Adhesive Interactions Research Articles

SAGA1 and MITH1 produce matrix-traversing membranes in the CO2-fixing pyrenoid.

Approximately one-third of global CO2 assimilation is performed by the pyrenoid, a liquid-like organelle found in most algae and some plants. Specialized pyrenoid-traversing membranes are hypothesized to drive CO2 assimilation in the pyrenoid by delivering concentrated CO2, but how these membranes are made to traverse the pyrenoid matrix remains unknown. Here we show that proteins SAGA1 and MITH1 cause membranes to traverse the pyrenoid matrix in the model alga Chlamydomonas reinhardtii. Mutants deficient in SAGA1 or MITH1 lack matrix-traversing membranes and exhibit growth defects under CO2-limiting conditions. Expression of SAGA1 and MITH1 together in a heterologous system, the model plant Arabidopsis thaliana, produces matrix-traversing membranes. Both proteins localize to matrix-traversing membranes. SAGA1 binds to the major matrix component, Rubisco, and is necessary to initiate matrix-traversing membranes. MITH1 binds to SAGA1 and is necessary for extension of membranes through the matrix. Our data suggest that SAGA1 and MITH1 cause membranes to traverse the matrix by creating an adhesive interaction between the membrane and matrix. Our study identifies and characterizes key factors in the biogenesis of pyrenoid matrix-traversing membranes, demonstrates the importance of these membranes to pyrenoid function and marks a key milestone toward pyrenoid engineering into crops for improving yields.

Clotting promotes glioma growth and infiltration through activation of focal adhesion kinase.

The tumor architecture of high-grade gliomas is shaped by tumor cell necrosis, invasive growth and the leakage of a fibrin-rich edema from poorly organized tumor blood vessels. Here, we demonstrate a marked upregulation of clot formation in the interstitial spaces of tumor tissues from patients with glioblastoma while tumor-free brain is essentially devoid of fibrin. The accumulation of fibrin in tumor interstitial spaces is functionally relevant as we demonstrate increased infiltration and growth of primary glioblastoma cells after embedding in a 3-dimensional matrix made of fibrin ex vivo. Additionally, we detected accelerated tumor growth after implanting glioblastoma cells together with clotted plasma in brains of immune deficient mice while glioblastoma development in clotting-deficient hemophilia mice was delayed. Glioblastoma growth correlated with the outgrowth of invadopodia and their adhesive interactions with the 3-dimensional clot matrix, which was mediated by integrins β1 and β3 and their common downstream target focal adhesion kinase (FAK). Knocking down FAK with CRISPR Cas9 caused an upregulation of p21/p27 cell cycle inhibitors, strong growth inhibition in cultured glioblastoma cells and sustained anti-tumorigenic effects in orthotopic glioblastoma xenografts in vivo. These results go hand in hand with genomic data from The Cancer Genome Atlas that indicate increased clotting activity and reduced patient survival in glioma subgroups with high integrin β1 and β3 expression. We therefore conclude that clotting in glioma interstitial spaces provides tumor cells with a potent proliferative stimulus that can be reversed by targeting the adhesive machinery of glioblastoma cells via inhibition of FAK.

Research on Adhesion Pull-Off Behavior of Rigid Flat Punch and Viscoelastic Substrate

Interfacial adhesion is one of the key factors affecting the reliability of micro–nano systems. The adhesion contact mechanism is still unclear as the time-dependent viscoelasticity of soft materials. To clarify the adhesion interaction, the pull-off detachment between the rigid flat punch and viscoelastic substrate is explored considering the viscoelasticity of soft materials and rate-dependent adhesion. Taking the Lennard-Jones (L-J) potential characterizing interfacial adhesion and the Prony series defining the viscoelasticity of materials as references, the bilinear cohesion zone model (CZM) and standard Maxwell model are employed, and an adhesion analysis framework is established by combining finite element technology. The influence laws of the loading and unloading rates, material relaxation coefficients and size effect on adhesion pull-off behavior are revealed. The results show that the pull-off force is independent of the material relaxation effect and related to the unloading rate. When v^ ≥ 50 or v^ < 0.01, the pull-off force has nothing to do with the unloading rate, but when 0.01 < v^ < 50, the pull-off force increases with the increasing unloading rate. Also, it is controlled by the size effect, and the changing trend conforms to the MD-n model proposed by Jiang. The energy required for interfacial separation (i.e., effective adhesion work) is a result of the comprehensive influence of unloading rates, material properties and the relaxation effect, which is consistent with Papangelo1’s research results. In addition, we derive the critical contact radius of the transition from the Kendall solution to the strength control solution. This work not only provides a detailed solution for the interfacial adhesion behavior but also provides guidance for the application of adhesion in Micro-Electro-Mechanical Systems (MEMSs).

