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Abstract Background Fibrosis is the ultimate, common pathological ending of most chronic inflammatory diseases and increases the chances of developing life-threatening illnesses. Pyroptosis, a newfound form of lytic programmed cell death initiated by the inflammasome, has received more and more attention because of its association with fibrotic diseases. Therefore, this study visualizes the connection between pyroptosis and fibrosis research through bibliometric methods, aimed at providing global research hits and tendencies in the field. Methods We collected and analyzed the articles on pyroptosis and fibrosis from 2010 to 2024 via Web of Science. Visual data analysis was performed for countries, institutions, authors, references, and keywords in the field using VOSviewer, CiteSpace software, the “Bibliometrix” R package, the bibliometric website ( https://bibliometric.com/ ), and Excel software. We analyzed the data by utilizing the bibliometric review method. Results A total of 566 articles and reviews relating to pyroptosis and fibrosis were identified in the Web of Science. The number of publications in the domain has continued to grow since 2010. These scientific outputs were mainly from 129 countries/regions and 1919 institutions, particularly China (n = 423) and the USA (n = 83). More importantly, although China publishes a vast majority of articles, its centrality is lower than that of the USA (0.59 vs 0.61). Among the 3833 authors involved in this field, Feldstein, A. E. is the most prolific author. Shi, J. J. is the world’s most-cited author among the 12,143 authors in these academic journals. Frontiers in Immunology was a prolific contributor, and Nature was the most frequently cited journal. After analysis, Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death were the top-cited articles. The analysis of keywords displayed that pyroptosis, fibrosis, and pathways were the main research hotspots and frontier directions in recent years. Conclusion We analyzed the characteristics of published articles and drew a fundamental knowledge structure on pyroptosis and fibrosis research via bibliometric analysis. The potential mechanism between fibrosis and pyroptosis is deeply tied to the current moment. Our findings can help researchers make clear the research status and value of fibrosis and pyroptosis and provide new directions for future research as soon as possible.

Abstract Normal life requires cell division to produce new cells, but cell death is necessary to maintain balance. Dysregulation of cell death can lead to the survival and proliferation of abnormal cells, promoting tumor development. Unlike apoptosis, necrosis, and autophagy, the newly recognized forms of regulated cell death (RCD) cuproptosis, ferroptosis, and PANoptosis provide novel therapeutic strategies for tumor treatment. Increasing research indicates that the death of tumor and immune cells mediated by these newly discovered forms of cell death can regulate the tumor microenvironment (TME) and influence the effectiveness of tumor immunotherapy. This review primarily elucidates the molecular mechanisms of cuproptosis, ferroptosis, and PANoptosis and their complex effects on tumor cells and the TME. This review also summarizes the exploration of nanoparticle applications in tumor therapy based on in vivo and in vitro evidence derived from the induction or inhibition of these new RCD pathways.

Abstract Following the publication of the 2021 WHO Classification of Central Nervous System Tumors (CNS5), Following the publication of the 2021 WHO Classification of Central Nervous System Tumors (CNS5), prognostic markers of glioblastoma (GBM) need to be further explored. Radiomics is a non-invasive and reproducible method for the prognostic assessment of multiple solid tumors. This study aimed to explore the prognostic value and biological significance of MRI T1-weighted enhancement (CE-T1) based radiomics in GBM (CNS5). A six-features radiomics prognostic model was created to calculate the radiomics score (RS). High RS (HR = 3.718, 95%CI: 2.222 − 6.220, P

Abstract Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.

Abstract Liquid crystal networks (LCN) have attracted surging interest as extraordinary energy-dissipation materials owning to their unique dissipation mechanism based on the re-orientation of mesogens. However, how to integrate high Young’s modulus, good dissipation efficiency and wide effective damping temperature range in energy-dissipation LCN remains a challenge. Here, we report a strategy to resolve this challenge by fabricating robust energy-dissipation liquid crystal semi-interpenetrating polymer network (LC-semi-IPN) consisting crystalline LC polymers (c-LCP). LC-semi-IPN demonstrates a superior synergistic performance in both mechanical and energy-dissipation properties, surpassing all currently reported LCNs. The crystallinity of c-LCP endows LC-semi-IPN with a substantial leap in Young’s modulus (1800% higher than single network). The chain reptation of c-LCP also promotes an enhanced dissipation efficiency of LC-semi-IPN by 200%. Moreover, its effective damping temperature reaches up to 130 °C, which is the widest reported for LCNs. By leveraging its exceptional synergistic performance, LC-semi-IPN can be further utilized as a functional architected structure with exceptional energy-dissipation density and deformation-resistance.

Abstract Background We investigated the association between sleep problems and cardiometabolic risks and the potential linking effect of metabolites and metabolic pathways based on multi-layered research, including observational, mendelian randomization (MR), and metabolomics analysis. Methods A cross-sectional analysis of the 2015–2018 National Health and Nutrition Examination Survey (NHANES) dataset was conducted to identify the association between sleep problems and cardiometabolic risks. A subsequent MR study based on genetic data was performed to explore the causal correlation of significant associations in the NHANES study. The underlying alteration of metabolism was explored by constructing zebrafish models and wide-targeted metabolomics analysis. Results The cross-sectional analysis of the NHANES database revealed a significant association of snoring with obesity [OR = 2.65, 95% confidence intervals (CI): 1.87, 3.74]; sleep apnea with hypertension (OR = 1.68, 95% CI: 1.14, 2.48) and obesity (OR = 1.44, 95% CI: 1.05, 1.96); trouble sleeping with hypertension (OR = 1.84, 95% CI: 1.18, 2.86), obesity (OR = 1.56, 95% CI: 1.07, 2.26), and type 2 diabetes (T2DM) (OR = 1.52, 95% CI: 1.02, 2.25). MR analysis verified the causal relationship between genetically proxied sleep apnea or snoring and obesity. The decreased activity levels and altered expression levels of six circadian genes (bmal1b, cry1aa, cry1ab, clock1a, per1b, per2) were identified in the zebrafish of the sleep disorder group. Multiple metabolites related to disturbed glucose metabolism (e.g., 20-HETE), lipid metabolism (e.g., inosine), and vascular-related metabolites (e.g., riboflavin) were finally identified, indicating the latent effect of metabolism. Conclusions This study identified the chain of sleep-circadian rhythm-metabolism-cardiometabolic risks. These findings can promote improved prevention implementation and therapeutic strategies.

