understand the origin and emergence of the observed complicated basin structures is challenging at the present due to the extremely high dimensional nature of the underlying dynamical system. [ABSTRACT FROM AUTHOR]

Scour prediction is essential for the design of offshore foundation structures. In this study, we experimentally investigate the clear-water scour around pile groups of the circular arrangement, with uniform bed sediment and steady current. Five pile-group arrangements and two flow velocities are considered. We illustrate the scouring process around each arrangement and derive the equilibrium scour depth. Based on our experimental results as well as previously published data, we check the accuracy of three widely-used empirical methods in predicting equilibrium scour depth of pile groups. It is found that, based on the effective diameter calculated for a rectangular arrangement, the predictions of all the selected methods lead to significant overestimation. Here, we propose a new effective diameter to represent the characteristic geometry of a circular arrangement. Essentially the projected width of a pile group is calculated by the diameter of a monopile that has the same cross-sectional area of the pile group. Using the new effective diameter, the predictions from the selected empirical methods are remarkably improved. • Circular arrangement pile groups are studied through experimental investigations. • A new effective diameter is proposed to represent such foundations′characteristic. • Three empirical methods for estimating equilibrium scour depth are evaluated. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to summarize the current evidence-based approach to perioperative enteral nutritional (EN) program for gastric cancer (GC) surgery and to develop a staged and operable EN management scheme based on the evidence to provide clinical guidance for improving perioperative EN management in patients with GC. Methods: First, we synthesized expert consensuses, systematic reviews, and guidelines related to GC patients who had undergone surgery, based on a review of the literature and expert meetings. Subsequently, after carefully evaluating and selecting relevant EN management data, we created a preliminary draft of a perioperative EN program. Following Delphi expert consultations, the final version of the perioperative EN program was constructed after revision. Results: After two rounds of consultation, the expert opinions tended to be consistent. The expert positive coefficient was 1.00, and the expert authority coefficient was 0.90. After the second round of consultation, the coefficient of variation of the importance score ranged from 0.05 to 0.20, and the coefficient of variation of the feasibility score ranged from 0.09 to 0.23. The Kendall harmony coefficients were 0.338 and 0.392, and the difference between them was statistically significant (p < 0.001). The final practice plan includes 4 first-level, 16 s-level, and 64 third-level items. Conclusions: The perioperative EN program constructed in this study is comprehensive in content, feasible, and evidence-based, and can provide insights for clinical improvement. [ABSTRACT FROM AUTHOR]

InSAR (Interferometric Synthetic Aperture Radar) is widely recognized as a crucial remote sensing tool for monitoring various geological disasters because it provides all-day and all-weather monitoring. Nevertheless, the current interpretation methods for InSAR heavily depend on the interpreter's experience, which hinders efficiency and fails to meet the requirements for the timely detection of geologic hazards. Furthermore, the results obtained through current InSAR processing carry inherent noise interference, further complicating the interpretation process. To address those issues, this paper proposes an approach that enables automatic and rapid identification of deformation zones. The proposed method leverages IPTA (Interferometric Point Target Analysis) technology for SAR data processing. It combines the power of HNSW (Hierarchical Navigable Small Word) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) algorithms to cluster deformation results. Compared with traditional methods, the computational efficiency of the proposed method is improved by 11.26 times, and spatial noise is suppressed. Additionally, the clustering results are fused with slope units determined using DEM (Digital Elevation Model), which facilitates the automatic identification of slopes experiencing deformation. The experimental verification in the western mountainous area of Beijing has identified 716 hidden danger areas, and this method is superior to the traditional technology in speed and automation. [ABSTRACT FROM AUTHOR]

Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations. Quantitative real-time PCR (qRT-PCR) and western blotting indicated that hiHeps highly expressed BA synthases and functional transporters. Liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that hiHeps produced normal intercellular unconjugated BAs but fewer conjugated BAs than human hepatocytes. When incubated with representative cholestatic agents, hiHeps exhibited sensitive drug-induced bile salt export pump (BSEP) dysfunction, and their response to cholestatic agent-mediated cytotoxicity correlated well with that of PHHs (r2 = 0.8032). Deoxycholic acid (DCA)-induced hepatotoxicity in hiHeps was verified by elevated aspartate aminotransferase (AST) and γ-glutamyl-transferase (γ-GT) levels. Mitochondrial damage and cell death suggested DCA-induced toxicity in hiHeps, which were attenuated by hepatoprotective drugs, as in PHHs. For the first time, hiHeps were reported to biosynthesize and excrete BAs, which could facilitate predicting cholestatic hepatotoxicity and screening potential therapeutic drugs against cholestasis. [ABSTRACT FROM AUTHOR]

Branched wave structures, an unconventional wave propagation pattern, can arise in random media. Experimental evidence has accumulated, revealing the occurrence of these waves in systems ranging from microwave and optical systems to solid-state devices. Experiments have also established the universal feature that the wave-intensity statistics deviate from Gaussian and typically possess a long-tail distribution, implying the existence of spatially localized regions with extraordinarily high intensity concentration ('hot' spots). Despite previous efforts, the origin of branched wave pattern is currently an issue of debate. Recently, we proposed a 'minimal' model of wave propagation and scattering in optical media, taking into account the essential physics for generating robust branched flows: (1) a finite-size medium for linear wave propagation and (2) random scatterers whose refractive indices deviate continuously from that of the background medium. Here we provide extensive numerical evidence and a comprehensive analytic treatment of the scaling behavior to establish that branched wave patterns can emerge as a general phenomenon in wide parameter regime in between the weak-scattering limit and Anderson localization. The basic physical mechanisms to form branched waves are breakup of waves by a single scatterer and constructive interference of broken waves from multiple scatterers. Despite simplicity of our model, analysis of the scattering field naturally yields an algebraic (power-law) statistic in the high wave-intensity distribution, indicating that our model is able to capture the generic physical origin of these special wave patterns. The insights so obtained can be used to better understand the origin of complex extreme wave patterns, whose occurrences can have significant impact on the performance of the underlying physical systems or devices. [ABSTRACT FROM AUTHOR]

This study aimed to explore behavioral changes of embryonic and larval zebrafish caused by pseudoephedrine hydrochloride (PSE) and its underlying mechanism. Zebrafish embryos were exposed to 0.5 µM, 2 µM, and 8 µM PSE at 4 h post-fertilization (4 hpf) or 22–23 hpf. Mortality, hatching rate, coiling frequency, heart rate, behavior changes, and related gene expression were observed at different developmental stages. PSE below 8 µM did not affect zebrafish mortality, hatching rate, and heart rate compared with the control group. For embryos, PSE caused an increase at 16–32 hpf in zebrafish coiling frequency which could be rescued by serotonin antagonist WAY100635. Similarly, PSE caused an increase in the swimming distance of zebrafish larvae at 120 hpf. PSE also elevated the expression of serotonin (5-HT)-related genes 5-htr1ab and tph2 and dopamine-related gene dbh. Behavioral changes in zebrafish embryos and larvae caused by PSE may be closely associated with increased expression of 5-HT and dopamine-related genes. This may be reflected that the behavioral changes in zebrafish are a possible PSE monitoring indicator. [ABSTRACT FROM AUTHOR]

The rapid development of digital image processing technology and the popularization of image editors have made computer-generated images more realistic so that it is more challenging to distinguish computer-generated images from natural images with the naked eye. Simultaneously, the malicious potential of highly realistic computer-generated images has made the detection of the authenticity of digital images a significant research area. In this work, we propose a computer-generated image detection algorithm through the application of transfer learning and Convolutional Block Attention Module. More specifically, our method uses the feature transfer module and feature fusion module to consider both the shallow content features and the deep semantic features of the image, thereby improving the accuracy of identifying computer-generated images. We validate our method through extensive experiments on various datasets, and the experimental results show that our model outperformed state-of-the-art methods and achieved an accuracy of 0.963. We also show that the proposed model has strong robustness and high generalization ability. [ABSTRACT FROM AUTHOR]