Dan-shen Yin attenuates myocardial fibrosis after myocardial infarction in rats: molecular mechanism insights by integrated transcriptomics and network pharmacology analysis and experimental validation

Ethnopharmacological relevanceDan-shen Yin (DSY) originated from the "Shi Fang Ge Kuo" is a Chinese formula composed of three medicines: Salvia miltiorrhiza (Dan-shen), Santalum album L. (Tan-xiang) and Amomum villosum Lour. (Sha-ren). It has many years of clinical experience in the prevention of myocardial fibrosis (MF). However, the specific mechanism of DSY in prevent MF is not clear. Aim of the studyThis study aimed to assess the efficacy of DSY in the prevention of MF and reveal its underlying mechanism in a rat model of MF after myocardial infarction (MI) induced by ligation of the left anterior descending branch (LAD) of the coronary artery. Materials and methodsThe blood-entry components of DSY were analyzed by UHPLC-Q-TOF-MS/MS. LAD-ligated rats were used to assess the efficacy of DSY in the prevention of MF. Network pharmacology and transcriptomics analysis were used to predict possible target signaling pathways of DSY in MF. Echocardiography, immunohistochemistry and ELISA methods were used to evaluate the cardiac functions and biochemical changes of the rats. The mRNA expressions of target genes were measured by RT-qPCR. The proteins expressions, including Collagen I, Collagen III, α-smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP 2), matrix metallopeptidase 9 (MMP 9), transforming growth factor-β (TGF-β), protein kinase B (AKT), phospho-AKT, extracellular regulated protein kinases (ERK), phospho-ERK, c-Jun N-terminal kinase (JNK), phospho-JNK, mothers against decapentaplegic protein (Smad3), and phospho-Smad3 were detected and quantified by Western Blot. ResultsUHPLC-Q-TOF-MS/MS analysis disclosed that 20 components within DSY could be absorbed into blood of rats. DSY improved myocardial injury in the myocardial tissue of LAD-ligated rats, as evidenced by the elevation of left ventricular ejection fraction and left ventricular fractional shortening, and the decrease of the serum CK-MB and LDH levels. Network pharmacology and transcriptomics predicted that DSY could interfere biological processes, such as extracellular matrix organization, focal adhesion and ECM-receptor interaction, and modulate TGF-β mediated signaling pathways, including PI3K/AKT, MAPK, and Smad3. Further study confirmed that DSY reduced MF, accompanied by reduced TGF-β, Collagen I, Collagen III, α-SMA, MMP 2 and MMP 9. Moreover, DSY repressed the phosphorylation of AKT, MAPKs and Smad3. In addition, DSY reduced inflammation and suppressed the mRNA expressions of IL-1β, IL-6, TNF-α, COX2 and iNOS in MF rats. ConclusionsOur study demonstrated that DSY prevented MF in vivo, the action of which was probably via reducing extracellular matrix organization, focal adhesion ECM-receptor interaction and inflammation by regulating TGF-β mediated PI3K/AKT, MAPK and Smad signaling pathways.