As the information technology develops, educational resource recommendation system has become an indispensable part of the education field. At the same time, people’s demand for personalised educational resources is also growing; therefore, how to accurately predict user demand and provide personalised recommendations has become an important issue. In this study, a fuzzy predictive control model on the grounds of neural network is proposed to optimise the design of educational resource recommendation in the context of information technology. After experimental testing, the model recommendation fit reached 95.16 and 92.91% on the two test datasets, which are significantly higher than the control model. The average F1 values of the proposed model also reached 95.21 and 88.77%, which are higher than the control model. In other control experiments, the proposed model of this study also has a better performance. The relevant outcomes showcase that the predictive performance and recommendation effect of the model can be further enhanced by improving the structure of the neural network and the parameter optimisation method. Meanwhile, the proposed model has high performance in information overload and personalised demand, which offers a useful reference for the optimal design of educational resource recommendation system.

Abstract Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P

With the popularization of high-resolution thin-layer CT, the detection rate of early asymptomatic lung cancer that manifests as solitary pulmonary nodules has significantly increased. The differentiation of benign from malignant nodules and histopathological classification are the keys to and challenges of clinical diagnoses, the accuracy of which is of great significance for treatment decision-making. Traditional CT evaluates nodules based on their size, density, and morphological characteristics with single modal imaging. Dual-energy CT achieves material separation based on attenuation differences in the same tissue at two different energy levels, which allows CT imaging to evolve from a single-parameter to multi-parameter measurements. This not only provides more valuable information for the early and accurate diagnosis of nodules but also facilitates measurements of tumor progression and heterogeneity. In addition, the combination of radiomics based on artificial intelligence and multi-parameter images by dual-energy CT has shown great potential in diagnosis, and the related investigations are in exploratory stages. This review will cover the application of dual-energy CT in the diagnosis of solitary pulmonary nodules, with a focus on the meaning of multi-parameter images for the ccurate diagnosis of pulmonary nodules. Further, the future directions of this diagnostic imaging technique are discussed as well.

Abstract Rechargeable aqueous zinc-metal batteries, considered as the possible post-lithium-ion battery technology for large-scale energy storage, face severe challenges such as dendrite growth and hydrogen evolution side reaction (HER) on Zn negative electrode. Herein, a three-dimensional Cu-In alloy interface is developed through a facile potential co-replacement route to realize uniform Zn nucleation and HER anticatalytic effect simultaneously. Both theoretical calculations and experimental results demonstrate that this bifunctional Cu-In alloy interface inherits the merits of low Zn-nucleation overpotential and high HER overpotential from individual copper and indium constituents, respectively. Moreover, the dynamical self-reconstruction during cycling leads to an HER-anticatalytic and zincophilic gradient hierarchical structure, enabling highly reversible Zn chemistry with dendrite-free Zn (002) deposition and inhibited HER. Moreover, the improved interface stability featured by negligible pH fluctuations in the diffusion layer and suppressed by-product formation is evidenced by in-situ scanning probe technology, Raman spectroscopy, and electrochemical gas chromatography. Consequently, the lifespan of the CuIn@Zn symmetric cell is extended to more than one year with a voltage hysteresis of 6 mV. Importantly, the CuIn@Zn negative electrode is also successfully coupled with high-loading iodine positive electrode to fabricate Ah-level (1.1 Ah) laminated pouch cell, which exhibits a capacity retention of 67.9% after 1700 cycles.

Rock blasting technology is crucial for national economic development, particularly resource extraction and infrastructure construction. This paper explores the constitutive relationships in rock blasting, proposing three evolutionary stages: constitutive relationships 1.0, 2.0, and 3.0. These stages focus on contradictory relationships, energy balance, and minimum action theory, respectively. Constitutive relationship 1.0 centers on the interaction between rock and explosive impact loads, emphasizing the offense–defense dynamic. It analyzes the dynamic mechanical response of rock materials under explosive and impact loads, highlighting the conflict and balance between the explosive force and the rock resistance. This stage provides fundamental insights into the behavior of rock materials under high-stress conditions. Constitutive relationship 2.0 approaches the problem from an energy perspective. It treats rocks with significant anisotropy, joints, fractures, bedding, and cavities as complex structural materials. This stage studies the dynamic equilibrium between load input energy and the energy required to destroy the material. By understanding the relationship between structural strength, input energy, dissipated energy, and releasable strain energy, researchers can better predict the response of complex rock structures to explosive loads and improve blasting efficiency. Constitutive relationship 3.0 examines the propagation laws of stress waves under explosive loads and their relationship with medium damage effects. This stage focuses on optimizing energy propagation paths based on the minimum action theory, aiming to maximize the effectiveness of the explosive force while minimizing unwanted damage to the surrounding rock mass. These theories not only reveal the mechanical behavior of rocks under different load conditions but also provide a theoretical basis for optimizing blasting design and improving blasting outcomes. In addition to these theoretical advancements, the integration of artificial intelligence and big data technologies offers a new approach to managing and predicting rock material performance. This paper proposes the concept of rock material engineering genes, which involves establishing a rock gene library to systematically manage the physical and mechanical parameters of rocks. By constructing performance prediction models using advanced data analytics and machine learning algorithms, this approach enhances the accuracy of predicting how different rock types will respond to various engineering applications. Such a comprehensive database has significant implications for resource extraction, geological disaster prevention, and infrastructure construction. The rock material gene library is expected to play an increasingly important role in mineral resource development, geological disaster prevention, and infrastructure construction, thereby promoting the development and application of engineering technology. Its integration with traditional blasting techniques can lead to more efficient and safer methods of rock blasting, ultimately contributing to the advancement of engineering practices and economic development of regions dependent on these technologies. This holistic approach underscores the importance of continued research and technological innovation in rock blasting and material science.

