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To study the effects of radio frequency-assisted hot air drying (RFHAD) on the quality of South American white shrimp (Penaeus vannamei), the RFHAD process based on the dielectric properties of the shrimp was optimized. The effects of radio frequency drying (RFD) and RFHAD on the flavor nucleotide contents and equivalent umami levels in dried shrimp were compared with those of hot-air drying (HAD). The results showed that as the temperature and moisture content increased, the dielectric constant and loss factor of the shrimp also increased, facilitating moisture migration and enhancing the drying rate. The penetration depth of the RFD was negatively correlated with moisture content, temperature, and frequency. Additionally, increasing the number of stacked layers and reducing the plate spacing significantly increased the drying rate of the shrimp (P

In order to realize the effective prevention and control of coal dust, the magnetic-electric coupling spray dust reduction technology is proposed. First, by measuring the surface tension and contact angle of magnetized water under different magnetization intensities and magnetization times, its wetting and atomization properties are analyzed. Secondly, the magnetized water was magnetized with optimal parameters to increase the applied electric field to explore the effects of electrode voltage, electrode ring parameters, and electrode spacing on the charging characteristics and atomization performance of magneto-electrically coupled water. Then, the dust reduction effects of ordinary water, magnetized water and magneto-electrically coupled water were compared by the self-built dust removal experimental platform. Finally, COMSOL software is used to simulate the changes of collision patterns between the above three liquids and coal dust particles. The experimental results show that: the best dust reduction parameters of magnetized water solution are magnetization intensity of 350 mT and magnetization time of 30 min; the best parameters of magneto-electrically coupled water are electrode voltage of 9 kV, electrode ring parameter of 8 cm and electrode spacing of 3.5 cm; the dust reduction efficiency of magneto-electrically coupled solution is higher than that of other two kinds of liquids, and the dust capturing efficiency of magneto-electrically coupled spray is increased by 38.84% compared with that of ordinary water at the time of total dust, and the dust reduction efficiency reaches 91.2%; the dust capture efficiency of the magneto-electrically coupled spray is 38.59% higher than that of ordinary water in respirable dust, and the dust reduction efficiency reaches 82.3%. The droplets are more easily adhered to the surface of coal dust particles under the three working conditions of ordinary water, magnetized water and magneto-electrically coupled solution.

Abstract This study was performed to investigate the diagnostic value of radiomics models constructed by fat suppressed T2-weighted imaging (T2WI-FS) and contrast-enhanced T1-weighted imaging (CET1) based on magnetic resonance imaging (MRI) for differentiation of osteosarcoma (OS) and chondrosarcoma (CS). In this retrospective cohort study, we included all inpatients with pathologically confirmed OS or CS from Second Xiangya Hospital of Central South University (Hunan, China) as of October 2020. Demographic and imaging variables were extracted from electronic medical records and compared between OS and CS group. Totals of 530 radiomics features were extracted from CET1 and T2WI-FS sequences based on MRI. The least absolute shrinkage and selection operator (LASSO) method was used for screening and dimensionality reduction of the radiomics model. Multivariate logistic regression analysis was performed to construct the radiomics model, and receiver operating characteristic curve (ROC) was generated to evaluate the diagnostic accuracy of the radiomics model. The training cohort and validation cohort included 87 and 29 patients, respectively. 8 CET1 features and 15 T2WI-FS features were screened based on the radiomics features. In the training group, the area under the receiver-operator characteristic curve (AUC) value for CET1 and T2WI-FS sequences in the radiomics model was 0.894 (95% CI 0.817–0.970) and 0.970 (95% CI 0.940–0.999), respectively. In the validation group, the AUC value for CET1 and T2WI-FS sequences in the radiomics model was 0.821 (95% CI 0.642–1.000) and 0.899 (95% CI 0.785–1.000), respectively. In this study, we developed a radiomics model based on T2WI-FS and CET1 sequences to differentiate between OS and CS. This model exhibits good performance and can help clinicians make decisions and optimize the use of healthcare resources.

The genus Hydrurus contains a solitary species, Hydrurus foetidus. Its thalli exhibit a remarkable structure, consisting of a firm central axis surrounded by peripheral branches, all enveloped within a viscous, gelatinous coating. Molecular data pertaining to the genus Hydrurus are scarce, necessitating further investigation into its phylogenetic relationships.A new site with benthic freshwater alga Hydrurus foetidus (Villars) Trevisan has been discovered in the Fenhe River in Shanxi Province, China. The physical and chemical parameters of water were meticulously measured and documented. Detailed morphological observations were conducted on the specimen, measuring different cell categories. The SSU, LSU, ITS and rbcL DNA sequence data of H. foetidus collected from Shanxi were determined. An extensive three-gene phylogenetic tree was constructed, revealing a strong relationship between the specimen in this study and H. foetidus specimen from Norway. Time-calibrated molecular phylogenetic analysis further indicated that the genus Hydrurus diverged approximately 125 million years ago (Early Cretaceous), while the two H. foetidus strains from Shanxi, China and Norway diverged approximately 6 million years ago (Neogene). The results of this study supplement new molecular evidence for H. foetidus and contribute significantly to our understanding of the geographical distribution and evolutionary history of the genus Hydrurus.

