Search Results (205)

Cryotherapy could stimulate immune responses and induce abscopal effects. A novel technique was developed for treating spinal bone tumors involving the use of frozen tumor-containing autologous bone grafts for anterior spinal reconstruction following total en-bloc spondylectomy, with the aim of activating cryoimmunity. This study focused on analyzing changes in the T-cell receptor (TCR) repertoire after surgery to evaluate T-cell diversity. Blood samples were collected pre- and post-operatively, with subsequent RNA extraction and immunosequencing. Compared to pre-surgery samples, the diversity and abundance of the Complementarity-Determining Region 3, regions of the TCR α and β chains decreased, suggesting that more selective clones may have emerged and influenced immune responses. Through TCR repertoire analysis, this study demonstrated that transplantation of frozen tumor-containing autologous bone impacted the immune system. This study is expected to provide a foundation for developing treatments that may enhance immune activation. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Background: Esophageal squamous cell carcinoma (ESCC) is a fatal malignant tumor. Several studies have demonstrated that immune checkpoint inhibitors can provide clinical benefits to patients with ESCC. However, the single-agent efficacy of these agents remains limited. Although combination therapies (e.g., radiotherapy, chemotherapy) can help to overcome immunotherapy resistance in ESCC, their severe side effects limit clinical application. This study aimed to explore new resistance mechanisms to immunotherapy in ESCC and identify novel molecular targets to overcome immunotherapy resistance. Methods: We employed immunohistochemistry staining to examine the p-FGFR1^Y654 in tumor samples obtained from 103 patients with ESCC, in addition to evaluating CD8+ T cell infiltration. In vitro expression, western blotting, CCK-8, 5-bromo-2′-deoxyuridine incorporation assays, and migration assays were used to confirm the impact of AZD4547 on p-FGFR1^Y654 expression and the proliferation and migration in ESCC cell lines. Through RNA sequencing analysis, databases such as the Cancer Genome Atlas (TCGA) and Gene Set Cancer Analysis (GSCA), and the reconstruction of transgenic mice using the humanized immune system, we validated the correlation between the expression of p-FGFR1^Y654 and CD8+ T cell infiltration. We also explored how p-FGFR1^Y654 recruits myeloid-derived suppressor cells (MDSCs) through the CXCL8–CXCR2 axis to suppress the therapeutic efficacy of immunotherapy in ESCC. Finally, the tumor-suppressive effects of AZD4547 combined with immunotherapy were confirmed in vivo in tumor-bearing mice with a humanized immune system. Results: We found that the inhibition of p-FGFR1^Y654 expression in ESCC can enhance CD8+ T cell infiltration by suppressing the CXCL8-–XCR2 recruitment of MDSCs. AZD4547, combined with immunotherapy, further promotes immunotherapeutic efficacy in ESCC. Conclusions: In conclusion, our study presents a promising model for combination therapy in ESCC immunotherapy. Full article

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality despite advances in treatments, necessitating more effective therapeutic strategies. Single-cell RNA sequencing (scRNA-seq) technology has revolutionized our ability to dissect the cellular complexity of cancers, which is often obscured in conventional bulk transcriptomic experiments. Methods: In this study, we performed an integrative analysis of scRNA-seq data from multiple LUAD patient cohorts to investigate cell-type-specific transcriptomic changes across disease stages. Clustering, lineage trajectory analysis, and transcriptional regulatory network reconstruction were employed to identify stage-specific gene markers and their upstream regulators. Additionally, we constructed intercellular communication networks to evaluate signaling changes within the tumor microenvironment (TME) during LUAD progression. Results: Our analysis revealed that epithelial cells from stage IV tumors exhibited a distinct transcriptional profile compared to earlier stages, a separation not observed in immune or stromal cell populations. We identified a panel of gene markers that differentiated epithelial cells across disease stages and effectively stratified patients into subgroups with distinct survival outcomes and TME compositions. Regulatory network analysis uncovered key transcription factors, including ATF3, ATF4, HSF1, KLF4, and NFIC, as potential upstream regulators of these stage-specific genes. Moreover, cell–cell communication analysis revealed a significant increase in signaling originating from epithelial cells and a concomitant decrease in immune-derived signals in late-stage LUAD. We identified several signaling pathways enriched in stage-specific crosstalk, including Wnt, PTN, and PDGF pathways, which may play critical roles in LUAD progression. Conclusions: This study provides a comprehensive single-cell resolution map of LUAD progression, highlighting epithelial-driven regulatory programs and dynamic intercellular communication within the TME. Our findings uncover novel molecular markers and regulatory mechanisms with potential prognostic and therapeutic value for more precise treatment. Full article