Background: Endothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear. Methods: Our study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model. Results: We found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked. Conclusions: The inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis. [ABSTRACT FROM AUTHOR]

Aims Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human-induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Methods and results Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro , thus presenting a promising approach for disease modelling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time. Conclusions In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases have consistently been one of the leading causes of mortality, despite investigations by many scientists and clinicians. Animal models are versatile platforms to illustrate various mechanisms of different diseases, but are lacking in accurately portraying cardiovascular disease phenotypes. The advent of human pluripotent stem cells (PSCs) has led to much development in the construction of cardiovascular disease models. In this review, we provide a brief overview of the history and utilization of PSCs for cardiovascular precision medicine, including disease modeling, drug screening, and gene editing, and elaborate on the current updated research status of patient-specific induced pluripotent stem cell (iPSC)-based disease models for cardiac channelopathies, cardiomyopathies, and other cardiovascular diseases. Furthermore, we highlight the development of novel human iPSC-derived engineered heart tissues for cardiovascular disease modeling. Finally, we put forward our own views on the existing advantages and difficulties for moving forward in this field. [ABSTRACT FROM AUTHOR]

Psoraleae Fructus is a well-known Traditional Chinese Medicine which has long been used to warm and tonify the kidney and treat diseases such as osteoporosis and diarrhea. However, it may cause multiorgan injury, which limited its use. The aim of this study was to identify the components of ethanol extract of salt-processed Psoraleae Fructus (EEPF) and systematically investigate its acute oral toxicity and the mechanism underlying its acute hepatotoxicity. In this study, the UHPLC-HRMS analysis was carried out for components identification. Followed by acute oral toxicity test in Kunming mice, which received oral gavage of EEPF from 3.85 to 78.00 g/kg. Body weight, organ indexes, biochemical analysis, morphology, histopathology, oxidative stress state, TUNEL, mRNA and protein expression of NLRP3/ASC/Caspase-1/GSDMD signaling pathway were evaluated to study the EEPF-induced acute hepatotoxicity and its underlying mechanisms. The results showed that 107 compounds such as psoralen and isopsoralen were identified in EEPF. And the acute oral toxicity test demonstrated the LD 50 of EEPF was 15.95 g/kg in Kunming mice. The survival mice displayed non-significant difference in body weight compared with Control at the end of the observation period. And the organ indexes of heart, liver, spleen, lung, and kidney showed no significant difference. However, the morphological and histopathological changes of these organs in high-dose-groups mice indicated that the liver and kidney might be the main target toxic organs of EEPF, which showed hepatocyte degeneration with lipid droplets and protein cast in kidney. It could be confirmed by the significant increases of liver and kidney function parameters such as AST, ALT, LDH, BUN, and Crea. In addition, the oxidative stress markers, MDA in the liver and kidney was significantly increased while SOD, CAT, GSH-Px (only liver), and GSH were significantly decreased. Furthermore, EEPF increased the TUNEL-positive cells and the mRNA and protein expression of NLRP3, Caspase-1, ASC and GSDMD in liver with increased protein expression of IL-1β and IL-18. Notably, cell viability test showed that the specific inhibitor of Caspase-1 could reverse the Hep-G2 cell death induced by EEPF. To summarize, this study analyzed the 107 compounds of EEPF. The acute oral toxicity test demonstrated the LD 50 value of EEPF was 15.95 g/kg in Kunming mice and the liver and kidney might be the main target toxic organs of EEPF. It caused liver injury through oxidative stress and pyroptotic damage via NLRP3/ASC/Caspase-1/GSDMD signaling pathway. [Display omitted] • In UHPLC-HRMS analysis, 107 compounds were identified in EEPF. • In acute oral toxicity test, the LD 50 value of EEPF was 15.95 g/kg in Kunming mice. • Liver and kidney might be the main target toxic organs of EEPF. • EEPF induced hepatoxicity through oxidative stress and pyroptotic damage. • Specific inhibitor of Caspase-1could reverse the Hep-G2 cell death induced by EEPF. [ABSTRACT FROM AUTHOR]