In response to the rapid growth of future business and data traffic, the widespread deployment of small base stations (BSs) in 5G networks has emerged as a promising solution, albeit intensifying the network’s energy consumption. Additionally, traditional BSs lack adaptive adjustment of parameter information, posing challenges in delivering satisfactory quality of service (QoS), particularly in the context of highly uneven business distribution. Reducing energy consumption while ensuring that QoS represents a critical challenge. To address this issue, this paper first comprehensively considers the interests of both supply and demand, proposing a service utility measurement method in communication networks to achieve a balance between energy consumption and QoS. Furthermore, this paper integrates cell zooming and sleeping strategies for small BSs, designing a dynamic game algorithm aimed at optimizing service utility in a two-tier heterogeneous network. Through ten distinct scenario simulations, our proposed algorithm demonstrates significant enhancements in service utility while achieving near-optimal optimization results more expeditiously compared to the genetic algorithm (GA).

The dense deployment of Femto Base Stations (FBS) assisting Macro Base Stations (MBS) in a Heterogeneous Network (HetNet) resolves the coverage issue of 5G signal transmission. However, the imprudent layout of FBSs results in extensive energy consumption and increased signal interference among base stations. Regulating the transmission power of each base station in the HetNets through the main controller or MBS is essential to maximize the power efficiency of the entire HetNets while adhering to the constraints of basic signal throughput and fairness. To address this challenge, this paper proposes an Adaptive Acceleration Particle Swarm Optimization (AA-PSO) algorithm. This algorithm dynamically determines the inertia weight based on each particle’s optimal position and the global optimal position, and introduces the concept of time-varying parameters to control the learning rate, thus managing the search range and convergence speed of the particle swarm. The results demonstrate that the AA-PSO algorithm can efficiently determine the optimal transmission power of each base station in the HetNets, reduce interference between MBS and FBSs, as well as among FBSs, and ultimately improve the service efficacy of the entire network.

Abstract Background Algae play important roles in urban river ecosystems and are the cornerstones of most water quality monitoring programs. Thus, a better understanding of algal community dynamics is needed to support sustainable management of water resources in urban rivers. Results In this study, we quantified the seasonal variations in planktonic and periphytic algal community structure in the highly urban Fenhe River and identified environmental factors affecting algal community structure and diversity. We monitored planktonic (drifting) and periphytic (attached) algal communities in the Taiyuan section of the Fenhe River over one year. The results indicated that Cyanophyta was the dominant phylum in both communities, followed by Bacillariophyta and Chlorophyta. Significant differences were observed in the composition of the planktonic and periphytic algal communities. In particular, the periphytic algal community was more diverse than the planktonic community. Water temperature and pH were the main environmental factors affecting planktonic and periphytic algal community structure, respectively, while nutrients were the most significant factor affecting planktonic and periphytic algal diversity. Ecological modeling indicated that the variations in the algal communities of the Fenhe River are mainly driven by stochastic processes. A co-occurrence network developed for the communities displayed positive interactions between the planktonic and periphytic algae. Conclusions These findings deepen our understanding of the seasonal interaction between planktonic and periphytic algae and the driving factors affecting community structure in the Fenhe River. They also provide a theoretical basis for the managing and protecting water resources in urban river ecosystems.

Abstract Tumor ecosystem shapes cancer biology and potentially influence the response to immunotherapy, but there is a lack of direct clinical evidence. In this study, we utilized EcoTyper and publicly available scRNA-Seq cohorts from ICI-treated patients. We found a ecosystem subtype (ecotype) was linked to improved responses to immunotherapy. Then, a novel immunotherapy-responsive ecotype signature (IRE.Sig) was established and validated through the analysis of pan-cancer data. Utilizing IRE.Sig, machine learning models successfully predicted ICI responses in both validation and testing cohorts, achieving area under the curve (AUC) values of 0.72 and 0.71, respectively. Furthermore, using 5 CRISPR screening cohorts, we identified several potential drugs that may augment the efficacy of ICI. We also elucidated the candidate cellular biomarkers of response to the combined treatment of pembrolizumab plus eribulin in breast cancer. This signature has the potential to serve as a valuable tool for patients in selecting appropriate immunotherapy treatments.

The research team has developed an information system based on clinical blood cell analysis and designed and implemented highly innovative algorithms. A neural network model was created based on these feature data of the blood cell population. Artificial intelligence algorithms can label susceptible populations for digestive tract cancer with an accuracy rate of over 80 %. A multi universe optimized BP neural network model was implemented based on TCGA data of common immune antigens in clinical laboratories. The working mechanism of this model is to assign values to the parameters of the BP neural network by using the process of searching for the best fitness in multiple universes. This model can predict the five-year survival rate of patients based on immunohistochemical data. Based on these data, an AI algorithm was used to develop a clinical prognostic model with an accuracy rate of over 99 %. The research team used single-cell sequencing data to locate cell subtypes in the features of immunohistochemical data, providing a biological basis for artificial intelligence models. The research team explored the potential biological mechanisms of cancer progression and occurrence based on gastrointestinal neuroendocrine products, and these algorithms have contributed to the prediction of cancer survival and incidence,team invented a simple and efficient algorithm.

The thermostable α-amylase derived from Bacillus licheniformis (BLA) has multiple advantages, including enhancing the mass transfer rate and by reducing microbial contamination in starch hydrolysis. Nonetheless, the application of BLA is constrained by the accessibility and stability of enzymes capable of achieving high conversion rates at elevated temperatures. Moreover, the thermotolerance of BLA requires further enhancement. Here, we developed a computational strategy for constructing small and smart mutant libraries to identify variants with enhanced thermostability. Initially, molecular dynamics (MD) simulations were employed to identify the regions with high flexibility. Subsequently, FoldX, a computational design predictor, was used to design mutants by rigidifying highly flexible residues, whereas the simultaneous decrease in folding free energy assisted in improving thermostability. Through the utilization of MD and FoldX, residues K251, T277, N278, K319, and E336, situated at a distance of 5 Å from the catalytic triad, were chosen for mutation. Seventeen mutants were identified and characterized by evaluating enzymatic characteristics and kinetic parameters. The catalytic efficiency of the E271L/N278K mutant reached 184.1 g L−1 s−1, which is 1.88-fold larger than the corresponding value determined for the WT. Furthermore, the most thermostable mutant, E336S, exhibited a 1.43-fold improvement in half-life at 95 ℃, compared with that of the WT. This study, by combining computational simulation with experimental verification, establishes that potential sites can be computationally predicted to increase the activity and stability of BLA and thus provide a possible strategy by which to guide protein design.

