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Abstract Background Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. Methods We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. Results lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. Conclusion This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.

Abstract Background Type 2 diabetes mellitus (T2DM), characterized by β-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. Methods WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. Results Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic β-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs. Conclusion Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs.

Gastric cancer, the fifth most prevalent cancer worldwide, is often diagnosed in advanced stages with limited treatment options. Examining the tumor microenvironment (TME) and its metabolic reprogramming can provide insights for better diagnosis and treatment. This study investigates the link between TME factors and metabolic activity in gastric cancer using bulk and single-cell RNA-sequencing data. We identified two molecular subtypes in gastric cancer by analyzing the distinct expression patterns of 81 prognostic genes related to the TME and metabolism, which exhibited significant protein-level interactions. The high-risk subtype had increased stromal content, fibroblast and M2 macrophage infiltration, elevated glycosaminoglycans/glycosphingolipids biosynthesis, and fat metabolism, along with advanced clinicopathological features. It also exhibited low mutation rates and microsatellite instability, associating it with the mesenchymal phenotype. In contrast, the low-risk group showed higher tumor content and upregulated protein and sugar metabolism. We identified a 15-gene prognostic signature representing these characteristics, including CPVL, KYNU, CD36, and GPX3, strongly correlated with M2 macrophages, validated through single-cell analysis and an internal cohort. Despite resistance to immunotherapy, the high-risk group showed sensitivity to molecular targeted agents directed at IGF-1R (BMS-754807) and the PI3K-mTOR pathways (AZD8186, AZD8055). We experimentally validated these promising drugs for their inhibitory effects on MKN45 and MKN28 gastric cells. This study unveils the intricate interplay between TME and metabolic pathways in gastric cancer, offering potential for enhanced diagnosis, patient stratification, and personalized treatment. Understanding molecular features in each subtype enriches our comprehension of gastric cancer heterogeneity and potential therapeutic targets.

Herein, a novel strategy for regulating the phase structure was used to significantly enhance the recoverable energy storage density (Wrec) and the thermal stability via designing the (1-x)[(Bi0.5Na0.5)0.7Sr0.3TiO3]-xBiScO3 ((1-x)BNST-xBS) relaxor ferroelectric ceramics. The incorporation of BS into BNST ceramics markedly increases the local micro-structure disorder, causing a high polarization and inhibiting polarization hysteresis for 0.95BNST-0.05BS ceramics, leading to a large Wrec of 5.41 J/cm3 with an ideal efficiency (η) of 78.5%. Meanwhile, transmission electron microscope (TEM) results further proved that the nano-domain structure and the tetragonal (P4bm) phase superlattice structure of 0.95BNST-0.05BS ceramics possess an excellent thermal stability (20–200 °C). An outstanding Wrec value of 3.18 × (1.00 ± 0.03) J/cm3 and an η value of 74.500 ± 0.025 are achieved under a temperature range from 20 °C to 200 °C. This work provides a promising method for phase-structure design that can make it possible to apply temperature-insensitive ceramic dielectrics with a high energy storage density in harsh environments.

The multi-step magnetization behavior caused by a variety of microstructures is common in magnetic materials. The study of the effect of heterogeneous structure magnetization behavior on magnetic viscosity provides extensive guidance for the long-term stability of magnetic materials. The microstructure of Fe–Co–Ni–Al–Ti–Cu alloy was regulated by heat treatment process, and homogeneous structure (S810) and heterogeneous structure (S830) samples were prepared. In the S830 sample, there are three steps of magnetization reversal due to the presence of α1′ phases (split α1 phases). Part of the α1′ phases are reversed under a lower magnetic field, and the other part has strong interaction with the α1 phases forming a closed stable magnetic domain structure, which enhances the switch field of α1 phases. Both first-order reversal curves (FORC) analysis and electron holography have confirmed this phenomenon. The magnetic viscosity coefficient of S830 is higher, but its magnetic field dependence is better. The quantitative calculation of energy barriers shows that the energy barriers of α1′ phases are lower, which leads to the instability of S830 sample under low magnetic fields. The superposition of three magnetization reversal steps makes the variation of magnetic viscosity coefficient gentler.