Tracheal defects have been the focus of research since the 19th century, but reconstructing this complex structure remains challenging. Identifying a safe, effective tracheal substitute is a key goal of surgery. This integrative review explores current tracheal substitutes and tissue engineering techniques. Data were collected from June 2024 to March 2025 from electronically available databases. Articles published between 2015 and 2025 were selected using the individualized protocol for each database. After screening 190 articles, 82 were excluded, and 108 were reviewed, with 100 meeting the final inclusion criteria. Recent substitutes include three-dimensional synthetic grafts made from polycaprolactone and copolyamide with thermoplastic elastomer, thermoplastic polyurethane and polylactic acid. Additionally, models using decellularized and recellularized tracheal matrix scaffolds and bioprinting techniques are being developed. Comparative studies of synthetic grafts and tracheal scaffolds, as well as cell self-aggregation methods to create tracheal analogues, are discussed. Advances in hybrid approaches combining synthetic polymers with extracellular matrix components aim to improve biocompatibility and functional integration. The importance of selecting appropriate preclinical animal models, such as goats, is also highlighted for translational relevance. Further research is required to refine protocols, overcome challenges related to vascularization and immune response, and ensure the development of clinically viable, long-lasting tracheal substitutes. Full article

As the most basic mechanical components, bearing troubleshooting is essential to ensure the safe and reliable operation of rotating machinery. Bearing fault diagnosis is challenging due to the scarcity of bearing fault diagnosis samples and the susceptibility of fault signals to external noise. To address these issues, a ResNet-CACNN-BiGRU-SDPA bearing fault diagnosis method based on time–frequency bi-domain and feature fusion is proposed. First, the model takes the augmented time-domain signals as inputs and reconstructs them into frequency-domain signals using FFT, which gives the signals a bi-directional time–frequency domain receptive field. Second, the long sequence time-domain signal is processed by a ResNet residual block structure, and a CACNN method is proposed to realize local feature extraction of the frequency-domain signal. Then, the extracted time–frequency domain long sequence features are fed into a two-layer BiGRU for bidirectional deep global feature mining. Finally, the long-range feature dependencies are dynamically captured by SDPA, while the global dual-domain features are spliced and passed into Softmax to obtain the model output. In order to verify the model performance, experiments were carried out on the CWRU and JNU bearing datasets, and the results showed that the method had high accuracy under both small sample size and noise perturbation conditions, which verified the model’s good fault-feature-learning capability and noise immunity performance. Full article

Exercise metrics are critical for assessing health, but real-time heart rate and respiration measurements remain challenging. We propose a physiological monitoring system that uses an in-ear microphone to extract heart rate and respiration from faint ear canal signals. An improved non-negative matrix factorization (NMF) algorithm combines with a short-time Fourier transform (STFT) to separate physiological components, while an inverse Fourier transform (IFT) reconstructs the signal. The earplug effect enhances the low-frequency components, thereby improving the signal quality and noise immunity. Heart rate is derived from short-term energy and zero-crossing rate, while a BiLSTM-based model can refine the breathing phases and calculate indicators such as respiratory rate. Experiments have shown that the average accuracy can reach 91% under various conditions, exceeding 90% in different environments and under different weights, thus ensuring the system’s robustness. Full article

(1) Differential co-expression analysis between two phenotypes with a known gene set helps to uncover gene regulation alterations. (2) GSNCASCR uses CSCORE to estimate the gene pair correlations for network reconstruction and GSNCA to quantify the structure changes of co-expression networks of the predefined gene sets. It also ranks genes based on their “importance” in the weighted network. The method is implemented with free R software (version 0.1.0, available on GitHub), allowing users to analyze their data with the help of demo vignettes included in the package. (3) With analysis of both simulated and real datasets, we demonstrate that the statistical tests performed with GSNCASCR are able to identify differentially co-expressed gene sets with higher precision than tests with Gene Set Co-Expression Analysis (GSCA, version 1.1.1) and Gene Sets Net Correlations Analysis (GSNCA, version 1.42.0). Specifically, GSNCASCR achieved an AUC value of 0.985, while GSNCA and GSCA achieved 0.817 and 0.893, respectively, when positive and negative pathways are defined as having more than 40% and less than 20% co-expressed gene pairs in the simulated data, respectively. Furthermore, across simulated data with varying noise levels, pathway sizes, and positive/negative pathway definitions, GSNCASCR consistently performs best in over 90% of scenarios, as evaluated by AUC values. With an available COVID-19 dataset, we show CD4⁺ T cell dysfunction in severe COVID-19 as TNF-α/TNF receptor 1-dependent immune pathways. In the weighted network of a gene set of IFN-γ, IFITM3 was identified as a hub gene, which has been evidenced by a genome-wide association study and functional studies. (4) We developed a bioinformatics tool, GSNCASCR, that analyzes differentially co-expressed pathways with single-cell RNA-sequencing data and also evaluates the importance of the genes within pathways. This tool combines the advantages of two algorithms, enabling the quantification and examination of cell type-specific co-expression changes within pathways. The package allows for the analysis of shared and unique disease-affected pathways across different cell types. Full article