Abstract Background The administration of tranexamic acid (TXA) during spinal surgery has been shown to reduce blood loss. However, the efficacy and safety of intravenous TXA (ivTXA) and topical TXA (tTXA) are poorly documented. The present meta-analysis aimed to compare the efficacy and safety of ivTXA and tTXA administration in spinal surgery. Methods Potentially relevant academic articles were identified from PubMed, Ovid, Cochrane Library, CNKI database, and Wanfang Data from the date of inception until March 1, 2024. Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) were included in our meta-analysis if they compared the efficacy and safety of ivTXA versus tTXA administration during spinal surgery. Secondary sources were identified from the references of the included literature. The meta-analysis was performed in accordance with the guidelines of the Cochrane Reviewer’s Handbook and the PRISMA statement. Data were summarized using RevMan 5.3 software from Denmark. Results Four RCTs and one non-RCT met our inclusion criteria. The pooled outcomes demonstrated that ivTXA groups compared with tTXA groups had significantly less amount of total blood loss [weighted mean difference (WMD)=-159.55, 95% CI (-181.91,-137.19), P

Abstract The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy. Graphical Abstract

Abstract Background The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It’s unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. Methods This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. Results In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018–2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020–2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. Conclusion Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

Abstract The inadequate stability of organic–inorganic hybrid perovskites remains a significant barrier to their widespread commercial application in optoelectronic devices. Aging phenomena profoundly affect the optoelectronic performance of perovskite-based devices. In addition to enhancing perovskite stability, the real-time detection of aging status, aimed at monitoring the aging progression, holds paramount importance for both fundamental research and the commercialization of organic–inorganic hybrid perovskites. In this study, the aging status of perovskite was real-time investigated by using terahertz time-domain spectroscopy. Our analysis consistently revealed a gradual decline in the intensity of the absorption peak at 0.968 THz with increasing perovskite aging. Furthermore, a systematic discussion was conducted on the variations in intensity and position of the terahertz absorption peaks as the perovskite aged. These findings facilitate the real-time assessment of perovskite aging, providing a promising method to expedite the commercialization of perovskite-based optoelectronic devices. Graphical Abstract

Abstract Background The objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC). Methods Utilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission. Results During the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60–0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34–0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33–0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15–0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P

Al–Zn–Mg–Cu alloys have remarkable plasticity and aging-hardening potential, while natural aging during storage and transportation dramatically increases the strength of the alloys and deteriorates the formability by generating massive high-density nano-scaled -clusters. In this study, a combination of pre-aging and regression heat treatment was employed to improve the negative effects of natural aging via regulating the distribution of precipitates and reducing the dissolving ratio. Atomic probe tomography and transmission electron microscope observations were mainly carried out to reveal the mechanism of microstructure evolution caused by heat treatments. The results reveal that the distributions of precipitate density and size vary with different pre-aging time, resulting in the differences in dissolving critical sizes and dissolving ratios of precipitates during regression heat treatments. For the limited pre-aging time, the dramatic dissolution of nano-scale clusters caused the surge of solute concentration in the matrix after regression heat treatments, resulting in considerable secondary precipitation of clusters during the subsequent natural aging process. With the increase of pre-aging time, the size and density of precipitates gradually increased, which reduced the dissolving ratio of precipitates during regression heat treatments. However, as the dissolving ratio declined from around 97.5 % (pre-aging for 0 h) to approx. 69.2 % (pre-aging for 18 h), the solute concentration in the matrix was lower than the secondary precipitation level of clusters, thus suppressing natural aging. Overall, this work provides a novel strategy to control the nature-aging behavior of Al–Zn–Mg–Cu alloys. Meanwhile, the correlation between microstructure evolution and mechanical properties under different heat treatments was systematically discussed.

Abstract Thermally stable full-length scorpion toxin peptides and partially degraded peptides with complete disulfide bond pairing are valuable natural peptide resources in traditional Chinese scorpion medicinal material. However, their pharmacological activities are largely unknown. This study discovered BmKcug1a-P1, a novel N-terminal degraded peptide, in this medicinal material. BmKcug1a-P1 inhibited hKv1.2 and hKv1.3 potassium channels with IC50 values of 2.12 ± 0.27 μM and 1.54 ± 0.28 μM, respectively. To investigate the influence of N-terminal amino acid loss on the potassium channel inhibiting activities, three analogs (i.e., full-length BmKcug1a, BmKcug1a-P1-D2 and BmKcug1a-P1-D4) of BmKcug1a-P1 were prepared, and their potassium channel inhibiting activities on hKv1.3 channel were verified by whole-cell patch clamp technique. Interestingly, the potassium channel inhibiting activity of full-length BmKcug1a on the hKv1.3 channel was significantly improved compared to its N-terminal degraded form (BmKcug1a-P1), while the activities of two truncated analogs (i.e., BmKcug1a-P1-D2 and BmKcug1a-P1-D4) were similar to that of BmKcug1a-P1. Extensive alanine-scanning experiments identified the bonding interface (including two key functional residues, Asn30 and Arg34) of BmKcug1a-P1. Structural and functional dissection further elucidated whether N-terminal residues of the peptide are located at the bonding interface is important in determining whether the N-terminus significantly influences the potassium channel inhibiting activity of the peptide. Altogether, this research identified a novel N-terminal degraded active peptide, BmKcug1a-P1, from traditional Chinese scorpion medicinal material and elucidated how the N-terminus of peptides influences their potassium channel inhibiting activity, contributing to the functional identification and molecular truncation optimization of full-length and degraded peptides from traditional Chinese scorpion medicinal material Buthus martensii Karsch.

