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Abstract Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.

Rainfall data with high spatial and temporal resolutions are essential for urban hydrological modeling. Ubiquitous surveillance cameras can continuously record rainfall events through video and audio, so they have been recognized as potential rain gauges to supplement professional rainfall observation networks. Since video-based rainfall estimation methods can be affected by variable backgrounds and lighting conditions, audio-based approaches could be a supplement without suffering from these conditions. However, most audio-based approaches focus on rainfall-level classification rather than rainfall intensity estimation. Here, we introduce a dataset named Surveillance Audio Rainfall Intensity Dataset (SARID) and a deep learning model for estimating rainfall intensity. First, we created the dataset through audio of six real-world rainfall events. This dataset's audio recordings are segmented into 12,066 pieces and annotated with rainfall intensity and environmental information, such as underlying surfaces, temperature, humidity, and wind. Then, we developed a deep learning-based baseline using Mel-Frequency Cepstral Coefficients (MFCC) and Transformer architecture to estimate rainfall intensity from surveillance audio. Validated from ground truth data, our baseline achieves a root mean absolute error of 0.88 mm h-1 and a coefficient of correlation of 0.765. Our findings demonstrate the potential of surveillance audio-based models as practical and effective tools for rainfall observation systems, initiating a new chapter in rainfall intensity estimation. It offers a novel data source for high-resolution hydrological sensing and contributes to the broader landscape of urban sensing, emergency response, and resilience.

Highlights A comprehensive introduction into organic cathode materials for aqueous zinc-ion batteries with specific focus on their structural–property relationship based on the variations in composition, geometry, and molecular size. For each representative organic cathode, the unique electrochemistry has been discussed to provide insight into the underlying working mechanism. Summarized pros and cons of different organic cathodes and outlined challenges plus future research directions.

Abstract Rationally designed organic redox‐active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor–Acceptor (D–A) bipolar polymer with n‐type pyrene‐4,5,9,10‐tetraone unit storing Li cations and p‐type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium‐ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D–A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g−1 at 200 mA g−1, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g−1 at 10 A g−1 and a noteworthy energy density up to 554 Wh kg−1. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.

Forests emit a large amount of biogenic volatile organic compounds (BVOCs) in response to biotic and abiotic stress. Despite frequent occurrence of large forest fires in recent years, the impact of smoke stress derived from these forest fires on the emission of BVOCs is largely unexplored. Thus, the aims of the study were to quantify the amount and composition of BVOCs released by two sub-tropical tree species, Cunninghamia lanceolata and Schima superba, in response to exposure to smoke. Physiological responses and their relationship with BVOCs were also investigated. The results showed that smoke treatments significantly (p < 0.001) promoted short-term release of BVOCs by C. lanceolata leaves than S. superba; and alkanes, olefins and benzene homologs were identified as major classes of BVOCs. Both C. lanceolata and S. superba seedlings showed significant (p < 0.005) physiological responses after being smoke-stressed where photosynthetic rate remained unaffected, chlorophyll content greatly reduced and Activities of anti-oxidant enzymes and the malondialdehyde content generally increased with the increase in smoke concentration. Activities of anti-oxidant enzymes showed mainly positive correlations with the major BVOCs. In conclusion, the release of BVOCs following smoke stress is species-specific and there exists a link between activities of antioxidant enzymes and BVOCs released. The findings provide insight about management of forest fires in order to control excessive emission of smoke that would trigger increased release of BVOCs.