Identification of hub genes and pathways in Uterine corpus endometrial carcinoma (UCEC): A comprehensive in silico study

BackgroundUterine corpus endometrial carcinoma (UCEC), derived from the endometrium, is the most common type of endometrial malignasis. This gynecological malignancy is very common all over the world, especially in developed countries and shows a potentially rising trend correlated with the increase in obese women. MethodsDifferentially Expressed Genes (DEGs) analysis was conducted on GSE7305 and GSE25628 datasets from the Gene Expression Omnibus (GEO). DEGs were identified using GEO2R (adjusted p-value <0.05, |logFC| > 1). Pathway analysis employed KEGG and Gene Ontology databases, while protein-protein interactions were analyzed using Cytoscape and Gephi. GEPIA was used for target gene validation. ResultsWe have identified 304 common DEGs and 78 hub genes using GEO and PPI analysis, respectively. The GO and KEGG pathways analysis revealed enrichment of DEGs in extracellular matrix structural constituent, extracellular space, cell adhesion, and ECM-receptor interaction. GEPIA analysis identified three genes, ENG, GNG4, and ECT2, whose expression significantly differed between normal and tumor samples. ConclusionThis analysis study identified the hub genes and associated pathways involved in the pathogenesis of UCEC. The identified hub genes exhibit remarkable potential as diagnostic biomarkers, providing a significant opportunity for early diagnosis and more effective therapeutic approaches for UCEC.

The influence of external and internal factors on ensuring adhesive interaction of a polymeric sealant with a substrate surface (a review)

This paper analyzes literature data on the influence of various factors affecting the strength and durability of adhesive bonds, as well as presents a characterization of the methods described in the literature for conducting relevant studies. It is shown that one of the main characteristics of adhesive joints is the interaction at the interface between the substrate and the adhesive. The adhesive capability of a sealant largely depends on the structure of the polymer component, as well as the presence of components in the sealant that enhance this property. The structure and condition of the substrate surface significantly affect the nature of the interaction between the adhesive and the substrate. Various methods are used to determine the strength of the adhesive bond, differing in the type of applied loads and the nature of the surface fracture. An important indicator is the determination of the wetting angle of the substrate by the sealant, which characterizes the surface energy. The durability of adhesive bonds is significantly influenced by environmental factors as well as operational conditions. Moisture, atmospheric oxygen, ultraviolet radiation, and microorganisms have a particularly strong effect on the properties of polymeric sealants.

Fusion of Hydrophobic Anchor Peptides Promotes the Hydrolytic Activity of PETase but not the Extent of PET Depolymerization

Enzymatic recycling of polyethylene terephthalate (PET) has attracted significant attention in recent years. While the fusion of anchor peptides to PET hydrolases is believed to enhance PET hydrolytic activity, a quantitative analysis is yet lacking. Here, we construct four fusion enzymes by fusing anchor peptides (including hydrophobic LCI, LCIM1 and TA2, and hydrophilic EK4) to the C terminus of HotPETase, one of the most active PET hydrolases for high‐crystallinity PET (HC‐PET). Single‐molecule force spectroscopy (SMFS) demonstrates that hydrophobic anchor peptides promote adhesive interactions between the fusion enzymes and the PET surface. This is also validated by the adsorption kinetics and isotherms, and the saturated adsorption capacity remains unaltered compare to HotPETase. At low substrate loadings, the apparent hydrolytic activity of these fusion enzymes is positively related to the hydrophobicity of the anchor peptides. Among them, HotPETase‐LCI stands out as the most effective enzyme for HC‐PET degradation, demonstrating a 1.5‐fold increase in hydrolytic activity. At high substrate loadings, the advantages of fusion with anchor peptides diminish. We conclude that fusion enzymes only facilitate the hydrolytic rates of HC‐PET but have little effect on the final conversion extent.

Effectiveness of self-etching bonding systems on dentin after radiotherapy: perspectives on microtensile and microshear bond strength.