Abstract Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, bla CTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.

Abstract In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin–eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia–reperfusion injury.

Abstract Nucleotides, such as uridine 5′‐monophosphate (5′‐UMP) and cytidine 5′‐monophosphate (5′‐CMP), are heavily demanded as food additives, dietary supplements, and medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application is challenging due to the need for the expensive enzymes and coenzyme guanosine‐5′‐triphosphate (GTP). Here we prepared biocompatible calcium‐based nanoflowers incorporated with cascade enzymes, uridine‐cytidine kinase (UCK) and acetate kinase (ACK), for the production of nucleotides. The spatial distribution of these enzymes was optimized to maximize their catalytic performances. The most active nanoflowers (Ca3(PO4)2& ACK)& UCK that display the rate‐limiting enzyme UCK on the outer layer were used in a packed‐bed reactor for continuous synthesis of 5′‐UMP and 5′‐CMP. The catalytic performance of the catalyst retained over 80% within 10 h, showing good operational stability.

Abstract Objective This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. Methods The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain’s sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. Results Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. Conclusion This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as bla NDM−1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.

Abstract. The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies. However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product. Moreover, they can kill cancer cells via CAR-dependent/independent pathways and have limited toxicity. Macrophages are the most malleable immune cells in the body. These cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments (TMEs). Importantly, CAR-macrophages (CAR-Ms) have recently yielded exciting preclinical results in several solid tumors. Nevertheless, CAR-T, CAR-NK, and CAR-M all have their own advantages and limitations. In this review, we systematically discuss the current status, progress, and the major hurdles of CAR-T cells, CAR-NK cells, and CAR-M as they relate to five aspects: CAR structure, therapeutic mechanisms, the latest research progress, current challenges and solutions, and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.

Abstract It is essential to elucidate the mechanical mechanism of water injection and large-diameter drilling pressure relief measures on coal rock deformation and failure. This helps coal mines adopt more precise and effective dynamic disaster prevention and control measures. To obtain the mechanical response mechanism and energy evolution characteristics of saturated coal with a single pre-existing hole, uniaxial compression tests was carried out, and the deformation and failure process of coal samples were monitored by high-speed camera and acoustic emission monitoring systems. It is found that water saturation, single pre-existing hole measures, and their coupling effect resulted in a deterioration in the coal sample's strength by approximately 23.49%, 9.47%, and 47.95% respectively. The final failure mode of coal samples with different measures is shear failure. The law of fracture development and expansion and energy accumulation and release in different coal samples is roughly the same, the speed of energy accumulation and release in different stages is different. Water saturation and single pre-existing hole measures can affect the impact risk of coal samples, and water saturation can significantly reduce the impact tendency of coal samples, and reduce the impact energy index of complete coal samples by 56.59%. The impact tendency index of natural coal sample is slightly increased by single pre-existing hole measure, and the impact energy index of intact coal sample is reduced by 46.78% by the coupling of the two measures. These findings can provide technical support for coal mine power disaster prevention and control.

Interleukin-15 (IL-15) is a crucial cytokine involved in immune system regulation, which is produced by various cell types, including dendritic cells, monocytes, and macrophages. IL-15 plays a key role in the proliferation and activation of natural killer (NK) cells, CD8+ T cells, and memory CD8+ T cells, supporting their survival and enhancing their effector functions. Although IL-15 homologues in fish have been identified, their functions remain poorly understood. In this study, we cloned and investigated the bioactivities of an IL-15 homologue, referred to as IL-15 like (CcIL-15L), in common carp (Cyprinus carpio L.). An expression pattern analysis revealed that CcIL-15L was constitutively expressed in all examined tissues of healthy common carp, with the highest expression level observed in the intestine. Additionally, CcIL-15L expression was significantly up-regulated in the head kidney, spleen, gills, and intestine following Aeromonas hydrophila infection. In vitro, the recombinant protein CcIL-15L can significantly up-regulated the gene expression levels of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF-α) and NK cell activation (perforin and Eomesa). We constructed a 3×FLAG eukaryotic expression vector and successfully expressed it in common carp by intramuscular injection. Additionally, the heterologous CcIL-15L protein was successfully overexpressed in vivo, and immune-related genes including CD4-1, CD8β2, TNF-α, and IgM showed significant induction in the head kidney and spleen. Furthermore, CcIL-15L overexpression reduced the bacterial loads after 24 h post-A. hydrophila infection in the liver, spleen, and kidney. Phagocytic and chemotaxis assays showed that rCcIL-15L could promoted the phagocytosis and chemotactic abilities of common carp HKLs. Our study provides a new perspective on the role for CcIL-15L in immunological functions in common carp.

Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

Objective To analyze the geographic variation in characteristics and treatment processes of patients with acute ischemic stroke (AIS) in coastal, island, and inland regions. Methods We conducted a retrospective, cross-sectional analysis of data from patients with AIS in southeastern China. We collected demographic and clinical information, including the time from stroke onset to treatment for those receiving reperfusion therapy, using a time-tracking table. Results Among 8069 patients with AIS, 26.6% received reperfusion therapy, with a higher proportion undergoing endovascular therapy in maritime hospitals than in inland hospitals (14.2% vs. 6.7%). Maritime hospitals had a higher prevalence of atrial fibrillation (15.1% vs. 11.9%) and cardioembolism (17.2% vs. 13.6%) than inland hospitals. Patients in maritime hospitals had shorter in-hospital processing times than those in inland hospitals (39 vs. 46 minutes). Island hospitals showed different patterns, with a shorter time from stroke onset to emergency room arrival (80 vs. 120 minutes) but a longer in-hospital process time (51 vs. 36 minutes), than coastline hospitals. Conclusions Our study suggests geographic variation in AIS characteristics and treatment processes across southeastern China, emphasizing the need for region-specific strategies. These findings are essential for tailoring public health policies and guidelines to improve stroke outcomes in various regions.

Pb83Mg17 is expected to be a potential coolant for lead cooled fast reactors because of its less toxic radioactive products and possible acceptable corrosion rate without additional oxygen control in comparison with LBE. In order to evaluate the compatibility of structural steels and Pb-Mg, two F/M steels (SIMP, T91) and two austenitic steels (316L, 15-15Ti) were tested in Pb-Mg at 350, 450 and 550 °C with exposure time ranging from 100 h to 2000 h in this work. Compared with the slight corrosion or no obvious corrosion of F/M steels, austenitic steels have suffered very serious dissolution corrosion which is significantly influenced by temperature and exposure time. The corrosion rate of austenitic steels is controlled by dissolution or diffusion mechanism at different temperatures.

Benthic diatoms have been widely utilized for assessing the ecological status of rivers, due to their ability to reflect the environmental changes from natural and anthropogenic disturbance. However, the recognized limitations of traditional morphological method for diatom identification hinder its widespread application in local department monitoring and assessment efforts. Recently, eDNA metabarcoding methods have emerged as a promising alternative for efficient diatom identification. To reveal the feasibility of eDNA metabarcoding methods in diatom-based evaluation, this study comprehensively compared them with the traditional morphological method. The results revealed that eDNA metabarcoding effectively reflected diatom composition at genus but not species level. It recognized 80.4 % of genera identified morphologically through rbcL identification and 66.7 % through 18S rDNA identification. Despite species-level discrepancies in taxonomic composition, eDNA metabarcoding accurately indicated alpha diversity of diatoms, while also provided better illustration of beta diversity. Additionally, comparisons were performed in taxonomy-based and trait-based indices. It was suggested that no significance was observed between identification methods in any index. Linear regression analyses further supported rbcL identification as a preferred option over 18S rDNA identification due to its stronger congruency with morphological method. In all, this study presented two key suggestions: 1) rbcL identification is preferable to 18S rDNA identification in diatom taxonomy, and 2) eDNA metabarcoding is proposed to be a promising technique to assess river ecological status.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations. Therefore, finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system (UPS) has emerged as a focus. The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes. In recent years, the study of UPS in hematological malignant tumors has resulted in effective treatments, such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma. In CML, the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL, interfering with CML-related signaling pathways, and negatively or positively affecting leukemia stem cells. Some of these molecules may help overcome TKI resistance and treat CML. In this review, the mechanism of TKI resistance is briefly described, the components of UPS are introduced, existing studies on UPS participating in TKI resistance are listed, and UPS as the therapeutic target and strategies are discussed.

Abstract Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. It has been implicated in various biological processes such as cell adhesion, proliferation, differentiation, and metastasis. Despite this, the precise molecular mechanisms through which CEA enhances tumor cell proliferation remain largely unclear. Our study demonstrates that CEA enhances the proliferation and migration of non-small cell lung cancer (NSCLC) while also inhibiting cisplatin-induced apoptosis in NSCLC cells. Treatment with CEA led to an increase in mitochondrial numbers and accumulation of lipid droplets in A549 and H1299 cells. Additionally, our findings indicate that CEA plays a role in regulating the fatty acid metabolism of NSCLC cells. Inhibiting fatty acid metabolism significantly reduced the CEA-mediated proliferation and migration of NSCLC cells. CEA influences fatty acid metabolism and the proliferation of NSCLC cells by activating the PGC-1α signaling pathway. This regulatory mechanism involves CEA increasing intracellular cAMP levels, which in turn activates PKA and upregulates PGC-1α. In NSCLC, inhibiting the PKA-PGC-1α signaling pathway reduces both fatty acid metabolism and the proliferation and migration induced by CEA, both in vitro and in vivo. These results suggest that CEA contributes to the promotion of proliferation and migration by modulating fatty acid metabolism. Targeting CEA or the PKA-PGC-1ɑ signaling pathway may offer a promising therapeutic approach for treating NSCLC.