Time course analysis of eye movements during free exploration of real-world scenes often reveals an increase in fixation durations together with a decrease in saccade amplitudes, which has been explained within the two visual systems approach, i.e., a transition from ambient to focal. Short fixations and long saccades during early viewing periods are classified as ambient mode of vision, which is concerned with spatial orientation and is related to simple visual properties such as motion, contrast, and location. Longer fixations and shorter saccades during later viewing periods are classified as focal mode of vision, which is concentrated in the foveal projection and is capable of object identification and its semantic categorization. While these findings are mainly obtained in the context of image exploration, the present study endeavors to investigate whether the same pattern of interplay between ambient and focal visual attention is deployed when people work on complex real-world tasks—and if so, when? Based on a re-analysis of existing data that integrates concurrent think aloud and eye tracking protocols, the present study correlated participants’ internal thinking models to the parameters of their eye movements when they planned solutions to an open-ended design problem in a real-world setting. We hypothesize that switching between ambient and focal attentional processing is useful when solvers encounter difficulty compelling them to shift their conceptual direction to adjust the solution path. Individuals may prefer different attentional strategies for information-seeking behavior, such as ambient-to-focal or focal-to-ambient. The observed increase in fixation durations and decrease in saccade amplitudes during the periods around shifts in conceptual direction lends support to the postulation of the ambient-to-focal processing; however, focal-to-ambient processing is not evident. Furthermore, our data demonstrate that the beginning of a shift in conceptual direction is observable in eye movement behavior with a significant prolongation of fixation. Our findings add to the conclusions drawn from laboratory settings by providing preliminary evidence for ambient and focal processing characteristics in real-world problem-solving.

During satellite remote sensing imaging, the use of Bayer mode sensors holds significant importance in saving airborne computing resources and reducing the burden of satellite transmission systems. The demosaicing techniques play a key role in this process. The integration of Generative Adversarial Networks (GANs) has garnered significant interest in the realm of image demosaicking, owing to their ability to generate intricate details. However, when demosaicing mosaic images in remote sensing techniques, GANs, although capable of generating rich details, often introduce unpleasant artifacts while generating content. To address this challenge and differentiate between undesirable artifacts and realistic details, we have devised a novel framework based on a Progressive Discrimination Strategy within a Generative Adversarial Network architecture for image demosaicking. Our approach incorporates an artifact-weighted Location Map refinement technique to guide the optimization process towards generating authentic details in a stable and precise manner. Furthermore, our framework integrates a global attention mechanism to boost the interaction of spatial-channel information across different dimensions, thereby enhancing the performance of the generator network. Moreover, we conduct a comparative analysis of various prevalent attention mechanisms in the context of remote sensing image demosaicking. The experimental findings unequivocally demonstrate that our proposed methodology not only achieves superior reconstruction accuracy on the dataset but also enhances the perceptual quality of the generated images. By effectively mitigating artifacts and emphasizing the generation of true details, our approach represents a significant advancement in the field of remote sensing image demosaicking, promising enhanced visual fidelity and realism in reconstructed images.

Sorafenib, a multi-targeted tyrosine kinase inhibitor, is a first-line treatment for advanced solid tumors, but it induces many adverse cardiovascular events, including myocardial infarction and heart failure. These cardiac defects can be mediated by alternative splicing of genes critical for heart function. Whether alternative splicing plays a role in sorafenib-induced cardiotoxicity remains unclear. Transcriptome of rat hearts or human cardiomyocytes treated with sorafenib was analyzed and validated to define alternatively spliced genes and their impact on cardiotoxicity. In rats, sorafenib caused severe cardiotoxicity with decreased left ventricular systolic pressure, elongated sarcomere, enlarged mitochondria and decreased ATP. This was associated with alternative splicing of hundreds of genes in the hearts, many of which were targets of a cardiac specific splicing factor, RBM20. Sorafenib inhibited RBM20 expression in both rat hearts and human cardiomyocytes. The splicing of RBM20’s targets, SLC25A3 and FHOD3, was altered into fetal isoforms with decreased function. Upregulation of RBM20 during sorafenib treatment reversed the pathogenic splicing of SLC25A3 and FHOD3, and enhanced the phosphate transport into mitochondria by SLC25A3, ATP synthesis and cell survival.We envision this regulation may happen in many drug-induced cardiotoxicity, and represent a potential druggable pathway for mitigating sorafenib-induced cardiotoxicity.

Abstract Conventional robotic systems are built with rigid materials to deal with large forces and predetermined processes. Soft robotics, however, is an emerging field seeking to develop adaptable robots that can perform tasks in unpredictable environments and biocompatible devices that close the gap between humans and machines. Dielectric elastomers (DEs) have emerged as a soft actuation technology that imitates the properties and performance of natural muscles, making them an attractive material choice for soft robotics. However, conventional DE materials suffer from electromechanical instability (EMI), which reduces their performance and limits their applications in soft robotics. This review discusses key innovations in DE artificial muscles from a material standpoint, followed by a survey on their representative demonstrations of soft robotics. Specifically, we introduce modifications of DE materials that enable large strains, fast responses, and high energy densities by suppressing EMI. Additionally, we examine materials that allow variable stiffness and self‐healing abilities in DE actuators. Finally, we review dielectric elastomer actuator (DEA) applications in soft robotics in four categories, including automation, manipulation, locomotion, and human interaction.