Self-etching dental adhesives bond with dentin through chemical reactions with calcium. This study assessed bond strength (BS) using microtensile (µTBS) and microshear (µSBS) tests on sound and post-radiotherapy dentin, with dental adhesives containing different functional monomers. Sound dentin (SD) and post-radiotherapy irradiated dentin (ID) were tested with two adhesive systems: Clearfil SE Bond (SE, 10-MDP-based) and FL Bond II (FL, containing carboxylic and phosphonic monomers with S-PRG bioactive particles). The tests occurred initially (24h) and six months later; fracture mode was also analyzed (40x). Ninety-six human molars were randomly assigned (n = 12), and half were irradiated with a 70Gy radiation dose. ForµTBS test, teeth were bonded,restored and sectioned them into beams (0.64 mm2). The µSBS test used filled transparent cylindrical matrices with resin composite and light-cured them after dental adhesive applications. Three-way ANOVA and Tukey's test (p < 0.05) analyzed the data. µTBS showed a significant substrate x adhesive interaction (p < 0.001), while µSBS was significant for all factors (p = 0.006). SE and FL performed better on SD and ID, respectively, in the µTBS test. As for µSBS, SE showed higher values on ID (p < 0.05). Lower BS values occurred for SD-FL and ID-SE after six months. Dental adhesive performance varied based on substrate type and test method. FL was more stable for ID in µTBS, while SE excelled in µSBS. As post-radiotherapy irradiated dentin becomes more vulnerable, self-etching systems based on functional monomer and bioactive ingredients may exhibit appropriate bonding to this altered substrate.

Synergistic phenotypic adaptations of motile purple sulphur bacteria Chromatium okenii during lake-to-laboratory domestication.

Isolating microorganisms from natural environments for cultivation under optimized laboratory settings has markedly improved our understanding of microbial ecology. Artificial growth conditions often diverge from those in natural ecosystems, forcing wild isolates into distinct selective pressures, resulting in diverse eco-physiological adaptations mediated by modification of key phenotypic traits. For motile microorganisms we still lack a biophysical understanding of the relevant traits emerging during domestication and their mechanistic interplay driving short-to-long-term microbial adaptation under laboratory conditions. Using microfluidics, atomic force microscopy, quantitative imaging, and mathematical modeling, we study phenotypic adaptation of Chromatium okenii, a motile phototrophic purple sulfur bacterium from meromictic Lake Cadagno, grown under laboratory conditions over multiple generations. Our results indicate that naturally planktonic C. okenii leverage shifts in cell-surface adhesive interactions, synergistically with changes in cell morphology, mass density, and distribution of intracellular sulfur globules, to suppress their swimming traits, ultimately switching to a sessile lifeform. A computational model of cell mechanics confirms the role of such phenotypic shifts in suppressing the planktonic lifeform. By investigating key phenotypic traits across different physiological stages of lab-grown C. okenii, we uncover a progressive loss of motility during the early stages of domestication, followed by concomitant deflagellation and enhanced surface attachment, ultimately driving the transition of motile sulfur bacteria to a sessile state. Our results establish a mechanistic link between suppression of motility and surface attachment via phenotypic changes, underscoring the emergence of adaptive fitness under laboratory conditions at the expense of traits tailored for natural environments.

Protocol for the Extraction and Characterization of Trabecular Meshwork Cell Cytoskeleton Fraction.

Among various cellular attributes modulating aqueous humor (AH) outflow through the trabecular pathway and eventually intraocular pressure, the involvement of actomyosin regulated cellular contraction and relaxation, cell-extracellular matrix adhesion and cell-cell junctions, and mechanotransduction are well recognized. Although various biological and pharmacological agent-modulated AH outflows were associated with altered actin cytoskeletal organization and cell adhesive interactions of trabecular meshwork (TM) cells, these changes were analyzed largely with a biased approach to examine the specific proteins, but there were very few efforts in examining them with hypothesis-free unbiased approach in their native state. Therefore, in this chapter, we describe a protocol tailored to characterize the cytoskeleton of TM cells. This simple protocol can be applied to identifying the differentially regulated TM cell cytoskeleton proteins under any given treatment condition in conjunction with quantitative proteomic analysis.

Evolution of Peptidomimetics-Based Chiral Assemblies of β-Sheet, α-Helix, and Double Helix Involving Chalcogen Bonds.