Cystic echinococcosis (CE) is a worldwide neglected zoonotic disease caused by infection with the larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.), which predominantly resides in the liver accompanied by mild inflammation. Macrophages constitute the main cellular component of the liver and play a central role in controlling the progression of inflammation and liver fibrosis. However, the role of hepatic macrophages in the establishment and growth of hydatid cysts in the liver during E. granulosus sensu stricto (E. granulosus s.s.) infection has not been fully elucidated. Here, we showed that CD68+ macrophages accumulated in pericystic areas of the liver and that the expression of CD163, a marker of anti-inflammatory macrophages, was more evident in active CE patients than in inactive CE patients. Moreover, in a mouse model of E. granulosus s.s. infection, the pool of hepatic macrophages expanded dramatically through the attraction of massive amounts of monocyte-derived macrophages (MoMFs) to the infection site. These infiltrating macrophages preferentially polarized toward an iNOS+ proinflammatory phenotype at the early stage and then toward a CD206+ anti-inflammatory phenotype at the late stage. Notably, the resident Kupffer cells (KCs) predominantly maintained an anti-inflammatory phenotype to favor persistent E. granulosus s.s. infection. In addition, depletion of hepatic macrophages promoted E. granulosus s.s. larval establishment and growth partially by inhibiting CD4+ T-cell recruitment and liver fibrosis. The above findings demonstrated that hepatic macrophages play a vital role in the progression of CE, contributing to a better understanding of the local inflammatory responses surrounding hydatid cysts and possibly facilitating the design of novel therapeutic approaches for CE.

The TiB2/7075Al composites with various particle contents were fabricated through hot-pressing sintering and hot extrusion, and the influence of TiB2 particles on the mechanical properties and corrosion resistance were focused. The results indicated that the grain size was gradually refined and the texture strength was reduced with increasing the TiB2 content due to the greater deformation and recrystallization degrees in the matrix around particles. A high TiB2 content caused a reduction of friction coefficient and an improvement of wear resistance, and the fatigue wear transformed into abrasive wear. Since TiB2 particles hindered the corrosion channels and crack propagation of the composite, the resistances on intergranular and exfoliation corrosion were enhanced by the particles. However, the pitting corrosion was aggravated because the integrity of oxide film on the composite surface was destroyed by the particles. Although the composite exhibits lower electrochemical corrosion resistance than 7075Al without particle, while it could be improved again with increasing the TiB2 content.

The cestode Echinococcus multilocularis, which mainly dwells in the liver, leads to a serious parasitic liver disease called alveolar echinococcosis (AE). Despite the increased attention drawn to the immunosuppressive microenvironment formed by hepatic AE tissue, the immunological characteristics of hepatic dendritic cells (DCs) in the AE liver microenvironment have not been fully elucidated. Here, we profiled the immunophenotypic characteristics of hepatic DC subsets in both clinical AE patients and a mouse model. Single-cell RNA sequencing (scRNA-Seq) analysis of four AE patient specimens revealed that greater DC numbers were present within perilesional liver tissues and that the distributions of cDC and pDC subsets in the liver and periphery were different. cDCs highly expressed the costimulatory molecule CD86, the immune checkpoint molecule CD244, LAG3, CTLA4, and the checkpoint ligand CD48, while pDCs expressed these genes at low frequencies. Flow cytometric analysis of hepatic DC subsets in an E. multilocularis infection mouse model demonstrated that the number of cDCs significantly increased after parasite infection, and a tolerogenic phenotype characterized by a decrease in CD40 and CD80 expression levels was observed at an early stage, whereas an activated phenotype characterized by an increase in CD86 expression levels was observed at a late stage. Moreover, the expression profiles of major immune checkpoint molecules (CD244 and LAG3) and ligands (CD48) on hepatic DC subsets in a mouse model exhibited the same pattern as those in AE patients. Notably, the cDC and pDC subsets in the E. multilocularis infection group exhibited higher expression levels of PD-L1 and CD155 than those in the control group, suggesting the potential of these subsets to impair T cell function. These findings may provide valuable information for investigating the role of hepatic DC subsets in the AE microenvironment and guiding DC targeting treatments for AE.

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. Whereas YAP inhibition enhanced the expression of cell-cell adhesions in VEC and affected valve shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism.

The larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.) caused a chronic infection, known as cystic echinococcosis (CE), which is a worldwide public health problem. The human secondary CE is caused by the dissemination of protoscoleces (PSCs) when fertile cysts are accidentally ruptured, followed by development of PSCs into new metacestodes. The local immune mechanisms responsible for the establishment and established phases after infection with E. granulosus s.l. are not clear. Here, we showed that T cells were involved in the formation of the immune environment in the liver in CE patients and Echinococcus granulosus sensu strict (E. granulosus s.s.)-infected mice, with CD4+ T cells being the dominant immune cells; this process was closely associated with cyst viability and establishment. Local T2-type responses in the liver were permissive for early infection establishment by E. granulosus s.s. between 4 and 6 weeks in the experimental model. CD4+ T-cell deficiency promoted PSC development into cysts in the liver in E. granulosus s.s.-infected mice. In addition, CD4+ T-cell-mediated cellular immune responses and IL-10-producing CD8+ T cells play a critical role in the establishment phase of secondary E. granulosus s.s. PSC infection. These data contribute to the understanding of local immune responses to CE and the design of new therapies by restoring effective immune responses and blocking evasion mechanisms during the establishment phase of infection.