Abstract Cinnamomum cassia Presl. is a subtropical plant that is used for food and medicine. Climate change has changed the suitable habitats of medicinal plants, which might have repercussions for the efficacy of herbal remedies. In this study, the potential distribution in each period of Cinnamomum cassia was predicted and the quality in different suitable habitats was evaluated. According to the results, (1) precipitation, temperature, and soil are the primary environmental variables influencing C. cassia distribution. (2) The high-suitable habitats of current climate scenarios were predominantly located in the southern regions (Guangdong and Guangxi etc.) of China, with an area of 706,129.08 km2. Under future climate scenarios, suitable habitats will increasingly move northward, with a greater concentration south of the Yangtze River, particularly in the 2090s SSP585 scenario, the total area of newly extended suitable habitat reaches 312,963.53 km2. (3) HPLC and FTIR, combined with chemometrics, can be effective methods for identifying different suitable habitats of C. cassia. The content of trans-cinnamaldehyde (0.85%) is significantly higher in the high suitability habitat compared to the medium-low suitability habitat (0.30%). Our findings can offer valuable guidance for the identification of suitable C. cassia cultivation areas in China, as well as for the evaluation of C. cassia resource quality and the rational use of resources in different suitable habitats.

Abstract Background Lifestyle intervention is the first-line treatment for PCOS. Numerous studies have investigated the effect of various lifestyle factors, including dietary habit, smoking, and alcohol consumption on PCOS women. These studies have found that such factors may be associated with physiological parameters such as androgen, and emotional states like anxiety or depression. Smoking, a harmful lifestyle habit widely recognized to contribute to various diseases, has also been found to be related to PCOS. Current research has not adequately compared the effects of smoking with other lifestyle habits on PCOS, and there is little mention of its relationship with the emotional states of patients with PCOS. To further elucidate the association between smoking and other lifestyle factors with clinical symptoms in patients with PCOS, we conducted a cross-sectional evaluation using data from Peking University Third Hospital, with a special focus on analyzing smoking habits and comparing it with a variety of lifestyle factors. Methods This cross-sectional study included 601 PCOS women and 184 healthy controls who underwent physical examinations, hormone profiles and psychological measures. We assessed the association between smoking and the clinical symptoms in PCOS women. Results We found a significant correlation between smoking and the degree of depression in PCOS women among the three emotional states: anxiety, depression, and stress. Smoking was also significantly associated with testosterone level in PCOS participants, suggesting that PCOS women who smoke exhibited more severe depressive symptoms and higher testosterone level. In addition, compared to the control group, PCOS women had notably higher testosterone (T) and luteinizing hormone (LH) levels. Smoke and alcohol were statistically significantly more common in women with PCOS than the Control. Conclusion Women with PCOS who smoke were found to have elevated testosterone levels and more severe depression. These findings suggest that clinicians should monitor smoking women with PCOS for symptoms of depression and assess their hyperandrogenic status.

Abstract Background Multiple models intravoxel incoherent motion (IVIM) based 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance(18F-FDG PET/MR) could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored. Objective To compare the value of 18F-FDG PET/MR metabolic parameters and diffusion parameters in the prognostic assessment of patients with NSCLC. Meterial and methods Chest PET and IVIM scans were performed on 61 NSCLC patients using PET/MR. The maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), diffusion coefficient (D), perfusion fraction (f), pseudo diffusion coefficient (D*) and apparent diffusion coefficient (ADC) were calculated. The impact of SUVmax, MTV, TLG, D, f, D*and ADC on survival was measured in terms of the hazard ratio (HR) effect size. Overall survival time (OS) and progression-free survival time (PFS) were evaluated with the Kaplan–Meier and Cox proportional hazard models. Log-rank test was used to analyze the differences in parameters between groups. Results 61 NSCLC patients had an overall median OS of 18 months (14.75, 22.85) and a median PFS of 17 months (12.00, 21.75). Univariate analysis showed that pathological subtype, TNM stage, surgery, SUVmax, MTV, TLG, D, D* and ADC were both influential factors for OS and PFS in NSCLC patients. Multifactorial analysis showed that MTV, D* and ADC were independent predicting factors for OS and PFS in NSCLC patients. Conclusion MTV, D* and ADC are independent predicting factors affecting OS and PFS in NSCLC patients. 18F-FDG PET/MR-derived metabolic parameters and diffusion parameters have clinical value for prognostic assessment of NSCLC patients.

Abstract With the continuous advance of coal mining, the normal stress in front of coal seams will continue to increase, resulting in changes of internal structure and permeability of coal seams. During the continuous advance of mining face, the increase of vertical stress somewhere in front of coal seams may not be a transient process, but a gradual change process. Therefore, this paper carried out the seepage test of gas-containing coal under discontinuous loading axial stress. The stress, deformation and permeability of coal specimens were measured and recorded during the test, and the influence of discontinuous loading axial stress on the deformation, internal structure and seepage properties of coal specimens were discussed. On this basis, considering the influence of stress on the gas adsorption state, Klinkenberg effect and other factors, combined with Shi-Durucan permeability model, a new permeability model considering the dynamic adsorption state of coal specimens was developed.

Abstract The presence of microplastics within the human body has raised significant concerns about their potential health implications. Numerous studies have supported the hypothesis that the accumulation of microplastics can trigger inflammatory responses, disrupt the microbiome, and provoke immune reactions due to their physicochemical properties. Chronic inflammation, characterized by tissue damage, angiogenesis, and fibrosis, plays a crucial role in cancer development. It influences cancer progression by altering the tumor microenvironment and impairing immune surveillance, thus promoting tumorigenesis and metastasis. This review explores the fundamental properties and bioaccumulation of microplastics, as well as their potential role in the transition from chronic inflammation to carcinogenesis. Additionally, it provides a comprehensive overview of the associated alterations in signaling pathways, microbiota disturbances, and immune responses. Despite this, the current understanding of the toxicity and biological impacts of microplastics remains limited. To mitigate their harmful effects on human health, there is an urgent need to improve the detection and removal methods for microplastics, necessitating further research and elucidation.