The p97 unfoldase is an essential and abundant enzyme that segregates its substrates from macromolecular complexes and organelle membranes. Here, authors determined the structure of human p97 in the act of unfolding an authentic substrate.

Heart muscle cells exhibit exquisitely organized subcellular features that enable efficient and coordinated heart muscle contraction, but little is known about how it is achieved. Here the authors show that CMYA5 organizes cardiomyocyte calcium release units and aligns them to sarcomeres, leading to abnormal calcium release, cardiac dysfunction, and inability to tolerate pressure overload, when absent.

Gene editing stands for the methods to precisely make changes to a specific nucleic acid sequence. With the recent development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, gene editing has become efficient, convenient and programmable, leading to promising translational studies and clinical trials for both genetic and non-genetic diseases. A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome. To date, many methods have been developed to nominate or detect the off-target sites of CRISPR/Cas9, which laid the basis for the successful upgrades of CRISPR/Cas9 derivatives with enhanced precision. In this review, we summarize these technological advancements and discuss about the current challenges in the management of off-target effects for future gene therapy.

Reactive oxygen species (ROS) affect meat quality through multiple biochemical pathways. To investigate the effect of ROS on postmortem glycolysis and tenderness of bovine muscle, ROS content, glycolytic potential, glycolysis rate-limiting enzyme activities, expression of hypoxia-inducible factor-1α (HIF-1α), phosphatidylinositol 3-kinase (PI3K), serine-threonine kinase (AKT), phosphorylated AKT (p-AKT), and tenderness were determined in the H2O2 group and control group. Results showed that the H2O2 group exhibited significantly higher ROS content within 48 h, coupled with increased glycolytic potential, pH decline, hexokinase (HK), and phosphofructokinase activities (PFK) early postmortem. These were attributed to ROS-induced PI3K/AKT signaling pathway activation and resultant HIF-1α accumulation. Moreover, shear force in the H2O2 group reached the peak 12 h earlier and decreased obviously after 24 h, accompanied by a significantly higher myofibril fragmentation index (MFI). These findings suggested that ROS drive HIF-1α accumulation by activating PI3K/AKT signaling pathway, thereby accelerating glycolysis and tenderization of postmortem bovine muscle.

Throughput of in vivo genetic screens is a barrier to efficient application. Here the authors use a high-throughput CRISPR-based in vivo forward genetic screen in mice to identify transcriptional regulators of cardiomyocyte maturation, including the epigenetic modifiers RNF20 and RNF40.

Background: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the ACTN2 and RYR2 genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the ACTN2 and RYR2 genes. Case Presentation: The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the ACTN2 g.236,686,454-236,764,631_del and RYR2 g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the ACTN2 and RYR2 genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy.

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) is a key player in cardiomyocyte calcium handling and also a classic target in the gene therapy for heart failure. SERCA2 expression dramatically increases during cardiomyocyte maturation in the postnatal phase of heart development, which is essential for the heart to acquire its full function in adults. However, whether and how SERCA2 regulates cardiomyocyte maturation remains unclear. Here, we performed Cas9/AAV9-mediated somatic mutagenesis (CASAAV) in mice and achieved cardiomyocyte-specific knockout of Atp2a2, the gene coding SERCA2. Through a cardiac genetic mosaic analysis, we demonstrated the cell-autonomous role of SERCA2 in building key ultrastructures of mature ventricular cardiomyocytes, including transverse-tubules and sarcomeres. SERCA2 also exerts a profound impact on oxidative respiration gene expression and sarcomere isoform switching from Myh7/Tnni1 to Myh6/Tnni3, which are transcriptional hallmarks of cardiomyocyte maturation. Together, this study uncovered a pivotal role of SERCA2 in heart development and provided new insights about SERCA2-based cardiac gene therapy.