Developing chiral assemblies that mimic biological secondary structures, e.g., protein β-sheet, α-helix, and DNA double helix, is a captivating goal in supramolecular chemistry. Here, we create a family of biomimetic chiral assemblies from alanine-based peptidomimetics, wherein the incorporation of N-terminal 2,1,3-benzoselenadiazole groups enables the rarely utilized chalcogen bonding as the adhesive interaction. While the alanine-based acylhydrazine molecule 1L was designed as a building unit with an extended conformation, simple derivatization of 1L affords folded unilateral N-amidothiourea 2L with one β-turn and bilateral N-amidothiourea 3L with two β-turns. This derivatization leads to the evolution of molecular assemblies from β-sheet organization (1L) to single helix (α-helix mimic, 2L) and ultimately to double helix (3L), illustrating an evolutionary route relating the structures and superstructures. In the case of the double helix formed by 3L, an unexpected cis-form that brings the two β-turns into one side was observed, stabilized via the π···π interaction between two N-terminal 2,1,3-benzoselenadiazole groups. This conformation allows double-crossed N-Se···S═C chalcogen bonds to support a DNA-like P-double helix featuring intrastrand noncovalent interactions and interstrand covalent linkages, surviving in both the solid state and in dilute acetonitrile solution phase.

Unique Glycans in Synaptic Glycoproteins in Mouse Brain.

The synapse is an essential connection between neuronal cells in which the membrane and secreted glycoproteins regulate neurotransmission. The post-translational modifications of glycoproteins with carbohydrates, although essential for their functions as well as their specific localization, are not well understood. Oddly, whereas galactose addition to glycoproteins is required for neuronal functions, galactosylation is severely restricted for Asn-linked on N-glycans in the brain, and genetic evidence highlights the important roles of galactose in brain functions and development. To explore this novel glycosylation, we exploited an orthogonal technology in which a biotinylated sialic acid derivative (CMP-biotin-Sia) is transferred to terminally galactosylated proteins by a recombinant sialyltransferase (rST6Gal1). This approach allowed us to identify the carrier proteins as well as their localization on brain sections. Immunohistochemical analysis of the biotinylated glycoproteins in brain sections demonstrates that they are largely positioned in the pre- and postsynaptic membranes. Consistent with this positioning, glycoproteomic analyses of the labeled glycoproteins identified a number of them that are involved in synaptic function, cell adhesion, and extracellular matrix interactions. The discovery of these galactosylated N-glycoproteins and their relative confinement to synapses provide novel insights into the unusual and specific nature of protein glycosylation in the brain.

Integration of ubiquitination-related genes in predictive signatures for prognosis and immunotherapy response in sarcoma.

Ubiquitination is one of the most prevalent and complex post-translational modifications of proteins in eukaryotes, playing a critical role in regulating various physiological and pathological processes. Targeting ubiquitination pathways, either through inhibition or activation, holds promise as a novel therapeutic approach for cancer treatment. However, the expression patterns, prognostic significance, and underlying mechanisms of ubiquitination-related genes (URGs) in sarcoma (SARC) remain unclear. We analyzed URG expression patterns and prognostic implications in TCGA-SARC using public databases, identifying DEGs related to ubiquitination among SARC molecular subtypes. Functional enrichment analysis elucidated their biological significance. Prognostic signatures were developed using LASSO-Cox regression, and a predictive nomogram was constructed. External validation was performed using GEO datasets and clinical tissue samples. The association between URG risk scores and various clinical parameters, immune response, drug sensitivity, and RNA modification regulators was investigated. Integration of data from multiple sources and RT-qPCR confirmed upregulated expression of prognostic URGs in SARC. Single-cell RNA sequencing data analyzed URG distribution across immune cell types. Prediction analysis identified potential target genes of microRNAs and long non-coding RNAs. We identified five valuable genes (CALR, CASP3, BCL10, PSMD7, PSMD10) and constructed a prognostic model, simultaneously identifying two URG-related subtypes in SARC. The UEGs between subtypes in SARC are mainly enriched in pathways such as Cell cycle, focal adhesion, and ECM-receptor interaction. Analysis of URG risk scores reveals that patients with a low-risk score have better prognoses compared to those with high-risk scores. There is a significant correlation between DRG riskscore and clinical features, immune therapy response, drug sensitivity, and genes related to pan-RNA epigenetic modifications. High-risk SARC patients were identified as potential beneficiaries of immune checkpoint inhibitor therapy. We established regulatory axes in SARC, including CALR/hsa-miR-29c-3p/LINC00943, CASP3/hsa-miR-143-3p/LINC00944, and MIR503HG. RT-qPCR data further confirmed the upregulation of prognostic URGs in SARC. Finally, we validated the prognostic model's excellent predictive performance in predicting outcomes for SARC patients. We discovered a significant correlation between aberrant expression of URGs and prognosis in SARC patients, identifying a prognostic model related to ubiquitination. This model provides a basis for individualized treatment and immunotherapy decisions for SARC patients.

