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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]

Access to birth registration among the refugees, migrants, and undocumented or stateless individuals in Sabah and Peninsular Malaysia remains hindered largely due to their lack of legal status. This study identifies the barriers to birth registration faced by these communities, including during the COVID-19 pandemic, and explores the extent to which digital technologies may overcome or amplify these barriers. Findings are reported from a review of literature, websites, and media articles and semi-structured interviews with community-based organisations and community leaders representing the communities. The themes for the questions were structured based on Plan International's (2015) Step-by-step Guide for Identifying and Addressing the Risks to Children in Digitised birth registration systems. We identified that the digitalisation of birth registration poses more risks of exclusion than benefits to the marginalised communities without a secure and inclusive operating environment. Subject to an inequality assessment to evaluate and address the existing inequalities, a hybrid system that factors in the role of citizen facilitation hubs would be ideal for ensuring no one gets “left behind”.

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]

Ship resistance increases significantly when navigating a brash ice channel. In this study, the numerical method is applied to predict the full-scale ship resistance of bulk carriers in brash ice channels. The viscous flow computational fluid dynamics (CFD) solver was coupled with the discrete element method (DEM) to establish the brash ice model. The Euler multiphase flow's volume of fluid (VOF) model was applied to simulate the interaction between the ship and water. The ship–brash ice interaction was simulated. Predictions of ships' total resistance based on the numerical method and the Finnish Swedish ice class rules (FSICR) method were compared with the experimental results carried out in Hamburg Ship Model Basin (HSVA) ice tank. The numerical resistance shows a good agreement with the HSVA experiment reports and a better performance than the FSICR method. The present study shows that the numerical method could provide reasonable and practical ice resistance predictions for engineering applications. [ABSTRACT FROM AUTHOR]

Borneol is an example of traditional Chinese medicine widely used in Asia. There are different isomers of chiral borneol in the market, but its toxicity and effects need further study. In this study, we used zebrafish embryos to examine the effects of exposure to three isomers of borneol [(−)‐borneol, (+)‐borneol, and isoborneol] on heart development and the association with Na+/K+‐ATPase from 4 h post‐fertilization (4 hpf). The results showed that the three isomers of borneol increased mortality and decreased hatching rate when the zebrafish embryo developed to 72 hpf. All three isomers of borneol (0.01–1.0 mM) significantly reduced heart rate from 48 to 120 hpf and reduced the expression of genes related to Ca2+‐ATPase (cacna1ab and cacna1da) and Na+/K+‐ATPase (atp1b2b, atp1a3b, and atp1a2). At the same time, the three isomers of borneol significantly reduced the activities of Ca2+‐ATPase and Na+/K+‐ATPase at 0.1 to 1.0 mM. (+)‐Borneol caused the most significant reduction (p < 0.05), followed by isoborneol and (−)‐borneol. Na+/K+‐ATPase was mainly expressed in otic vesicles and protonephridium. All three isomers of borneol reduced Na+/K+‐ATPase mRNA expression, but isoborneol was the most significant (p < 0.01). Our results indicated that (+)‐borneol was the least toxic of the three isomers while the isoborneol showed the most substantial toxic effect, closely related to effects on Na+/K+‐ATPase. This study used zebrafish embryos as an animal model to examine the effects of three borneol isomers [(−)‐borneol, (+)‐borneol, and isoborneol] on cardiac development. The results showed that all three isomers caused a decrease in heart rate, which may be related to the reduction of Na+/K+‐ATPase and Ca2+‐ATPase activities and decreased gene expression levels by borneol. The experimental results demonstrated that the toxicity caused by isoborneol was the largest, while the toxicity caused by (+)‐borneol was the least. [ABSTRACT FROM AUTHOR]