Wave forces on different pile-supported structures in regular and irregular waves are investigated experimentally. As a new characteristic geometric scale, an effective diameter is proposed to analyze the dimensionless total wave forces. With the effective diameter, unified empirical formulas describing the dimensionless wave forces versus Keulegan-Carpenter ( KC ) number are obtained for different complex pile-supported structures in regular and irregular waves. [ABSTRACT FROM AUTHOR]

This paper proposes an aptasensor for progesterone (P4) detection in human serum and urine based on the aggregating behavior of gold nanoparticles (AuNPs) controlled by the interactions among P4-binding aptamer, target P4 and cationic surfactant hexadecyltrimethylammonium bromide (CTAB). The aptamer can form an aptamer-P4 complex with P4, leaving CTAB free to aggregate AuNPs in this aptasensor. Thus, the sensing solution will turn from red (520 nm) to blue (650 nm) in the presence of P4 because P4 aptamers are used up firstly owing to the formation of an aptamer-P4 complex, leaving CTAB free to aggregate AuNPs. However, in the absence of P4, CTAB combines with aptamers so that AuNPs still remain dispersed. Therefore, this assay makes it possible to detect P4 not only by absorbance measurement but also through naked eyes. By monitoring the variation of absorbance and color, a CTAB-induced colorimetric assay for P4 detection was established with a detection limit of 0.89 nM. Besides, the absorbance ratio A 650/ A 520 has a linear correlation with the P4 concentration of 0.89–500 nM. Due to the excellent recoveries in serum and urine, this biosensor has great potential with respect to the visual and instrumental detection of P4 in biological fluids. [ABSTRACT FROM AUTHOR]

The authors describe an aptasensor for the detection of the gonadal hormone progesterone (P4) in aqueous solution. Gold nanoparticles (AuNPs) were coated with a P4-specific aptamer, and such particles do not aggregate in presence of NaCl due to the presence of the aptamer coating. If, however, progesterone is added, it will bind to the aptamer and release it from the surface. The uncoated AuNPs, on addition of NaCl, will aggregate and a color change from red (520 nm) to blue (650 nm) can be visually detected or photometrically quantified. The ratio of the absorbances at 650 and 520 nm is linearly related to the P4 concentration in the range from 2.6 to 800 nM. The complete detection range extends from 2.6 to 1400 nM, and the detection limit is 2.6 nM. Water containing various potential interferents, as well as tap water and urine, were spiked with P4 and the recoveries of P4 are in the range of 89.7-117.5%, 84.4-115.0% and 94.7-118.8%, respectively. This assay has a large potential with respect to the visual and instrumental determination of P4 in aquatic environment and urine. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

1. The purpose of this study was to investigate the mechanism of hepatic uptake of berberine. Berberine accumulation in hepatocytes was found to be highly dependent on active uptake, which could not be explained by liver organic cation transporter (OCT) alone. 2. Our studies indicated that berberine uptake was significantly suppressed by rifampicin, cyclosporine A and glycyrrhizic acid, which act as specific inhibitors of different Oatp isoforms (Oatp1a1, Oatp1a4 and Oatp1b2) in rat hepatocytes. The combination of OCT and OATP inhibitors further reduced berberine accumulation in both rat and human hepatocytes. The uptake of berberine could be increased in human HEK293-OATP1B3 but not in OATP1B1-transfected HEK 293 cells. 3. Rifampicin could reduce the berberine liver extraction ratio (ER) and double its concentration in the effluent in isolated rat livers. Furtherin vivostudy indicated that berberine plasma exposure could be significantly increased by co-administration of the OATP inhibitor rifampicin or the substrate rosuvastatin. 4. In conclusion, this study demonstrated that both OCT and OATP contribute to the accumulation of berberine in the liver. OATPs may have important roles in berberine liver disposition and potential clinically relevant drug--drug interactions. [ABSTRACT FROM AUTHOR]