Abstract The field of photonic integrated circuits has witnessed significant progress in recent years, with a growing demand for devices that offer high-performance reconfigurability. Due to the inability of conventional tunable directional couplers (TDCs) to maintain a fixed phase while tuning the reflectivity, Mach-Zehnder interferometers (MZIs) are employed as the primary building blocks for reflectivity tuning in constructing large-scale circuits. However, MZIs are prone to fabrication errors due to the need for perfect balanced directional couplers to achieve 0-1 reflectivity, which hinders their scalability. In this study, we introduce a design of a TDC based on coupling constant tuning in the thin film Lithium Niobate platform and present an optimized design. Our optimized TDC design enables arbitrary reflectivity tuning while ensuring a consistent phase across a wide range of operating wavelengths. Furthermore, it exhibits fewer bending sections than MZIs and is inherently resilient to fabrication errors in waveguide geometry and coupling length compared to both MZIs and conventional TDCs. Our work contributes to developing high-performance photonic integrated circuits with implications for various fields, including optical communication systems and quantum information processing.

Abstract The influenza neuraminidase (NA) is a potential target for the development of a next-generation influenza vaccine, but its antigenicity is not well understood. Here, we isolate an anti-N6 human monoclonal antibody, named 18_14D, from an H5N6 avian influenza virus (AIV) infected patient. The antibody weakly inhibits enzymatic activity but confers protection in female mice, mainly via ADCC function. The cryo-EM structure shows that 18_14D binds to a unique epitope on the lateral surface of the N6 tetramer, preventing the formation of tightly closed NA tetramers. These findings contribute to the molecular understanding of protective immune responses to NA of AIVs in humans and open an avenue for the rational design of NA-based vaccines.

Abstract Peptide surfactants have been extensively investigated with various applications in detergents, foods, and pharmaceutics due to their biodegradability, biocompatibility, and customizable structures. Traditional peptide surfactants are often designed in a head-to-tail fashion mimicking chemical surfactants. Alternatively, a side-by-side design pattern based on heptad repeats offers an approach to designing peptide surfactants. However, minimalist peptide design using a single heptad for stabilizing interfaces remains largely unexplored. Here, we design four heptad surfactants (AM1.2, 6H, 6H7K, and HK) responsive to metal ions and compare their emulsification performance with a three-heptad peptide, AM1. Among them, the HK peptide generates emulsions exhibiting good stability over months. We further optimize factors such as buffering salts, ionic strength, and emulsion dilutions to uncover their impacts on emulsion properties. Our findings deepen the understanding of emulsion properties and provide practical insights for characterizing peptide-based emulsions, paving the way for their broader utilization in diverse applications.

Abstract The full life-cycle state monitoring of bridge structures is an effective way to ensure traffic safety and is also an important trend in the development of modern transportation. The accuracy, traceability, and reliability of sensor data are the foundation for the Bridge Health Monitoring (BHM) system to achieve its various functions. However, commonly seen uncertainties in measurement results of the monitoring system such as error, linearity, and repeatability often need to be calibrated to ensure accuracy and reliability of the data. Therefore, the calibration of these basic uncertain elements has been brought to our research focus. In this study, we first comb the monitoring parameters and characteristics of different sensor systems to help select suitable bridge structure monitoring sensors and adopt appropriate calibration and traceability strategies. Then, in combination with the research on traditional sensor calibration techniques and new sensor calibration technology, we present the key factors to be considered in the sensor calibration process and the challenges faced by the current technologies. Finally, suggestions are made for the research trend on the calibration of bridge monitoring sensors, aiming to provide reference for both theoretical and practical studies on bridge sensor calibration in the future.

Abstract Background Children with atrial septal defect (ASD) and ventricular septal defect (VSD) are frequently examined for respiratory symptoms, even when the underlying disease is not found. Chest radiographs often serve as the primary imaging modality. It is crucial to differentiate between ASD and VSD due to their distinct treatment. Purpose To assess whether deep learning analysis of chest radiographs can more effectively differentiate between ASD and VSD in children. Methods In this retrospective study, chest radiographs and corresponding radiology reports from 1,194 patients were analyzed. The cases were categorized into a training set and a validation set, comprising 480 cases of ASD and 480 cases of VSD, and a test set with 115 cases of ASD and 119 cases of VSD. Four deep learning network models—ResNet-CBAM, InceptionV3, EfficientNet, and ViT—were developed for training, and a fivefold cross-validation method was employed to optimize the models. Receiver operating characteristic (ROC) curve analyses were conducted to assess the performance of each model. The most effective algorithm was compared with the interpretations provided by two radiologists on 234 images from the test group. Results The average accuracy, sensitivity, and specificity of the four deep learning models in the differential diagnosis of VSD and ASD were higher than 70%. The AUC values of ResNet-CBAM, IncepetionV3, EfficientNet, and ViT were 0.87, 0.91, 0.90, and 0.66, respectively. Statistical analysis showed that the differential diagnosis efficiency of InceptionV3 was the highest, reaching 87% classification accuracy. The accuracy of InceptionV3 in the differential diagnosis of VSD and ASD was higher than that of the radiologists. Conclusions Deep learning methods such as IncepetionV3 based on chest radiographs in the study showed good performance for differential diagnosis of congenital VSD and ASD, which may be able to assist radiologists in diagnosis, education, and training, and reduce missed diagnosis and misdiagnosis.