A star tracker is widely used as a high-precision attitude measurement device for spacecraft. It calculates attitude by extracting the magnitude and the position of presumed detected stars by a CCD/CMOS sensor and matching them with stars in the star catalog. The traditional star identification methods typically require the selection of specific anchor stars, which may cause insufficient identification accuracy as the number of stars used in the rough search is limited. In this paper, we propose a star identification method based on spatial projection, which starts with preprocessing. Then, a method for online expansion and reconstruction of the star catalog is proposed, which provides more stored star data. After the rough recognition and coordinate system transformation, the final identification is realized in the polar coordinate system. All the star points in the star image are identified, and the attitude information is obtained at the same time. The performance of the identification method is verified by real night sky experiments. Stray light experiments are also carried out to prove good noise immunity capabilities. Compared with the traditional subgraph isomorphism method, the proposed method makes it easier to adjust the number of recognizable stars in the field of view and better recognition of specific areas. The method is of great significance for future tasks such as attitude measurement, celestial navigation, remote sensing measurement, and space target observation and tracking. Full article

Novel view synthesis and 3D reconstruction have been extensively studied. Three-dimensional Gaussian Splatting (3DGS) has gained popularity due to its rapid training and real-time rendering capabilities. However, RGB imaging is highly dependent on ideal illumination conditions. In low-light situations such as at night or in the presence of occlusions, RGB images often suffer from blurred contours or even complete failure in imaging, which severely restricts the application of 3DGS in such scenarios. Thermal imaging technology, on the other hand, serves as an effective complement. Thermal images are solely influenced by heat sources and are immune to illumination conditions. This unique property enables them to clearly identify the contour information of objects in low-light environments. Nevertheless, thermal images exhibit significant limitations in presenting texture details due to their sensitivity to temperature variations rather than surface texture features. To capitalize on the strengths of both, we propose thermal geometrically accurate Gaussian Splatting (TGA-GS), a novel Gaussian Splatting model. TGA-GS is designed to leverage RGB and thermal information to generate high-quality meshes in low-light conditions. Meanwhile, given low-resolution thermal images and low-light RGB images as inputs, our method can generate high-resolution thermal and RGB images from novel viewpoints. Moreover, we also provide a real thermal imaging dataset captured with a handheld thermal infrared camera. This not only enriches the information content of the images but also provides a more reliable data basis for subsequent computer vision tasks in low-light scenarios. Full article

This study examines the jurisdictional disputes between the bishop of Malta and the grand masters of the Order of St John during the first half of the seventeenth century, specifically from 1563 to 1650, in the wake of the Council of Trent. It focuses on conflicts concerning ecclesiastical immunities—personal, real (material), and local—as key points of tension between spiritual and temporal authority in early modern Malta. By analysing extensive archival correspondence preserved in the diocesan archive of Malta between the bishop, the grand master, and the Holy See, the study reconstructs how these immunities were invoked, negotiated, and contested. It employs a historical–legal methodology, interpreting these documents within the wider European context of Tridentine reform and absolutist State building. While established scholarship has highlighted broader patterns of Church–State conflict in early modern Europe, this study contributes an original case from the periphery of Catholic Christendom, where both bishop and grand master were ultimately subject to the papacy. The article is structured around the three traditional forms of ecclesiastical immunity, each examined as a distinct yet interconnected site of struggle. It argues that, in Malta, the application of Tridentine reforms served both to consolidate episcopal authority and to provoke resistance from secular powers, revealing the complex, mediated nature of ecclesiastical governance. The study ultimately sheds light on how canonical tradition, papal intervention, and local political configurations shaped the contested boundaries of sacred and secular jurisdiction. Full article