This paper obtained an additively manufactured high-strength Al–Li alloy by laser powder bed fusion (LPBF) based on a third generation AA2195 alloy powder raw material. The relationship between the process optimization, microstructure evolution, and mechanical properties of the as-printed (AP) and heat-treated (HT) specimens was established for the first time to explain the intergranular fracture sensibility during LPBF and reveal the dominant precipitation strengthening mechanism induced by the subsequent heat treatment. The precipitation order of AP Al–Li alloy at the last stage of the solidification process was: L (Liquid phase) →T2 (Al6CuLi3) + θ′(Al2Cu) + δ′/β' (Al3(Li,Zr)) + T (LiAlSi) + Ω (AlCuMgAg). The micro-cracks caused by a relatively high grain boundary coverage of interconnected film-like eutectic phases, as well as micro-voids caused by the localized slip between the coarse T2-phases and soft precipitate-free zones, resulted in the high intergranular fracture sensibility. The well-designed T6 heat treatment of 515 °C/60 min solution treatment and 170 °C/6 h aging treatment was conducted to maximize the precipitation strengthening by T1-phases. The precipitation order of HT Al–Li alloy was supersaturated solid solution → GP zone + δ′/β' → θ′ + T1 (Al2CuLi) + ω (Al7Cu2Fe) + β′. The presence of continuously distributed T1-cells along the grain boundaries was not only capable of providing a pinning effect on dislocations movement and boundary migration, but also able to shorten the pile-up distance on the slip plane. Such phenomena improved the resistance ability of Al–Li alloys to mechanical damage and permitted a significant strength enhancement.

Abstract The voltage‐source virtual synchronous generator is a grid‐forming type power electronic control technology and is able to support converters that have the ability of inertial, primary frequency and voltage regulation. Firstly, the authors build the small‐signal model of the voltage‐source virtual synchronous generator and conventional converters, compare and analyse the characteristics of the high‐frequency resonance modes, the results show that the voltage‐source virtual synchronous generator has almost the same high‐frequency resonance characteristics as the conventional converter. Secondly, the different control parameters and power grid strength that affect the high‐frequency resonance characteristic are analysed with eigenvalue, and the mechanism of voltage‐source VSG that caused high‐frequency resonance is derived. The leading factor that causes high‐frequency resonance is power grid strengths, and the authors proposed introducing virtual impedance into the front‐end channel of the current inner loop control strategy to suppress resonance for the voltage‐source virtual synchronous generator based on the theoretical analysis with the small‐signal model and eigenvalue analysis. In addition, the electromagnetic transient simulation model and RT‐LAB controller‐in‐loop platform are built, and the simulation and experiment results indicate the effectiveness of the virtual impedance control strategy.

In recent years, space-division multiplexing (SDM) technology, which involves transmitting data information on multiple parallel channels for efficient capacity scaling, has been widely used in fiber and free-space optical communication systems. To enable flexible data management and cope with the mixing between different channels, the integrated reconfigurable optical processor is used for optical switching and mitigating the channel crosstalk. However, efficient online training becomes intricate and challenging, particularly when dealing with a significant number of channels. Here we use the stochastic parallel gradient descent (SPGD) algorithm to configure the integrated optical processor, which has less computation than the traditional gradient descent (GD) algorithm. We design and fabricate a 6×6 on-chip optical processor on silicon platform to implement optical switching and descrambling assisted by the online training with the SPDG algorithm. Moreover, we apply the on-chip processor configured by the SPGD algorithm to optical communications for optical switching and efficiently mitigating the channel crosstalk in SDM systems. In comparison with the traditional GD algorithm, it is found that the SPGD algorithm features better performance especially when the scale of matrix is large, which means it has the potential to optimize large-scale optical matrix computation acceleration chips.

The occurrence of coal mine rock burst disasters is closely related to the spatial structure, especially in the complex spatial structure area. It is of great significance to master the law of coal and rock catastrophe and reveal its mechanism in the complex spatial structure area of coal seam mining for the prevention and control of rock burst. Taking the Wudong Coal Mine as the research background, using numerical simulation, micro-seismic monitoring, theoretical analysis and other methods, the abnormal size effect of rock pillar stress is studied, the temporal and spatial evolution law of microseisms in the complex spatial structure area is analyzed, the mechanism of rock burst under the complex spatial structure is revealed, and the impact risk in the different areas of coal mining is evaluated. The research results show that: ① The steeply inclined rock pillar with narrower thickness and higher exposed height has stronger prying effect, and the abnormal stress of rock thickness variation forms five divisions. ② The area with narrower rock pillar thickness has more micro-seismic frequency, higher energy, stronger spatio-temporal activity and higher dispersion. The high stress region, the stress gradient region and the stress plateau region show the micro-seismic response characteristics of “low frequency-high energy”, “high frequency-high energy” and “low frequency-low energy” in turn. ③ The micro-seismic events in special spatial structure area are clustered and the energy level increases, and the temporal and spatial activity and dispersion increase sharply. This feature is more obvious especially at the edge of the structure, the energy accumulation and release rate increases, and the probability and intensity of rock burst are higher. The micro-seismic activity of special spatial structures located in the narrower area of rock pillars is more acute. ④ The narrower the thickness of rock pillar (the greater the height of coal pillar), the faster the growth rate of bending moment and energy in the depth of rock pillar, and the higher the impact risk. According to the strength effect of structural plane, it is inferred that the fault zone has slip and dislocation, and fault zone is the dominant area for energy accumulation and release. It is revealed that the mechanism of rock burst is the joint action of high static load and low critical load. The impact risk in the different areas of coal mining is evaluated based on stress concentration characteristics.

The issue of whether CoCrFeNi is a single-phase or dual-phase high-entropy alloy (HEA) has long been in dispute. In this study, CoCrFeNi has been verified to be a dual-phase HEA composed of dendritic phases with an FCC structure and inter-dendritic phases with a BCC structure. The BCC phases within inter-dendritic regions are identified as Cr3O oxides which form inevitably under the arc-melting process. Undercooling treatment under a strong magnetic field can regulate the composition and precipitation of the BCC phase, refine the grain size, and enhance the solid solubility, consequently, the mechanical performances of CoCrFeNi HEA are effectively enhanced.