Abstract Background Ferroptosis, a newly identified form of regulated cell death triggered by small molecules or specific conditions, plays a significant role in virus-associated carcinogenesis. However, whether tumours arising after high-risk HPV integration are associated with ferroptosis is unexplored and remains enigmatic. Methods High-risk HPV16 integration was analysed by high­throughput viral integration detection (HIVID). Ferroptosis was induced by erastin, and the levels of ferroptosis were assessed through the measurement of lipid-reactive oxygen species (ROS), malondialdehyde (MDA), intracellular Fe2+ level and transmission electron microscopy (TEM). Additionally, clinical cervical specimens and an in vivo xenograft model were utilized for the study. Results Expression of HPV16 integration hot spot c-Myc negatively correlates with ferroptosis during the progression of cervical squamous cell carcinoma (CSCC). Further investigation revealed that the upregulated oncogene miR-142-5p in HPV16-integrated CSCC cells served as a critical downstream effector of c-Myc in its target network. Inhibiting miR-142-5p significantly decreased the ferroptosis-suppressing effect mediated by c-Myc. Through a combination of computational and experimental approaches, HOXA5 was identified as a key downstream target gene of miR-142-5p. Overexpression of miR-142-5p suppressed HOXA5 expression, leading to decreased accumulation of intracellular Fe2+ and lipid peroxides (ROS and MDA). HOXA5 increased the sensitivity of CSCC cells to erastin-induced ferroptosis via transcriptional downregulation of SLC7A11, a negative regulator of ferroptosis. Importantly, c-Myc knockdown increased the anti-tumour activity of erastin by promoting ferroptosis both in vitro and in vivo. Conclusions Collectively, these data indicate that HPV16 integration hot spot c-Myc plays a novel and indispensable role in ferroptosis resistance by regulating the miR-142-5p/HOXA5/SLC7A11 signalling axis and suggest a potential therapeutic approach for HPV16 integration-related CSCC.

Abstract Increasing urban density promotes a greater social role for cities. The current low-carbon city development goals put forward higher requirements for carbon performance. Based on the viewpoint of minimizing natural resource input and maximizing value acquisition in ecological benefits, the influence of urban density on spatial carbon performance is analyzed by polynomial function relationship, and Beijing and Shanghai with different urban function positioning are taken as examples for comparative analysis. Combined with Point-of-Interest (POI), the classification benchmark of industrial activities was established, and the spatial kernel density of ArcGIS software was used to analyze the industrial agglomeration characteristics of the two cities. The results show that: 1) The “increase-decrease-increase-decrease” trend of urban spatial carbon performance over time fluctuates around the unary linear trend of urban density.2) Population and building density are too low or too high, which is not conducive to emission reduction. The change of economic density is influenced by the industrial structure. The change of urban density is negatively correlated with the growth rate of spatial carbon performance. In a certain development stage, the increase of urban density will inhibit the growth of spatial carbon performance to some extent. 3) Maintaining the original economic and industrial structure, the increase in economic density brought by the simple expansion of scale is not conducive to emission reduction. The increase of economic density brought by the transformation of economic or industrial structure and the reduction of the proportion of secondary industry is conducive to urban emission reduction.

Abstract Gastric premalignant lesions can develop into cancer through multiple steps and inflammation plays a critical role. The aim of this study is to uncover the characteristics of macrophages and their gene expression in premalignant gastric lesions to identify novel biomarkers and potential targets for treatment. We used the computational algorithm CIBERSORT to estimate immune cell subsets present in gastric tissue. We applied WGCNA to identify inflammation-related modules and hub genes. Single-cell analysis was used to identify macrophage sub-clusters specific to pathology. In addition, the in-vitro experiment was performed to verify the mechanism of the key inflammatory factors in the growth of gastric cancer. WGCNA identified a module that was positively correlated with pathological changes and highly related to inflammation scores. Single-cell analysis revealed a macrophage subset, and we observed that S100A8 and S100A9 + macrophages made up a significantly higher proportion in early gastric cancer (EGC) tissues. Our functional enrichment analysis suggested that these macrophages may play a role in gastric tumorigenesis through the activation of the NFκB signaling pathway. In vitro experiments verified that S100A9 can promote the proliferation and migration of AGS cells through the TLR4-NFκB signaling pathway, and the S100A8/S100A9 inhibitor Paquinimod can inhibit their proliferation and migration. Our findings suggest that S100A8 and S100A9 + macrophages may activate the TLR4-NFκB signaling pathway to promote cell proliferation and migration leading to gastric tumor progression. Macrophages with high expression of S100A8/S100A9 are critical in the progression of gastric inflammation to cancer. Cytokine S100A9 can activate the TLR4-NFκB signaling pathway and promote the proliferation and migration of gastric adenocarcinoma cells.

Abstract Promoters play a crucial role in regulating gene transcription. However, our understanding of how genetic variants influence alternative promoter selection is still incomplete. In this study, we implement a framework to identify genetic variants that affect the relative usage of alternative promoters, known as promoter usage quantitative trait loci (puQTLs). By constructing an atlas of human puQTLs across 49 different tissues from 838 individuals, we have identified approximately 76,856 independent loci associated with promoter usage, encompassing 602,009 genetic variants. Our study demonstrates that puQTLs represent a distinct type of molecular quantitative trait loci, effectively uncovering regulatory targets and patterns. Furthermore, puQTLs are regulating in a tissue-specific manner and are enriched with binding sites of epigenetic marks and transcription factors, especially those involved in chromatin architecture formation. Notably, we have also found that puQTLs colocalize with complex traits or diseases and contribute to their heritability. Collectively, our findings underscore the significant role of puQTLs in elucidating the molecular mechanisms underlying tissue development and complex diseases.

Abstract Morphogenesis requires building stable macromolecular structures from highly dynamic proteins. Muscles are anchored by long-lasting integrin adhesions to resist contractile force. However, the mechanisms governing integrin diffusion, immobilization, and activation within developing tissues remain elusive. Here, we show that actin polymerization-driven membrane protrusions form nanotopographies that enable strong adhesion at Drosophila muscle attachment sites (MASs). Super-resolution microscopy reveals that integrins assemble adhesive belts around Arp2/3-dependent actin protrusions, forming invadosome-like structures with membrane nanotopographies. Single protein tracking shows that, during MAS development, integrins become immobile and confined within diffusion traps formed by the membrane nanotopographies. Actin filaments also display restricted motion and confinement, indicating strong mechanical connection with integrins. Using isolated muscle cells, we show that substrate nanotopography, rather than rigidity, drives adhesion maturation by regulating actin protrusion, integrin diffusion and immobilization. These results thus demonstrate that actin-polymerization-driven membrane protrusions are essential for the formation of strong integrin adhesions sites in the developing embryo, and highlight the important contribution of geometry to morphogenesis.

