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Fibrosis is a pathological feature of a variety of chronic inflammatory diseases that can affect almost all organs, which can cause severe consequences and even lead to death. Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) due to disruption of the balance between ECM production and degradation. Although overabundance of ECM proteins has long been the focus of studies on fibrosis, another facet of the problem—impaired degradation of the ECM—is gaining increasing attention. Matrix metalloproteinase (MMP) and the tissue inhibitor of metalloproteinase (TIMP) system is the main molecular system contributing to ECM degradation, and macrophages are the major regulators of ECM. However, the relationship among macrophages, the MMP/TIMP system and the ECM is not fully understood in the context of fibrosis. Here, we discuss in detail the role played by the ECM in the development of fibrosis and highlight the macrophage-MMP-ECM interaction that is involved in fibrogenesis and may be a potential therapeutic target for fibrosis.

Abstract B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

Abstract Leukocyte immunoglobulin-like receptor (LILR) B4 (also known as ILT3/CD85k) is an immune checkpoint protein that is highly expressed in solid tumors and hematological malignancies and plays a significant role in the pathophysiology of cancer. LILRB4 is highly expressed in acute myeloid leukemia (AML), and this phenotype is associated with adverse patient outcomes. Its differential expression in tumors compared to normal tissues, its presence in tumor stem cells, and its multifaceted roles in tumorigenesis position it as a promising therapeutic target in AML. Currently, several immunotherapies targeting LILRB4 are undergoing clinical trials. This review summarizes advancements made in the study of LILRB4 in AML, focusing on its structure, ligands, expression, and significance in normal tissues and AML; its protumorigenic effects and mechanisms in AML; and the application of LILRB4-targeted therapies in AML. These insights highlight the potential advantages of LILRB4 as an immunotherapeutic target in the context of AML.

The PEST-containing nuclear protein (PCNP) has been reported to play paradoxical roles in tumorigenesis. While PCNP functions as a tumor suppressor in neuroblastoma and lung adenocarcinoma, it has been identified as a tumor promoter in ovarian cancer. However, the underlying mechanisms driving these contrasting effects remain unclear. Gene Expression Profiling Interactive Analysis (GEPIA) was employed to analyze relevance of PCNP expression with prognosis in HCC. To evaluate the role of PCNP in hepatocellular carcinoma (HCC), we analyzed the expression of PCNP in 87 HCC tissues and 80 adjacent normal tissues. Correlation between PCNP and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was transcriptionally detected, and then their effects on malignant behaviors, including proliferation, invasion, tumor formation in vitro and in vivo were evaluated. According to tissues array results, it is found that PCNP was significantly upregulated in HCC tissues, which was further confirmed in HCC cell lines by western blotting. Importantly, both the cytoplasmic and nuclear PCNP fractions were correlated with pathological grade, T staging, clinical staging and recurrence, and patients with a high level of PCNP had lower overall survival and disease-free survival and a higher recurrence rate than those with a low PCNP level, indicating that PCNP might be an independent prognostic factor for HCC patients. Functional investigations revealed that PCNP knockdown inhibited malignant behaviors, including proliferation, invasion, colony formation and tumor formation, in vitro and in vivo. Pearson correlation analysis indicated a positive association between PCNP and UHRF2, with evidence that PCNP transcriptionally upregulates UHRF2. Furthermore, ectopic overexpression of PCNP activated the ErbB3/Ras/Raf1 signaling pathway through upregulation of UHRF2. Our findings suggest that PCNP promotes HCC progression by activating the ErbB3/Ras/Raf signaling pathway through upregulation of UHRF2. Consequently, PCNP holds potential as both a diagnostic biomarker and a therapeutic target for hepatocellular carcinoma.

Image encryption is an effective way to protect image data. However, existing image encryption algorithms are still unable to strike a good balance between security and efficiency. To overcome the shortcomings of these algorithms, an image encryption algorithm based on plane-level image filtering and discrete logarithmic transformation (IEA-IF-DLT) is proposed. By utilizing the hash value more rationally, our proposed IEA-IF-DLT avoids the overhead caused by repeated generations of chaotic sequences and further improves the encryption efficiency through plane-level and three-dimensional (3D) encryption operations. Aiming at the problem that common modular addition and XOR operations are subject to differential attacks, IEA-IF-DLT additionally includes discrete logarithmic transformation to boost security. In IEA-IF-DLT, the plain image is first transformed into a 3D image, and then three rounds of plane-level permutation, plane-level pixel filtering, and 3D chaotic image superposition are performed. Next, after a discrete logarithmic transformation, a random pixel swapping is conducted to obtain the cipher image. To demonstrate the superiority of IEA-IF-DLT, we compared it with some state-of-the-art algorithms. The test and analysis results show that IEA-IF-DLT not only has better security performance, but also exhibits significant efficiency advantages.

