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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]

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]

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]

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]