Abstract Background Despite significant progress in the prognosis of pediatric T-cell acute lymphoblastic leukemia (T-ALL) in recent decades, a notable portion of children still confronts challenges such as treatment resistance and recurrence, leading to limited options and a poor prognosis. LIM domain-binding protein 1 (LDB1) has been confirmed to exert a crucial role in various physiological and pathological processes. In our research, we aim to elucidate the underlying function and mechanisms of LDB1 within the background of T-ALL. Methods Employing short hairpin RNA (shRNA) techniques, we delineated the functional impact of LDB1 in T-ALL cell lines. Through the application of RNA-Seq, CUT&Tag, and immunoprecipitation assays, we scrutinized master transcription factors cooperating with LDB1 and identified downstream targets under LDB1 regulation. Results LDB1 emerges as a critical transcription factor co-activator in cell lines derived from T-ALL. It primarily collaborates with master transcription factors (ERG, ETV6, IRF1) to cooperatively regulate the transcription of downstream target genes. Both in vitro and in vivo experiments affirm the essential fuction of LDB1 in the proliferation and survival of cell lines derived from T-ALL, with MYB identified as a significant downstream target of LDB1. Conclusions To sum up, our research establishes the pivotal fuction of LDB1 in the tumorigenesis and progression of T-ALL cell lines. Mechanistic insights reveal that LDB1 cooperates with ERG, ETV6, and IRF1 to modulate the expression of downstream effector genes. Furthermore, LDB1 controls MYB through remote enhancer modulation, providing valuable mechanistic insights into its involvement in the progression of T-ALL.

Abstract Examining tumor-associated macrophages in the immune microenvironment of non-small cell lung cancer (NSCLC) is essential for gaining an understanding of the genesis and development of NSCLC as well as for identifying key clinical therapeutic targets. Although previous studies have reported the diverse phenotypes and functions of macrophages in tumor tissues, thereby highlighting their significant role in the tumor microenvironment, the characteristic differences and correlations between tumor and peritumor tissue-derived macrophages that are necessary for an understanding of NSCLC progression remain unclear. Based on single-cell RNA sequencing, we generated a comprehensive dataset of transcriptomes from NSCLC tumor and peritumor tissues, thereby facilitating comprehensive analysis and providing significant insights. In summary, our dataset will serve as a valuable transcriptomic resource for further studies investigating NSCLC development.

Abstract Background Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. Methods Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. Results HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease. Conclusion The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

Abstract Background With the increasing incidence of renal lesions, pretreatment differentiation between benign and malignant lesions is crucial for optimized management. This study aimed to develop a machine learning model utilizing radiomic features extracted from various regions of interest (ROIs), intratumoral ecological diversity features, and clinical factors to classify renal lesions. Methods CT images (arterial phase) of 1,795 renal lesions with confirmed pathology from three hospital sites were split into development (1184, 66%) and test (611, 34%) cohorts by surgery date. Conventional radiomic features were extracted from eight ROIs of arterial phase images. Intratumoral ecological diversity features were derived from intratumoral subregions. The combined model incorporating these features with clinical factors was developed, and its performance was compared with radiologists’ interpretation. Results Combining intratumoral and peritumoral radiomic features, along with ecological diversity features yielded the highest AUC of 0.929 among all combinations of features extracted from CT scans. After incorporating clinical factors into the features extracted from CT images, our combined model outperformed the interpretation of radiologists in the whole (AUC = 0.946 vs 0.823, P

AIM: To explore the DNA methylation of COL4A1 in ultraviolet-B (UVB)-induced age-related cataract (ARC) models in vitro and in vivo. METHODS: Human lens epithelium B3 (HLEB3) cells and Sprague Dawley rats were exposure to UVB respectively. The MTT assay was utilized to evaluate cell proliferation. Flow cytometry was employed for analysis of cell apoptosis and cell cycle. COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence. The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR (BSP). DNMTs and TETs mRNA levels was examined by RT-PCR. RESULTS: UVB exposure decreased HLEB3 cells proliferation, while increased the apoptosis rate and cells were arrested in G0/G1 phase. COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls. Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure. Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls, while expressions of TETs including TET1/2/3 showed the opposite trend. Results from the UVB treated rat model further confirmed the decreased expression of COL4A1, hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/ in UVB exposure group. CONCLUSION: DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

Gravelly soil strata exhibit heterogeneity and nonlinearity in their physical and mechanical properties, leading to volatile fluctuations of shield scraper force. Understanding the performance of shield scrapers in gravelly soils is significant for the safe and efficient excavation of tunnel boring machines. This paper conducts unconsolidated-undrained triaxial tests to obtain the mechanical properties of gravelly soils with gravel content ranging from 0 % to 30 %. The process of shield scrapers cutting through gravelly soils is analyzed by combining the varying mechanical properties of gravelly soils with the limit equilibrium analysis method. Subsequently, modified models for predicting the scraper force and specific energy in gravelly soils are established. Based on these models, the impact of key factors on the scraper performance is analyzed. Laboratory experiments are further performed on a rotary test bench to validate these models. The experimental results demonstrate that the horizontal cutting force and specific energy of shield scrapers in gravelly soils can be predicted with mean average errors of 8.8 % and 7.3 %, respectively, with the errors of all predicted values falling within ±20 % of the experimental results. These established models can serve as useful references for the structural and operational design of shield scrapers in gravelly soil strata.

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl2-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O2 generated by CaO2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro, as well as angiogenesis and osteogenic differentiation with the assistance of Zn2+. More significantly, the synergy of O2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.