Among the patterning technologies for organic thin-film transistors (OTFTs), the fabrication of OTFT electrodes using polymer templates has attracted much attention. However, deviations in the electrode alignment occur because the coefficient of thermal expansion (CTE) of the polymer template is much higher than the CTE of the dielectric layer. Here, a novel dry-blending method is described in which SiO2 nanoparticles are filled into a grooved silicon template, followed by permeation of polydimethylsiloxane (PDMS) into the SiO2 nanoparticle gaps. The SiO2 nanoparticles in the groove are extracted by curing and peeling off PDMS to prepare a PDMS/SiO2 composite template with a nanoparticle content of 83.8 wt %. The composite template has a CTE of 96 ppm/°C, which is a reduction by 69.23% compared with the original PDMS template. Finally, we achieved the alignment of OTFT electrodes using the composite template.

In this paper, we propose a reptile search algorithm based on Lévy flight and interactive crossover strategy (LICRSA), and the improved algorithm is employed to improve the problems of poor convergence accuracy and slow iteration speed of the reptile search algorithm. First, the proposed algorithm increases the variety and flexibility of the people by introducing the Lévy flight strategy to prevent premature convergence and improve the robustness of the population. Secondly, an iteration-based interactive crossover strategy is proposed, inspired by the crossover operator and the difference operator. This strategy is applied to the reptile search algorithm (RSA), and the convergence accuracy of the algorithm is significantly improved. Finally, the improved algorithm is extensively tested using 2 test sets: 23 benchmark test functions and 10 CEC2020 functions, and 5 complex mechanical engineering optimization problems. The numerical results show that LICRSA outperforms RSA in 15 (65%) and 10 (100%) of the 2 test sets, respectively. In addition, LICRSA performs best in 10 (43%) and 4 (40%) among all algorithms. Meanwhile, the enhanced algorithm shows superiority and stability in handling engineering optimization.

The processes regulating cardiomyocyte (CM) maturation are unclear. Here, the authors show that serum response factor regulates CM maturation only in neonatal CMs through stage-specific chromatin occupancy that affects cell size, sarcomere and transverse-tubule organization, and mitochondria

Superhydrophilic glass has aroused significant interest and attention among researchers because of their excellent performance. A variety of methods by modifying features of the glass such as surface roughness, surface energy, surface chemistry, or charge distribution. Unlike the electro-wetting phenomenon via electric-field-driven accumulation of solid–liquid interfacial charges, we report charge injection-induced accumulation phenomena on the solid surface. The wettability of a glass slide changed from hydrophilic to superhydrophilic by charge injection and heating, and the hydrophilic was restored by heating, which yields a reversible hydrophilic–superhydrophilic conversion. The influences of voltage, temperature, and charging time on the coating wettability, and its durability under reversible conversion have been determined.

In order to solve the problem of gas overlimit in corner corners of coal and gas prominent mines, through the combination of air leakage mechanism in the goaf, near-field fissure expansion and rich area division, blocking material development and optimization, performance measurement of blocking materials and on-site test, we started to study the causes of gas concentration in corner corners, analysis of roof collapse and transparency in corners and performance test of blocking materials, and optimized the blocking materials by combining laboratory test and engineering test. Considering the thickness of the sealing film, the attenuation ratio of the sealing film thickness, the gelation time, and the gelation viscosity under different ratios, we designed a multi factor orthogonal experiment to optimize the optimal ratio suitable for the engineering site. Factors affecting blocking effectiveness, such as gel water retention and gel flame resistance, were also tested. The sealing scheme was implemented in the 2109 working face of a coal and gas outburst mine in Gansu, China. Through on-site monitoring of the changes in temperature, gas concentration, and air leakage at each monitoring point before and after the use of sealing materials, the analysis of the detection results shows that the temperature changes at each monitoring point after the use of sealing materials do not exceed 0.2°C; The change in oxygen concentration is less than 0.27 %; The gas concentration has decreased by more than 60 %, with a decrease of 71.32 % in the gas concentration in the upper corner. The air leakage has decreased by more than 53 %, and the proportion of decrease in air leakage at the upper corner is as high as 56.83 %. This air leakage control technology has remarkable blocking effect, meets the requirements of corner near-field fissure blocking material, and is easy to prepare, inexpensive, non-toxic, tasteless and green, providing a successful experience for the treatment of similar coal and gas outburst mines that can be referenced. [ABSTRACT FROM AUTHOR]