Effect of Gossypol on Gene Expression in Swine Granulosa Cells.

Gossypol (GP), a polyphenolic compound in cottonseed, has notable effects on female reproduction and the respiratory system in pigs. This study aimed to discern the alterations in gene expression within swine granulosa cells (GCs) when treated with two concentrations of GP (6.25 and 12.5 µM) for 72 h, in vitro. The analysis revealed significant changes in the expression of numerous genes in the GP-treated groups. A Gene Ontology analysis highlighted that the differentially expressed genes (DEGs) primarily pertained to processes such as the mitotic cell cycle, chromosome organization, centromeric region, and protein binding. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated distinct impacts on various pathways in response to different GP concentrations. Specifically, in the GP6.25 group, pathways related to the cycle oocyte meiosis, progesterone-mediated oocyte maturation, and p53 signaling were prominently affected. Meanwhile, in the GP12.5 group, pathways associated with PI3K-Akt signaling, focal adhesion, HIF-1 signaling, cell cycle, and ECM-receptor interaction showed significant alterations. Notably, genes linked to female reproductive function (CDK1, CCNB1, CPEB1, MMP3), cellular component organization (BIRC5, CYP1A1, TGFB3, COL1A2), and oxidation-reduction processes (PRDX6, MGST1, SOD3) exhibited differential expression in GP-treated groups. These findings offer valuable insights into the changes in GC gene expression in pigs exposed to GP.

Aging affects the mechanical interaction between microplastics and lipid bilayers.

Plastic pellets, the pre-production form of many plastic products, undergo oxidation and photodegradation upon exposure to oxygen and sunlight, resulting in visible color changes. This study examines the impact of environmental aging on the mechanical interactions between pellet-derived microplastics and lipid bilayers, a critical component of biological membranes. Polyethylene pellets were collected from La Pineda beach near Tarragona, Spain, and categorized by chemical composition and yellowing index, an indicator of aging. The hydrophilicity of these pellets was assessed using contact angle measurements. Microplastics were produced by grinding and filtering these pellets and subsequently dispersed around a free-standing lipid bilayer within a 3D microfluidic chip to investigate their interactions. Our results reveal that aged microplastics exhibit a significantly increased adhesive interaction with lipid bilayers, leading to greater bilayer stretching. Theoretical modeling indicates a linear relationship between the adhesive interaction and the contact angle of the pellets, reflecting their hydrophilicity. These findings emphasize the increased mechanical impact of aged microplastics on biological membranes, which raises concerns about their potential toxicological effects on living organisms. This study highlights the importance of understanding the interactions between environmentally aged microplastics and biological systems to assess their risks, as these may differ significantly from pristine microplastics often studied under laboratory conditions.

The pan-cancer landscape presented ITGA7 as a prognostic determinant, tumor suppressor, and oncogene in multiple tumor types.