Dielectric ceramics with low permittivity (εr), high quality factor (Q×f), and near-zero resonant frequency (τf) in the microwave bands are key materials used in fifth/sixth-generation (5G/6G) telecommunication, whileτf of most low-εr microwave dielectric ceramics is relatively negative. In this work, the first low-εr Ga-based ceramic SrGa12O19 with an anomalous positive τf was reported, and the causes of the positive τf, intrinsic polarization, and loss mechanism were systematically studied. X-ray diffraction (XRD) and transmission electron microscopy (TEM) revealed that the SrGa12O19 ceramic formed a pure hexagonal magnetoplumbite structure with spinel blocks and rock-salt blocks stacked along the crystallographic c-axis. When sintered at 1430 °C, it possessed the optimal microwave dielectric properties of a low εr of 14.46, high Q×f of 64,705 GHz, and exceptional positive τf of +55.7 ppm/°C, along with a low linear thermal expansion coefficient (αL) of 11.617 ppm/°C. The large positive deviation between εr and εr(C–M) of 45.31% resulted from the rattling effect of atoms in the rock-salt block. The unique positive τf (+55.7 ppm/°C) was governed by the rattling effect, resulting in a positive ταm (the temperature coefficient of ion polarizability) of 8.489 ppm/°C and a large negative temperature coefficient of permittivity (τε) of −132.864 ppm/°C. Phillips–Vechten–Levine (P–V–L) chemical bond theory revealed greater contributions of the spinel block to bond ionicity (fi, 52.95%), permittivity (ε, 55.15%), bond energy (E, 56.87%), and lattice energy (U, 74.88%) than those of the rock-salt block. The intrinsic dielectric properties were analyzed using infrared (IR) reflectivity spectra. The favorable performance of the SrGa12O19 ceramic indicated that it is a novel τf compensator. This selection of compounds with different structural layer combinations provides a new idea for exploring excellent microwave dielectric ceramics.

Abstract. From the early Taoist diagrams of the human body to the end of the Qing dynasty and the beginning of the Republic of China, Taoists exaggerated and deformed the human spine in a shape-shifting manner. It is likely that medical practitioners were influenced by this style of representation, and there are also numerous diagrams of the human body with the curved spine in the lateral-view diagrams of viscera and Ming Tang Tu (明堂图 Acupuncture and Moxibustion Chart), which constantly show the human torso in an elliptical “egg shape”. No later than the Ming dynasty, medical practitioners began to depict the actual physiological spinal curve of the human body. By the Qing dynasty, the depiction of the spinal curve in medical diagrams of the human figure showed a tendency to part ways with the Taoist freehand style of the previous generation. Although the representation of the curve of the spine was very crude, later medical images of the human body at least gradually straightened the spine and no longer depicted it in a shape-shifting manner. However, the curved spine in Taoist diagrams of the human body continued to exist, and the presentation of the curved spine never changed. This way of depicting its appearance, which is very different from reality, is shaped by Taoism’s special way of perceiving and viewing the body, and may also contain another form of truth.

Abstract Four-dimensional scanning transmission electron microscopy, coupled with a wide array of data analytics, has unveiled new insights into complex materials. Here, we introduce a straightforward unsupervised machine learning approach that entails dimensionality reduction and clustering with minimal hyperparameter tuning to semi-automatically identify unique coexisting structures in metallic alloys. Applying cepstral transformation to the original diffraction dataset improves this process by effectively isolating phase information from potential signal ambiguity caused by sample tilt and thickness variations, commonly observed in electron diffraction patterns. In a case study of a NiTiHfAl shape memory alloy, conventional scanning transmission electron microscopy imaging struggles to accurately identify a low-contrast precipitate at lower magnifications, posing challenges for microscale analyses. We find that our method efficiently separates multiple coherent structures while using objective means of determining hyperparameters. Furthermore, we demonstrate how the clustering result facilitates more robust strain mapping to provide immediate and quantitative structural insights.

Abstract Background Osteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach. Methods Annual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test. Results From 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8–6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P

Abstract Background Our aim was to evaluate the influence of staged goal directed therapy (GDT) on postoperative pulmonary complications (PPCs), intraoperative hemodynamics and oxygenation in patients undergoing Mckeown esophagectomy. Methods Patients were randomly divided into three groups, staged GDT group (group A, n = 56): stroke volume variation (SVV) was set at 8–10% during the one lung ventilation (OLV) stage and 8–12% during the two lung ventilation (TLV) stage, GDT group (group B, n = 56): received GDT with a target SVV of 8–12% During the entire surgical procedure, and control group (group C, n = 56): conventional fluid therapy was administered by mean arterial pressure (MAP), central venous pressure (CVP), and urine volume. The primary outcome was the incidence of postoperative pulmonary complications within Postoperative days (POD) 7. The secondary outcomes were postoperative lung ultrasound (LUS) B-lines artefacts (BLA) scoring, incidence of other complications, the length of hospital stay, intraoperative hemodynamic and oxygenation indicators included mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), cardiac output (CO), oxygenation index (OI), respiratory indices (RI), alveolar-arterial oxygen difference (Aa-DO2). Results Patients in group A and group B had a lower incidence of PPCs (7/56 vs. 17/56 and 9/56 vs. 17/56, p

Abstract Ultrafast lasers have become powerful tools in various fields, and increasing their fundamental repetition rates to the gigahertz (GHz) level holds great potential for frontier scientific and industrial applications. Among various schemes, passive mode-locking in ultrashort-cavity fiber laser is promising for generating GHz ultrashort pulses (typically solitons), for its simplicity and robustness. However, its pulse energy is far lower than the critical value of the existing theory, leading to open questions on the mode-locking mechanism of GHz fiber lasers. Here, we study the passive mode-locking in GHz fiber lasers by exploring dynamic gain depletion and recovery (GDR) effect, and establish a theoretical model for comprehensively understanding its low-threshold mode-locking mechanism with multi-GHz fundamental repetition rates. Specifically, the GDR effect yields an effective interaction force and thereby binds multi-GHz solitons to form a counterpart of soliton crystals. It is found that the resulting collective behavior of the solitons effectively reduces the saturation energy of the gain fiber and permits orders of magnitude lower pulse energy for continuous-wave mode-locking (CWML). A new concept of quasi-single soliton defined in a strongly correlated length is also proposed to gain insight into the dynamics of soliton assembling, which enables the crossover from the present mode-locking theory to the existing one. Specifically, two distinguishing dynamics of Q-switched mode-locking that respectively exhibit rectangular- and Gaussian-shape envelopes are theoretically indicated and experimentally verified in the mode-locked GHz fiber laser through the measurements using both the standard real-time oscilloscope and emerging time-lens magnification. Based on the proposed criterion of CWML, we finally implement a GDR-mediated mode-locked fiber laser with an unprecedentedly high fundamental repetition rate of up to 21 GHz and a signal-to-noise ratio of 85.9 dB.