Abstract: We study the formation of multi-armed spirals and multi-pairs antispirals in spatial rock–paper–scissors games with mobile individuals. We discover a set of seed distributions of species, which is able to produce multi-armed spirals and multi-pairs antispirals with a finite number of arms and pairs based on stochastic processes. The joint spiral waves are also predicted by a theoretical model based on partial differential equations associated with specific initial conditions. The spatial entropy of patterns is introduced to differentiate the multi-armed spirals and multi-pairs antispirals. For the given mobility, the spatial entropy of multi-armed spirals is higher than that of single armed spirals. The stability of the waves is explored with respect to individual mobility. Particularly, we find that both two armed spirals and one pair antispirals transform to the single armed spirals. Furthermore, multi-armed spirals and multi-pairs antispirals are relatively stable for intermediate mobility. The joint spirals with lower numbers of arms and pairs are relatively more stable than those with higher numbers of arms and pairs. In addition, comparing to large amount of previous work, we employ the no flux boundary conditions which enables quantitative studies of pattern formation and stability in the system of stochastic interactions in the absence of excitable media. [Copyright &y& Elsevier]

• Both S-muscone and R-muscone were acutely toxic to zebrafish embryonic heart. • Cardiotoxicity is partly related to increased Myh6 and Myh7 expression. • Muscone toxicity is related to thyroid hormone dysregulation. • R-muscone showed higher toxicity than S-muscone. Musk compounds are often used as to treat heart-related diseases and are widely used in Asia. Muscone is one of the most important physiologically active compounds of natural musk. Muscone is a chiral compound and can be further classified into S-muscone and R-muscone and both are present in synthetic musk. While these two chiral isomers have significant differences in odor properties, their difference in toxicity is still unknown. This study used zebrafish as an animal model to compare cardiac toxicities of S-muscone and R-muscone. Results showed that both compounds were acutely toxic to zebrafish embryos causing mortality, decreased hatching rate, pericardial edema, and decreased heart beat rate. These toxicities were modulated through increased Myh6 and Myh7 mRNA expression, and decreased thyroid genes (Trh, Thrβ, and Dio3) expression. R-muscone caused higher toxicity than S-muscone at the same concentration. For safety, the chiral isomer composition of synthetic muscone should be carefully regulated in the future. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart diseases are still a threat to human health. Human pluripotent stem cell-based transplantation exhibits great promise in cardiovascular disease therapy, including heart ischemia. The purpose of this study was to compare the efficacy of human embryonic stem cell-derived cardiomyocyte (ESC-CM) therapy in two heart ischemia models, namely, permanent ischemia (PI) and myocardial ischemia reperfusion (IR). Methods: Human embryonic stem cell-derived cardiomyocytes were differentiated from engineered human embryonic stem cells (ESC-Rep) carrying green fluorescent protein (GFP), herpes simplex virus-1 thymidine kinase (HSVtk), and firefly luciferase (Fluc). Two different heart ischemia models were generated by the ligation of the left anterior descending artery (LAD), and ESC-Rep-derived cardiomyocytes (ESC-Rep-CMs) were transplanted into the mouse hearts. Cardiac function was analyzed to evaluate the outcomes of ESC-Rep-CM transplantation. Bioluminescence signal analysis was performed to assess the cell engraftment. Finally, the inflammation response was analyzed by real-time PCR and ELISA. Results: Cardiac function was significantly improved in the PI group with ESC-Rep-CM injection compared to the PBS-injected control, as indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), as well as reduced fibrotic area. However, minimal improvement by ESC-Rep-CM injection was detected in the IR mouse model. We observed similar engraftment efficiency between PI and IR groups after ESC-Rep-CM injection. However, the restricted inflammation was observed after the injection of ESC-Rep-CMs in the PI group, but not in the IR group. Transplantation of ESC-Rep-CMs can partially preserve the heart function via regulating the inflammation response in the PI model, while little improvement of cardiac function in the IR model may be due to the less dynamic inflammation response by the mild heart damage. Conclusions: Our findings identified the anti-inflammatory effect of ESC-CMs as a possible therapeutic mechanism to improve cardiac function in the ischemic heart. [ABSTRACT FROM AUTHOR]