The interactions between lignin oligomers and solvents determine the behaviors of lignin oligomers self-assembling into uniform lignin nanoparticles (LNPs). Herein, several alcohol solvents, which readily interact with the lignin oligomers, were adopted to study their effects during solvent shifting process for LNPs’ production. The lignin oligomers with widely distributed molecular weight and abundant guaiacyl units were extracted from wood waste (mainly consists of pine wood), exerting outstanding self-assembly capability. Uniform and spherical LNPs were generated in H2O-n-propanol cosolvent, whereas irregular LNPs were obtained in H2O-methanol cosolvent. The unsatisfactory self-assembly performance of the lignin oligomers in H2O-methanol cosolvent could be attributed to two aspects. On one hand, for the initial dissolution state, the distinguishing Hansen solubility parameter and polarity between methanol solvent and lignin oligomers resulted in the poor dispersion of the lignin oligomers. On the other hand, strong hydrogen bonds between methanol solvent and lignin oligomers during solvent shifting process, hindered the interactions among the lignin oligomers for self-assembly.

With the gradual coal mining of deep rock burst mine, the impact accompanying roadway excavation becomes more and more intense. Aiming at the problem of effective prevention and control of rock burst in roadway excavation, taking the steep seam mine in the Wudong Coal Mine as an example, the temporal and spatial precursor characteristics of rock burst in roadway excavation were analyzed by microseismic monitoring. Combined with the numerical simulation analysis of stress and energy changes in roadway excavation, the mechanism of rock burst in roadway excavation was revealed, and the prevention and control strategy of rock burst in steeply inclined extra-thick coal seam roadway was put forward, which was verified by field engineering practice. The results show that the total energy of microseisms is extremely low for 2−5 days or there is an energy latency of at least 4 days before the rock burst occurs due to roadway excavation in steeply inclined extra-thick coal seam. Within 5 days before rock burst occurs, there is a high-frequency fluctuation period of maximum energy ratio for more than 3 days. There is an obvious lack of earthquake before the rock burst occurs, and the occurrence position is concentrated in the range of minimum value of microseismic energy near the heading face, or in the range of minimum value of microseismic frequency near the extreme value of microseismic energy, and the rock burst event is located in the area with high impact deformation energy index. The hard overburden structure of horizontal sublevel fully mechanized caving mining in steeply inclined extra-thick coal seam is not easy to break, which makes the stress concentration on both sides of upper horizontal goaf exist in roadway excavation. The stress between the front of the heading face and the bottom of the roadway squeezed by the roof and floor strata is concentrated and the energy accumulation is remarkable. With the increase of the heading depth of the roadway, the stress concentration and energy accumulation are further enhanced, which is easy to induce dynamic disasters such as rock burst. The prevention and control strategies of rock burst was established through comprehensive analysis, which consist of face blasting pressure relief, roadway drilling pressure relief and reinforcement support, and scaffolding in complex areas. Combined with the temporal and spatial precursory anomalies of rock burst, it provides an opportunity to strengthen the unloading pressure in time. Through the pressure relief of working face and roadway, the accumulated microseismic energy of more than 1×105 J per day did not occur during the excavation. After the support was optimized and the complex area was protected, the daily average microseismic energy of roadway excavation decreased to 2.2 kJ, and the proportion of microseismic events above 1 kJ decreased, and the overall section of roadway was flat.

Abstract Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing.

Abstract Background Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. Methods and results miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. Conclusions Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Abstract The damage to the back of the target plate is a phenomenon that occurs when concrete is subjected to high-speed impact. In order to study the motion parameters of prefabricated spherical fragments penetrating finite thickness concrete targets at high speeds and the occurrence rules of concrete damage, as well as the impact of target back damage on the motion of fragments, experiments were conducted on 100 mm finite thickness concrete targets with prefabricated spherical fragments. The concrete model parameters in LS-DYNA were modified based on the residual velocity of fragments, and numerical simulations were conducted on the penetration of prefabricated fragments with different impact velocities and concrete target plates with different thicknesses. By analyzing the location of concrete target plate damage, the relationship between concrete thickness and concrete damage was obtained; Combining the motion parameters of fragment penetration process, the phenomenon of concrete collapse was linked to fragment motion, and the influence of concrete thickness on fragment motion parameters was analyzed. The results indicate that the thickness of the finite thickness concrete target plate and the penetration speed of fragments have a significant impact on the damage state of the target back, and further affect the motion change response stage during the penetration process of prefabricated fragments.

Abstract Background Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. Objective The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. Methods An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. Results We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). Conclusion The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

ABSTRACTThis study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12–46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

AimThis study aims to explore the effectiveness and safety of Ginkgolide® in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) and moderate-to-severe stroke receiving intravenous alteplase thrombolysis (IVT).MethodsGinkgolide with Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function (GIANT) was an open-label, prospective, multicenter, cluster-randomized clinical trial and included AIS patients in 24 centers randomized to the intervention of intravenous Ginkgolide® or control group within the first 24 h after IVT. LVO was defined as any occlusion of the internal carotid artery, M1 or M2 of the middle cerebral artery, A1 or A2 of the anterior cerebral artery, P1 of the posterior cerebral artery, and V4 of the vertebral artery or the basilar artery. Stroke severity was assessed with the National Institutes of Health Stroke Scale (minor ≤5; moderate-to-severe >5). The primary outcome was a good outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days. Secondary outcomes were early neurological improvement (ENI), defined as ≥18% increase in the National Institutes of Health Stroke Scale (NIHSS) score at 7 days compared to baseline and distribution of mRS at 3 months.ResultsA total of 1,113 patients were included, with 268/913 (29.4%) presenting LVO and 508 (45.6%) presenting moderate-to-severe stroke. In patients with LVO, Ginkgolide® usage was independently associated with ENI (P = 0.001) but not with a good outcome (P = 0.154). In the moderate-to-severe stroke subgroup, Ginkgolide® was independently associated with both a good outcome (P = 0.009) and ENI (P = 0.028). Ginkgolide® did not increase the risk of hemorrhagic transformation (all P > 0.05).ConclusionUsing Ginkgolide® within 24-h after intravenous rt-PA is effective and safe in LVO and moderate-to-severe stroke patients.