Computer-generated (CG) images have become indistinguishable from natural images due to powerful image rendering technology. Fake CG images have brought huge troubles to news media, judicial forensics, and other fields. How to detect CG image has become a key point to solve the problems mentioned above. The image classification method based on deep learning, due to its strong self-learning ability, can automatically determine the differences in the image features between CG images and natural images and can be used to detect CG images. However, deep learning often requires a large amount of labeled data, which is usually a tedious and complex task. This paper proposes an improved self-training strategy with fine-tuning teacher/student exchange (FTTSE) to solve the problem of missing labeled datasets. Our method is actually a strategy based on semisupervised learning to train the teacher model through labeled data and to predict the unlabeled data by the teacher model to generate pseudo labels. The student model is obtained by continuous training on the mixed dataset composed of labeled and pseudo-labeled data. A teacher/student exchange strategy is designed for iterative training; i.e., the identities of the teacher model and the student model are exchanged at the beginning of each round of iteration. And then the new teacher model is used to predict pseudo labels, and the new student model exchanged from teacher model in the previous round of iteration is fine-tuned and retrained by the mixed dataset with new pseudo labels. Furthermore, we introduced malicious image attacks to perturb the mixed dataset to improve the robustness of the student model. The experimental results show that the improved self-training model we proposed can stably maintain the image classification ability even if the testing images are maliciously attacked. After iterative training, the CG image detection accuracy of the final model increases by 5.18%. The robustness against 100% malicious attacks is also improved, where the final trained model has an accuracy improvement of 7.63% higher than the initial model. The self-training model with FTTSE strategy proposed in this paper can effectively enhance the detection ability of the existing model and can greatly improve the robustness of the model with iterative training. [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]

Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester‐diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 μM) increased frequency of coiling behavior in zebrafish embryos in a dose‐dependent manner and this effect can be triggered by either exposure to 5‐hydroxytryptamine 1A (5‐HT1A) receptor agonist (±)‐8‐hydroxy‐2‐(dipropylamino)tetralin (8‐OH‐DPAT) or overexpression of serotonin receptor 5‐htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co‐exposure to 5‐HT1A receptor antagonist WAY‐100635 Maleate (WAY100635) and knockdown of 5‐htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5‐htr1ab and 5‐htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5‐HT receptor. Aconitine increased frequency of coiling behavior in zebrafish embryos and this effect can be triggered by either exposure to 5‐HT1A receptor agonist 8‐OH‐DPAT or overexpression of serotonin receptor 5‐htr1ab. [ABSTRACT FROM AUTHOR]

Extensive experimental evidence has been demonstrated that the dynamics of CDK1‐APC feedback loop play crucial roles in regulating cell cycle processes, but the dynamical mechanisms underlying the regulation of this loop are still not completely understood. Here, the authors systematically investigated the stability and bifurcation criteria for a delayed CDK1‐APC feedback loop. They showed that the maximum reaction rate of CDK1 inactivation by APC can drive sustained oscillations of CDK1 activity (CDK1∗) and APC activity (APC∗), and the amplitude of these oscillations is increasing with the increase of the reaction rate over a wide range; a certain range of the self‐activation rate for CDK1 is also significant for generating these oscillations, for too high or too low rates the oscillations cannot be generated. Moreover, they derived the sufficient conditions to determine the stability and Hopf bifurcations, and found that the sum of time delays required for activating CDK1 and APC can induce CDK1∗ and APC∗ to be oscillatory, even when the CDK1∗ and APC∗ settle in a definite stable steady state. Furthermore, they presented an explicit algorithm for the properties of periodic oscillations. Finally, numerical simulations have been presented to justify the validity of theoretical analysis. [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]

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]