Integrin α7 (ITGA7) is an extracellular matrix-binding protein. Integrins are the main type of cell adhesive molecules in mammals, playing a role in many biological pathways. Although various studies have shown correlations between ITGA7 and various types of cancer, a comprehensive study at a pan-cancer level has not yet been conducted. In this study, we investigated the function of ITGA7 in distinct tumor types using the multi-omics relevant information, then two CeRNA regulatory network was drawn to identify the ITGA7 hub regulatory RNAs. The results indicated that the expression of ITGA7 varies in different tumors. Overexpression of ITGA7 was correlated with a worse OS in BLCA, LGG, and UVM, and the downregulation of ITGA7 was related to a worse OS in PAAD. In addition, BLCA, and UVM showed poor PFS in association with ITGA7 overexpression, and PAAD, SARC, and THCA indicated poor PFS in correlation with ITGA7 under expression. Further analyses of ITGA7 gene alteration data showed that ITGA7 amplifications may have an impact on Kidney Chromophobe prognosis. In 20 types of tumors, ITGA7 expression was linked to cancer-associated fibroblast infiltration. ITGA7 expression was linked to cancer-associated fibroblast infiltration. ITGA7-Related Gene Enrichment Analysis indicated that ITGA7 expression-correlated and functional binding genes were enriched in homotypic cell-cell adhesion, focal adhesion, and ECM-receptor interaction. This pan-cancer study found that abnormal expression of ITGA7 was correlated with poor prognosis and metastasis in different types of tumors. Thus, the ITGA7 gene may prove to be a promising biomarker for the prognosis and complication prevention of different cancers.

Synergistic effects of graphene nanoparticles on the thermomechanical properties of PEEK-HNTs nanocomposites

In our previous study, we selected a 3% concentration (PH3) from various prepared PEEK-HNTs nanocomposites. Poly (ether ether ketone) (PEEK) is characterized by non-perfluorinated aromatic compounds with 1,4-disubstituted phenyl groups linked by carbonyl (––CO––) and ether (––O––) groups, offering exceptional thermal stability, mechanical strength, tribological properties, and chemical resistance at high temperatures. Halloysite nanotubes (HNTs) are known for their non-toxic, environmentally friendly, cost-effective properties, with tunable release and rapid adsorption rates. In this study, we prepared graphene nanoparticle (GNP) composites at three different concentrations while maintaining constant PH3 levels. The composites underwent comprehensive characterization using FTIR, TGA, DSC, SEM, and DMA techniques. Thermomechanical properties were evaluated using a universal testing machine. Results demonstrate significant enhancements in hardness, impact strength, elongation at break, tensile modulus, and flexural modulus, with the highest performance observed in the GNP-loaded 0.3% (PHG3) concentration. The synergistic effects of GNP fillers in PH3 are attributed to enhanced interfacial adhesion and favorable interactions with the polymer matrix.

Potential Oncogenic and Immunosuppressive Roles of Multiple EGF-Like Domains 6 (MEGF6) in Colon Cancer: Insights from Bioinformatic Analysis

Multiple epidermal growth factor-like domains protein 6 (MEGF6) is a high molecular weight protein with several EGF-like domains. Although it has been demonstrated to promote metastasis and chemoresistance in colon cancer cells, its specific oncogenic and immunologic functions remain largely unexplored. This study aims to comprehensively analyze publicly available datasets to define the role of MEGF6 in colon cancer development and immune response modulation. The expression of MEGF6 in colon adenocarcinoma (COAD) and normal tissues at both mRNA and protein levels was assessed using the GEPIA2 and HPA databases, respectively. The UALCAN database was employed to examine the association between MEGF6 expression and clinicopathological outcomes in COAD patients, and survival analysis was conducted using the KM plotter database. Functional enrichment analysis of MEGF6-correlated genes was performed using the ShinyGO online tool. Additionally, the correlation of MEGF6 with immune cell infiltration and immunosuppressive molecules was explored through the TIMER and TISIDB databases. Our analysis revealed significantly higher mRNA and protein expressions of MEGF6 in COAD tissues compared to normal tissues, with associations to cancer stage, nodal metastasis status, and histological subtype. High MEGF6 expression was correlated with poorer survival outcomes, and genes correlated with MEGF6 were enriched in biological processes related to cellular component organization, cell adhesion, and extracellular matrix interaction. Furthermore, MEGF6 expression demonstrated a significant correlation with immune cell infiltration and the expression of immunosuppressive molecules, particularly CTLA-4, PD-1, PD-L1, TGF-β, and IL-10. In conclusion, our findings suggest that MEGF6 may play an oncogenic role by influencing cell and extracellular matrix interactions. Its overexpression may indicate immunosuppressive properties within the cancer microenvironment. Therefore, MEGF6 holds promise as a potential biomarker for predicting both prognosis and therapeutic responses in colon cancer. HIGHLIGHTS MEGF6 has been shown to involve colon cancer growth and chemotherapeutic resistance. Bioinformatics confirmed a prognostic significance of MEGF6 in colon cancer. MEGF6 may exert its oncogenic effects by influencing cell-matrix interactions. MEGF6 expression is correlated with immunosuppressive properties of cancers. GRAPHICAL ABSTRACT