Neutrophils are the most abundant type of immune cells and also the most underestimated cell defenders in the human body. In fact, their lifespan has also been extensively revised in recent years, going from a half-life of 8–10 h to a longer lifespan of up to 5.4 days in humans; it has been discovered that their mechanisms of defense are multiple and finely modulated, and it has been suggested that the heterogeneity of neutrophils occurs as well as in other immune cells. Neutrophils also play a critical role in the wound healing process, and their involvement is not limited to the initial stages of defense against pathogens, but extends to the inflammatory phase of tissue reconstruction. Neutrophil heterogeneity has recently been reported at the presence of distinct subtypes expressing different functional states, which contribute uniquely to the different phases of innate immunity and wound healing. This heterogeneity can be induced by the local microenvironment, by the presence of specific cytokines and by the type of injury. The different functional states of neutrophils enable a finely tuned response to injury and stress, which is essential for effective healing. Understanding the functional heterogeneity of neutrophils in wound healing can unveil potential pathological profiles and therapeutic targets. Moreover, the understanding of neutrophil heterogeneity dynamics could help in designing strategies to manage excessive inflammation or impaired healing processes. This review highlights the complexity of neutrophil heterogeneity and its critical roles throughout the phases of wound healing. Full article

In this paper, we adopt artificial intelligence (AI) technology for the electromagnetic imaging of uniaxial objects buried in a half-space environment. The limited measurement angle inherent to half-space configurations significantly increases the difficulty of data collection. This paper discusses the simultaneous emission of Transverse Magnetic (TM) and Transverse Electric (TE) electromagnetic waves to illuminate a uniaxial object embedded in a half-space. The dominant current scheme (DCS) and the backpropagation scheme (BPS) are subsequently employed to compute the initial permittivity distribution, which is then used as a dataset for training Convolutional Neural Networks (CNNs). The numerical results compare the reconstruction capabilities of both methods under identical conditions, demonstrating that the DCS exhibits superior generalization and noise immunity compared to the BPS. These findings confirm the effectiveness of both schemes in reconstructing the dielectric constant distribution of uniaxial objects buried in a half-space. Full article

The evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution and viral adaptation. This study investigates the structural and evolutionary dynamics of the double-domain restriction factors A3F and A3G and their viral inhibitor, Vif, across diverse primate species. By constructing 3D structural homology models and integrating ancestral sequence reconstruction (ASR), we identified patterns of sequence diversity, structural conservation, and functional adaptation. Inactive CD1 (Catalytic Domain 1) domains displayed greater sequence diversity and more positive surface charges than active CD2 domains, aiding nucleotide chain binding and intersegmental transfer. Despite variability, the CD2 DNA-binding grooves remained structurally consistent with conserved residues maintaining critical functions. A3F and A3G diverged in loop 7’ interaction strategies, utilising distinct molecular interactions to facilitate their roles. Vif exhibited charge variation linked to host species, reflecting its coevolution with A3 proteins. These findings illuminate how structural adaptations and charge dynamics enable both restriction factors and their viral antagonists to adapt to selective pressures. Our results emphasize the importance of studying structural evolution in host–virus interactions, with implications for understanding immune defense mechanisms, zoonotic risks, and viral evolution. This work establishes a foundation for further exploration of restriction factor diversity and coevolution across species. Full article

Vitellogenesis in fish represents a critical phase of oogenesis, significantly influencing the nutritional provisioning for oocyte maturation and subsequent offspring development. However, research on the physiological mechanisms governing vitellogenesis at the single-cell level remains limited. In this study, we performed single-nucleus RNA sequencing (snRNA-seq) on the ovaries of Sichuan bream (Sinibrama taeniatus). We first identified six distinct cell types (germ cells, follicular cells, immune cells, stromal cells, endothelial cells, and epithelial cells) in the ovaries based on typical functional marker genes. Subsequently, we reconstructed the developmental trajectory of germ cells using pseudotime analysis, which describes the transcriptional dynamics of germ cells at various developmental stages. Additionally, we identified transcription factors (TFs) specific to germ cells that exhibit high activity at each developmental stage. Furthermore, we analyzed the genetic functional heterogeneity of germ cells and follicular cells at different developmental stages to elucidate their contributions to vitellogenesis. Finally, cell interaction analysis revealed that germ cells communicate with somatic cells or with each other via multiple receptors and ligands to regulate growth, development, and yolk acquisition. These findings enhance our understanding of the physiological mechanisms underlying vitellogenesis in fish, providing a theoretical foundation for regulating ovarian development in farmed fish. Full article