Aim:To investigate the mechanisms underlying the hepatotoxicity of timosaponin A3 (TA3), a steroidal saponin from Anemarrhena asphodeloides, in rats.Methods:Male SD rats were administered TA3 (100 mg·kg−1·d−1, po) for 14 d, and the blood and bile samples were collected after the final administration. The viability of a sandwich configuration of cultured rat hepatocytes (SCRHs) was assessed using WST-1. Accumulation and biliary excretion index (BEI) of d8-TCA in SCRHs were determined with LC-MS/MS. RT-PCR and Western blot were used to analyze the expression of relevant genes and proteins. ROS and ATP levels, and mitochondrial membrane potential (MMP) were measured. F-actin cytoskeletal integrity was assessed under confocal microscopy.Results:TA3 administration in rats significantly elevated the total bile acid in serum, and decreased bile acid (BA) component concentrations in bile. TA3 inhibited the viability of the SCRHs with an IC50 value of 15.21±1.73 μmol/L. Treatment of the SCRHs with TA3 (1-10 μmol/L) for 2 and 24 h dose-dependently decreased the accumulation and BEI of d8-TCA. The TA3 treatment dose-dependently decreased the expression of BA transporters Ntcp, Bsep and Mrp2, and BA biosynthesis related Cyp7a1 in hepatocytes. Furthermore, the TA3 treatment dose-dependently increased ROS generation and HO-1 expression, decreased the ATP level and MMP, and disrupted F-actin in the SCRHs. NAC (5 mmol/L) significantly ameliorated TA3-induced effects in the SCRHs, whereas mangiferin (10-200 μg/mL) almost blocked TA3-induced ROS generation.Conclusion:TA3 triggers liver injury through inducing ROS generation and suppressing the expression of BA transporters. Mangiferin, an active component in Anemarrhena, may protect hepatocytes from TA3-induced hepatotoxicity. [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 foundations. Several methods have been proposed to predict the equilibrium scour depth for monopiles. By introducing an effective diameter, such methods could also be applied to predicting scour depth for pile groups. Yet, there are still difficulties in estimating the equilibrium scour depth of foundations in complex shapes, such as the tripod foundation. This study investigates the clear-water scour around the tripod and hexapod foundations through laboratory experiments, with uniform bed sediment and steady current. Here, the authors propose an approach to calculate the effective diameter for the tripod and hexapod models, which is similarly as for the pile groups. Three widely-used methods in predicting equilibrium scour depth have been evaluated, and the best method is recommended. [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]

Critical adsorption controls translocation of polymer chains through lipid bilayers and permeation of solvent Giant negative group time delay by microwave mode adaptors A high intensity 6He beam for the β-beam neutrino oscillation facility Effect of chaos on relativistic quantum tunneling [ABSTRACT FROM AUTHOR]

We solve the Dirac equation in two spatial dimensions in the setting of resonant tunneling, where the system consists of two symmetric cavities connected by a finite potential barrier. The shape of the cavities can be chosen to yield both regular and chaotic dynamics in the classical limit. We find that certain pointer states about classical periodic orbits can exist, which suppress quantum tunneling, and the effect becomes less severe as the underlying classical dynamics in the cavity is chaotic, leading to regularization of tunneling dynamics even in the relativistic quantum regime. Similar phenomena have been observed in graphene. A physical theory is developed to explain the phenomenon based on the spectrum of complex eigenenergies of the non-Hermitian Hamiltonian describing the effectively open cavity system. [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]

• 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]

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage., Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT., Results: The study recruited a total of 490 patients, of whom 13.3% ( n  = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p  < 0.001). The overall mortality was 41.8% ( n  = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p  < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754)., Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Yang, Shi, Ni, Fan, Xu, Ma, Yang, Wang, Zi, Yang and Hao.)

Cancer cells largely rely on aerobic glycolysis or the Warburg effect to generate essential biomolecules and energy for their rapid growth. The key modulators in glycolysis including glucose transporters and enzymes, e.g. hexokinase 2, enolase 1, pyruvate kinase M2, lactate dehydrogenase A, play indispensable roles in glucose uptake, glucose consumption, ATP generation, lactate production, etc. Transcriptional regulation and post-translational modifications (PTMs) of these critical modulators are important for signal transduction and metabolic reprogramming in the glycolytic pathway, which can provide energy advantages to cancer cell growth. In this review we recapitulate the recent advances in research on glycolytic modulators of cancer cells and analyze the strategies targeting these vital modulators including small-molecule inhibitors and microRNAs (miRNAs) for targeted cancer therapy. We focus on the regulation of the glycolytic pathway at the transcription level (e.g., hypoxia-inducible factor 1, c-MYC, p53, sine oculis homeobox homolog 1, N 6 -methyladenosine modification) and PTMs (including phosphorylation, methylation, acetylation, ubiquitination, etc.) of the key regulators in these processes. This review will provide a comprehensive understanding of the regulation of the key modulators in the glycolytic pathway and might shed light on the targeted cancer therapy at different molecular levels., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe 2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe 2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc - -GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity., (© 2024 John Wiley & Sons Ltd.)