In the original publication [1], there were mistakes in the order of the references, which were as follows: [...]

Percolating composites with negative permittivity can be promising candidates for metamaterials. Herein, novel all-organic composite films containing of random coil polypyrrole (PPy) and poly(vinylidene fluoride) (PVDF) are fabricated via a solution casting method. The random coil PPy is prepared by oxidative template assembly approach for the first time. The experimental result indicates that the negative permittivity is easily adjusted through controlling the random coil PPy contents. Especially, the random coil PPy contents exceeded 7 wt% the negative permittivity appear attributed to the formation of 3D interconnected PPy network. This facile approach not only opens a new way to preparing negative permittivity of all-organic composite films, but also points out a route to facilitate the practical applications of metamaterials. Keywords: Polypyrrole, Composite films, Random coil, Negative permittivity

Horns, also known as headgear, are a unique structure of ruminants. As ruminants are globally distributed, the study of horn formation is critical not only for increasing our understanding of natural and sexual selection but also for the breeding of polled sheep breeds to facilitate modern sheep farming. Despite this, a significant number of the underlying genetic pathways in sheep horn remain unclear. In this study, to clarify the gene expression profile of horn buds and investigate the key genes in horn bud formation, RNA-sequencing (RNA-seq) technology was utilized to investigate differential gene expression in the horn buds and adjacent forehead skin of Altay sheep fetuses. There were only 68 differentially expressed genes (DEGs) identified, consisting of 58 up-regulated genes and 10 down-regulated genes. RXFP2 was differentially up-regulated in the horn buds and had the highest significance (p-value = 7.42 × 10−14). In addition, 32 DEGs were horn-related genes identified in previous studies, such as RXFP2, FOXL2, SFRP4, SFRP2, KRT1, KRT10, WNT7B, and WNT3. Further, Gene Ontology (GO) analysis showed that the DEGs were mainly enriched with regard to growth, development, and cell differentiation. Pathway analysis revealed that the Wnt signaling pathway may be responsible for horn development. Further, through combining the protein–protein interaction networks of the DEGs, it was found that the top five hub genes, namely, ACAN, SFRP2, SFRP4, WNT3, and WNT7B, were also associated with horn development. Our results suggest that only a few key genes, including RXFP2, are involved in bud formation. This study not only validates the expression of candidate genes identified at the transcriptome level in previous studies but also provides new possible marker genes for horn development, which may promote our understanding of the genetic mechanisms of horn formation.

Recently, the event camera has become a popular and promising vision sensor in the research of simultaneous localization and mapping and computer vision owing to its advantages: low latency, high dynamic range, and high temporal resolution. As a basic part of the feature-based SLAM system, the feature tracking method using event cameras is still an open question. In this article, we present a novel asynchronous event feature generation and tracking algorithm operating directly on event-streams to fully utilize the natural asynchronism of event cameras. The proposed algorithm consists of an event-corner detection unit, a descriptor construction unit, and an event feature tracking unit. The event-corner detection unit addresses a fast and asynchronous corner detector to extract event-corners from event-streams. For the descriptor construction unit, we propose a novel asynchronous gradient descriptor inspired by the scale-invariant feature transform descriptor, which helps to achieve quantitative measurement of similarity between event feature pairs. The construction of the gradient descriptor can be decomposed into three stages: speed-invariant time surface maintenance and extraction, principal orientation calculation, and descriptor generation. The event feature tracking unit combines the constructed gradient descriptor and an event feature matching method to achieve asynchronous feature tracking. We implement the proposed algorithm in C++ and evaluate it on a public event dataset. The experimental results show that our proposed method achieves improvement in terms of tracking accuracy and real-time performance when compared with the state-of-the-art asynchronous event-corner tracker and with no compromise on the feature tracking lifetime.

In this work, we reported the fabrication of different sizes of polystyrene colloidal arrays which were used as a template to fabricate large area gold nanocaps (AuNCs) and gold nanobowls (AuNBs) through sputter deposition and solvent etching. The monolayer self-assembly process, formation mechanism of surface-enhanced Raman scattering (SERS)-active structures, and characteristics of the SERS substrate were thoroughly studied and evaluated. Rhodamine 6G (R6G) was used as the target molecule to systematically compare the SERS signal changes with different substrate coatings. The AgNPs–AuNCs substrate in which Ag nanoparticles (AgNPs) were coated on the convex surface of AuNCs showed stronger and better-resolved spectra for the R6G molecule, and the limit of detection (LOD) of R6G reached as low as 10−7 M and its SERS enhancement factor (EF) approached 4.05 × 108. These results demonstrate that the prepared substrate has promising potential as a cost-effective, robust, and rapid detection tool for SERS-based trace detection. [ABSTRACT FROM AUTHOR]