Abstract Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation—a dynamic and reversible post-translational modification—on TRPV1’s function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS GC cells. By mutating amino acids near TRPV1’s existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse GC model. Further investigation reveals that TRPV1 SUMOylation increases the protein’s membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells.

Liver transplantation (LT) is the only effective treatment for hepatopulmonary syndrome (HPS). Moreover, perioperative refractory hypoxemia (pRH) is a prevalent life-threatening condition and has extremely limited treatment options. Here, we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies, ephedrine inhalation, intravenous use of methylene blue with nitric oxide (NO) inhalation, and NO inhalation alone. The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury. Early initiation of NO inhalation, rather than ephedrine, can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications. Therefore, based on the response to these exploratory salvage treatments, we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS. We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

Objective To construct a relationship model of emotional intelligence, psychological capital and professional identity by using structural equation model in probationer nursing students, explore the mechanism of interaction among them, and investigate the corresponding intervention measures in combination with the present situation of their emotional intelligence and psychological capital in order to improve their professional identity. Methods An anonymous survey was conducted on 308 probationer nursing students, with questionnaires including General Information Questionnaire, Wong and Law Emotional Intelligence Scale (WLEIS), and Psychological Capital Questionnaire (PCQ) and Professional Identity Questionnaire for Nurse Students (PIQNS). AMOS25.0 software was used to establish a structural equation model fitting the relationship of emotional intelligence, psychological capital and professional identity. Results There were positive correlations between each other among emotional intelligence, psychological capital and professional identity in the students (r=0.681~0.755, P

Abstract Background The induced membrane technique (IMT) is a two-step procedure used for reconstructing segmental bone defects in the limbs. The osteogenic mechanism after bone grafting using IMT remains unclear, and efforts to modify the original techniques are limited to the investigative phase. Therefore, reviewing existing knowledge and identifying hotspots and new trends in IMT is critical. Methods We retrieved reviews and articles associated with IMT published between 2004 and 2023 from the Web of Science Core Collection (WoSCC). The keywords included induced membrane technique, guided bone regeneration, bone defect reconstruction, bone graft, stem cells, Masquelet technique, management of bone defects, and scaffold. HistCite, VOSviewer, CiteSpace, and R-bibliometrics were used for scientometric analysis. Results A total of 1019 publications from 374 academic journals with 33,995 co-cited references by 2,331 institutions from 65 countries or regions were included. China (n = 235) and the United States (n = 215) were the most productive countries, with Shanghai Jiao Tong University producing the most number of publications (n = 18). Journal Injury [co-citations = 1774; impact factor (IF) 2022 = 2.5] published the most manuscripts, while Masquelet AC and Giannoudis PV published literature with a significant influence on IMT, showing more co-citations (n = 727; n = 355). Two preface hotspots of IMT focused on investigating the microscopic mechanism (such as the membrane supporting graft-to-bone union and the role of inflammatory cells) and developing new techniques to improve IMT (such as bone tissue engineering and new drugs). Conclusion This study comprehensively reviewed the literature about IMT published in the last 20 years using qualitative and quantitative methods, providing valuable information for researchers investigating IMT.

Abstract Background Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a prevalent condition that has been associated with various forms of cancer. Although some clinical studies suggest a potential link between OSA and lung cancer, this association remains uncertain, and the underlying mechanisms are not fully understood. This study investigated the role of the catecholamine-β-adrenergic receptor (βAR) and the NLRP3 inflammasome in mediating the effects of CIH on lung cancer progression in mice. Methods Male C57BL/6 N mice were subjected to CIH for four weeks, with Lewis lung carcinoma cells seeded subcutaneously. Propranolol (a βAR blocker) or nepicastat (an inhibitor of catecholamine production) was administered during this period. Tumor volume and tail artery blood pressure were monitored. Immunohistochemical staining and immunofluorescence staining were employed to assess protein expression of Ki-67, CD31, VEGFR2, PD-1, PD-L1, and ASC specks in tumor tissues. ELISA was used to detect catecholamine and various cytokines, while western blot assessed the expression of cyclin D1, caspase-1, and IL-1β. In vitro tube formation assay investigated angiogenesis. NLRP3 knockout mice were used to determine the mechanism of NLRP3 in CIH. Results CIH led to an increase in catecholamine. Catecholamine-βAR inhibitor drugs prevented the increase in blood pressure caused by CIH. Notably, the drugs inhibited CIH-induced murine lung tumor growth, and the expression of Ki-67, cyclin D1, CD31, VEGFR2, PD-1 and PD-L1 in tumor decreased. In vitro, propranolol inhibits tube formation induced by CIH mouse serum. Moreover, CIH led to an increase in TNF-α, IL-6, IL-1β, IFN-γ and sPD-L1 levels and a decrease in IL-10 in peripheral blood, accompanied by activation of NLRP3 inflammasomes in tumor, but these effects were also stopped by drugs. In NLRP3-knockout mice, CIH-induced upregulation of PD-1/PD-L1 in tumor was inhibited. Conclusions Our study underscores the significant contribution of β-adrenergic signaling and the NLRP3 inflammasome to CIH-induced lung cancer progression. These pathways represent potential therapeutic targets for mitigating the impact of OSA on lung cancer.

Abstract Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10–9) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research.

Abstract Background Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. Methods Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months’ ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. Results Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (P FWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (P FDR

Abstract Background Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. Methods This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. Results Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. Conclusion Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM.

INTRODUCTION: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged

Abstract Background Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood. Method Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The ‘oncoPredict’ algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2′-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients. Result Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ). Conclusion Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.