Borneol is an example of traditional Chinese medicine widely used in Asia. There are different isomers of chiral borneol in the market, but its toxicity and effects need further study. In this study, we used zebrafish embryos to examine the effects of exposure to three isomers of borneol [(-)-borneol, (+)-borneol, and isoborneol] on heart development and the association with Na + /K + -ATPase from 4 h post-fertilization (4 hpf). The results showed that the three isomers of borneol increased mortality and decreased hatching rate when the zebrafish embryo developed to 72 hpf. All three isomers of borneol (0.01-1.0 mM) significantly reduced heart rate from 48 to 120 hpf and reduced the expression of genes related to Ca 2+ -ATPase (cacna1ab and cacna1da) and Na + /K + -ATPase (atp1b2b, atp1a3b, and atp1a2). At the same time, the three isomers of borneol significantly reduced the activities of Ca 2+ -ATPase and Na + /K + -ATPase at 0.1 to 1.0 mM. (+)-Borneol caused the most significant reduction (p < 0.05), followed by isoborneol and (-)-borneol. Na + /K + -ATPase was mainly expressed in otic vesicles and protonephridium. All three isomers of borneol reduced Na + /K + -ATPase mRNA expression, but isoborneol was the most significant (p < 0.01). Our results indicated that (+)-borneol was the least toxic of the three isomers while the isoborneol showed the most substantial toxic effect, closely related to effects on Na + /K + -ATPase., (© 2022 John Wiley & Sons Ltd.)

Previous studies have shown that attention influences audiovisual integration (AVI) in multiple stages, but it remains unclear how AVI interacts with attentional load. In addition, while aging has been associated with sensory-functional decline, little is known about how older individuals integrate cross-modal information under attentional load. To investigate these issues twenty older adults and 20 younger adults were recruited to conduct a dual task including a multiple object tracking (MOT) task, which manipulated sustained visual attentional load, and an audiovisual discrimination task, which assesses AVI. The results showed that response times were shorter and hit rate was higher for audiovisual stimuli than for auditory or visual stimuli alone and in younger adults than in older adults. The race model analysis showed that AVI was higher under the load&#95;3 condition (monitoring two targets of the MOT task) than under any other load condition (no-load [NL], one or three targets monitoring). This effect was found regardless of age. However, AVI was lower in older adults than younger adults under NL condition. Moreover, the peak latency was longer, and the time window of AVI was delayed in older adults compared to younger adults under all conditions. These results suggest that slight visual sustained attentional load increased AVI but that heavy visual sustained attentional load decreased AVI, which supports the claim that attention resource was limited, and we further proposed that AVI was positively modulated by attentional resource. Finally, there were substantial impacts of aging on AVI; AVI was delayed in older adults., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an infinite cell source for cardiovascular disease modeling, drug screening and cell therapy. Despite extensive efforts, current approaches have failed to generate hPSC-CMs with fully adult-like phenotypes in vitro , and the immature properties of hPSC-CMs in structure, metabolism and electrophysiology have long been impeding their basic and clinical applications. The prenatal-to-postnatal transition, accompanied by severe nutrient starvation and autophagosome formation in the heart, is believed to be a critical window for cardiomyocyte maturation. In this study, we developed a new strategy, mimicking the in vivo starvation event by Earle's balanced salt solution (EBSS) treatment, to promote hPSC-CM maturation in vitro . We found that EBSS-induced starvation obviously activated autophagy and mitophagy in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Intermittent starvation, via 2-h EBSS treatment per day for 10 days, significantly promoted the structural, metabolic and electrophysiological maturation of hESC-CMs. Structurally, the EBSS-treated hESC-CMs showed a larger cell size, more organized contractile cytoskeleton, higher ratio of multinucleation, and significantly increased expression of structure makers of cardiomyocytes. Metabolically, EBSS-induced starvation increased the mitochondrial content in hESC-CMs and promoted their capability of oxidative phosphorylation. Functionally, EBSS-induced starvation strengthened electrophysiological maturation, as indicated by the increased action potential duration at 90% and 50% repolarization and the calcium handling capacity. In conclusion, our data indicate that EBSS intermittent starvation is a simple and efficient approach to promote hESC-CM maturation in structure, metabolism and electrophysiology at an affordable time and cost., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Ding, Zhao, Yu, Shao, Ni, Zhao, Li, Chen, Ying, Yu, Lei and Hu.)