Abstract Wound infections pose a major healthcare issue, affecting the well‐being of millions of patients worldwide. Effective intervention and on‐site detection are important in wound management. However, current approaches are hindered by time‐consuming analysis and a lack of technology for real‐time monitoring and prompt therapy delivery. In this study, a smart wound patch system (SWPS) designed for wireless closed‐loop and in‐situ wound management is presented. The SWPS integrates a microfluidic structure, an organic electrochemical transistor (OECT) based sensor, an electrical stimulation module, and a miniaturized flexible printed circuit board (FPCB). The OECT incorporates a bacteria‐responsive DNA hydrogel‐coated gate for continuous monitoring of bacterial virulence at wound sites. Real‐time detection of OECT readings and on‐demand delivery of electrical cues to accelerate wound healing is facilitated by a mobile phone application linked with an FPCB containing low‐power electronics equipped with parallel sensing and stimulation circuitry. In this proof‐of‐concept study, the functionality of the SWPS is validated and its application both in vitro and in vivo is demonstrated. This proposed system expands the arsenal of tools available for effective wound management and enables personalized treatment.

Self-synchronizing voltage source inverter (SSVSI) can effectively improve grid frequency stability. However, the synchronous frequency resonance (SFR) inevitably exists in SSVSI. In this paper, a small-signal model considering power coupling is established to analyze the system characteristics. It is found that the control parameter adjustment and the virtual resistance method can suppress the SFR. However, the control parameter adjustment will change the dynamic and steady-state characteristics of the system, and the virtual resistance method will exacerbate the power coupling of the system. For this reason, based on the idea of eliminating the resonance peaks, this paper proposes an SFR suppression method based on band-stop filters. By connecting band-stop filters in series in the active power control loop (APCL) and the reactive power control loop (RPCL), the proposed method effectively suppresses the resonance peaks without changing the original control parameters of the system, and the control bandwidth is wider, which improves the power response speed of the system. In addition, the proposed method avoids exacerbating the power coupling of the system compared with the virtual resistance method. Finally, the simulation and experimental results verify the correctness of the theoretical analysis and the effectiveness of the control method.

Abstract Structural materials such as ceramics, metals, and carbon fiber‐reinforced plastics (CFRP) are frequently threatened by large compressive and impact forces. Energy absorption layers, i.e., polyurethane and silicone foams with excellent damping properties, are applied on the surfaces of different substrates to absorb energy. However, the amount of energy dissipation and penetration resistance are limited in commercial polyurethane foams. Herein, a distinctive nacre‐like architecture design strategy is proposed by integrating hard porous ceramic frameworks and flexible polyurethane buffers to improve energy absorption and impact resistance. Experimental investigations reveal the bioinspired designs exhibit optimized hardness, strength, and modulus compared to that of polyurethane. Due to the multiscale energy dissipation mechanisms, the resulting normalized absorbed energy (≈8.557 MJ m−3) is ≈20 times higher than polyurethane foams under 50% quasi‐static compression. The bioinspired composites provide superior protection for structural materials (CFRP, glass, and steel), surpassing polyurethane films under impact loadings. It is shown CFRP coated with the designed materials can withstand more than ten impact loadings (in energy of 10 J) without obvious damage, which otherwise delaminates after a single impact. This biomimetic design strategy holds the potential to offer valuable insights for the development of lightweight, energy‐absorbent, and impact‐resistant materials.

The purpose of this study is to put forward a feature extraction and pattern recognition method for the flow noise signal of natural gas pipelines in view of the complex situation brought by the rapid development and expansion of urban natural gas infrastructure in China, especially in the case that there are active and abandoned pipelines, metal and nonmetal pipelines, and natural gas, water and power pipelines coexist in the underground of the city. Because the underground situation is unknown, gas leakage incidents caused by natural gas pipeline rupture occur from time to time, posing a threat to personal safety. Therefore, the motivation of this study is to provide a feasible method to accelerate the aging, renewal and transformation of urban natural gas pipelines to ensure the safe operation of urban natural gas pipeline network and promote the high-quality development of urban economy. Through the combination of experimental test and numerical simulation, this study establishes a database of urban natural gas pipeline flow noise signals, and uses principal component analysis (PCA) to extract the characteristics of flow noise signals, and develops a mathematical model for feature extraction. Then, a classification and recognition model based on backpropagation neural network (BPNN) is constructed, which realizes the detection and recognition of convective noise signals. The research results show that the theoretical method based on acoustic feature analysis provides guidance for the orderly and safe construction of urban natural gas pipeline network and ensures its safe operation. The research conclusion shows that through the simulation analysis of 75 groups of gas pipeline flow noise under different working conditions. Combined with the experimental verification of ground flow noise signals, the feature extraction and pattern recognition method proposed in this study has a recognition accuracy of up to 97% under strong noise background, which confirms the accuracy of numerical simulation and provides theoretical basis and technical support for the detection and recognition of urban gas pipeline flow noise.