Fluids sampled from the gastrointestinal (GI) tract are of interest for evaluating the bioequivalence of oral medications, and more generally for evaluating GI-related diseases, and for profiling the individual gut microbiome. Existing options for capturing multiple fluid samples from specific locations in the GI tract are limited and invasive, particularly for the small intestine. Here, we report the development of an ingestible capsule for the collection of multiple fluid samples along the GI tract; we additionally report the use of data from sensors within the capsule to determine the sampling regions. The capsule has an ingestible size of Φ14 × 42 mm 3 . Within this volume, it includes three separate cartridges that capture and retain samples within capillaries; a stepper motor for positioning the sampling cartridges at a sampling port; a 3-axis accelerometer that enables a new method of correlating sample location; a microcontroller with wireless communication and sensor data storage capabilities; and batteries to power the device. We describe in vitro characterization and in vivo tests performed with canine models that have successfully verified the capabilities of the capsule. Fluid samples from the stomach, small intestine, and colon regions of the GI tract are identified by inertial measurements taken within the capsule, and correlated to measurements of the concentration of mesalamine (a drug used for testing) and the bile salt profile in each region, respectively.

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool “sigminer” has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.

Large area and highly aligned polymer semiconductor sub-microwires were fabricated using the coaxial focused electrohydrodynamic jet printing technology. As indicated by the results, the sub-microwire arrays have smooth morphology, well reproducibility and controllable with a width of ~110 nm. Analysis shows that the molecular chains inside the sub-microwires mainly exhibited edge-on arrangement and the π-stacking direction (010) of the majority of crystals is parallel to the long axis of the sub-microwires. Sub-microwires based organic field effect transistors showed high mobility with an average of 1.9 cm 2 V −1 s −1 , approximately 5 times higher than that of thin film based organic field effect transistors. In addition, the number of sub-microwires can be conveniently controlled by the printing technique, which can subsequently concisely control the performance of organic field effect transistors. This work demonstrates that sub-microwires fabricated by the coaxial focused electrohydrodynamic jet printing technology create an alternative path for the applications of high-performance organic flexible device. Here, the authors fabricate large area and highly aligned polymer semiconductor sub-microwires arrays via coaxial focused electrohydrodynamic jet printing technology, achieving high on/off ratio and average mobility that is 5x higher than that of thin film based organic field effect transistors.

Chaos-based encryption is promising for safeguarding digital images. Nonetheless, existing chaos-based encryption algorithms still exhibit certain shortcomings. Given this, we propose a novel multi-channel image encryption algorithm that leverages pixel reorganization and hyperchaotic maps (MIEA-PRHM). Our MIEA-PRHM algorithm employs two hyperchaotic maps to jointly generate chaotic sequences, ensuring a larger key space and better randomness. During the encryption process, we first convert input images into two fused matrices through pixel reorganization. Then, we apply two rounds of scrambling and diffusion operations, coupled with one round of substitution operations, to the high 4-bit matrix. For the low 4-bit matrix, we conduct one round of substitution and diffusion operations. Extensive experiments and comparisons demonstrate that MIEA-PRHM outperforms many recent encryption algorithms in various aspects, especially in encryption efficiency.

[2] Based on previous studies, immune dysregulation plays an important role in AML relapse, and immune-related genes may provide prognostic information for AML patients. [...]exploring the immune-related genetic prognostic index (IRGPI) to predict prognosis and therefore provide personalized guidance for ICI therapy is urgently needed. [3] Our results showed that the IRGPI-high group had a higher TIDE score than the IRGPI-low subgroup [Figure 1A], suggesting that IRGPI-low patients may benefit more from ICI therapy than IRGPI-high patients. [...]previous studies have shown that a higher TIDE prediction score is associated with a worse outcome. [4] However, both TIDE and TIS focus on the immune function of T cells. Since the composition of immune cell subtypes and expression of immunosuppressive molecules were different between the two IRGPI subgroups, the IRGPI might reflect different immune benefits from ICR therapy identified with TIDE. [...]the IRGPI is a promising immune-related prognostic biomarker that may help in distinguishing immune and molecular characteristics and predicting AML patient clinical outcomes. [...]as we only considered an index of immune-related genes, many prominent prognostic genes in AML might have been excluded. [...]it should be emphasized that the association between the risk score and immune activity has not yet been experimentally addressed.