Transcriptomic Profiling of Primary Microglia: Effects of miR-19a-3p and miR-19b-3p on Microglia Activation.

Neuropathic pain resulting from spinal cord injury (SCI) is a significant secondary health issue affecting around 60% of individuals with SCI. After SCI, activation of microglia, the immune cells within the central nervous system, leads to neuroinflammation by producing pro-inflammatory cytokines and affects neuropathic pain. This interplay between inflammation and pain contributes to the persistent and intense pain experienced by many individuals with SCI. MicroRNAs (miRs) have been critical regulators of neuroinflammation. Previous research in our laboratory has revealed upregulation levels of circulating miR-19a and miR-19b in individuals with SCI with neuropathic pain compared to those without pain. In this study, we treated primary microglial cultures from mice with miR-19a and miR-19b for 24 h and conducted RNA sequencing analysis. Our results showed that miR-19a and miR-19b up- and downregulate different genes according to the volcano plots and the heatmaps. miR-19a and miR-19b regulate inflammation through distinct signaling pathways. The results showed that miR-19a promotes inflammation via toll-like receptor signaling, TNF signaling, and cytokine-cytokine receptor interactions, while miR-19b increases inflammatory responses through the PI3K-Akt signaling pathway, focal adhesion, and extracellular matrix receptor interactions. The protein-protein interaction (PPI) networks used the STRING database to identify transcription factors associated with genes up- or downregulated by miR-19a and miR-19b. Key transcription factors, such as STAT1, STAT2, and KLF4 for miR-19a, and Nr4a1, Nr4a2, and Nr4a3 for miR-19b, were identified and revealed their roles in regulating neuroinflammation. This study demonstrates that miR-19a and miR-19b modulate diverse patterns of gene expression, regulate inflammation, and induce inflammatory responses in microglia.

Changes of collagen content in lung tissues of plateau yak and its mechanism of adaptation to hypoxia.

Collagen is crucial for tissue structure, functional maintenance, and cellular processes such as proliferation and differentiation. However, the specific changes in collagen expression and its associated genes in the lung tissues of yaks at high altitudes and their relationship with environmental adaptation remain poorly understood. Studying differences in the content of collagen fibers and gene expression between yaks at high (4,500 m) and low (2,600 m) altitudes, as well as between cattle at low altitudes (2,600 m). Using Masson staining, we found that the collagen fiber content in the lung tissues of yaks at low altitude was significantly higher compared to yaks at high altitude and cattle at the same altitude (P < 0.05). It was revealed through transcriptomic analyses that genes differentially expressed between high and low altitude yaks, as well as between low altitude yaks and cattle, were notably enriched in pathways related to cell adhesion, collagen synthesis, focal adhesion, and ECM-receptor interactions. Specifically, genes involved in mesenchymal collagen synthesis (e.g., COL1A1, COL1A2, COL3A1), basement membrane collagen synthesis (e.g., COL4A1, COL4A2, COL4A4, COL4A6), and peripheral collagen synthesis (e.g., COL5A1, COL6A1, COL6A2, COL6A3) were significantly upregulated in the lung tissues of yaks at low altitude compared to their high altitude counterparts and cattle (P < 0.05). In conclusion, yaks at lower altitudes exhibit increased collagen synthesis by upregulating collagen gene expression, which contributes to maintaining alveolar stability and septal flexibility. Conversely, the expression of collagen genes in yak lung tissues was down-regulated with the increase in altitude, and it was speculated that the decrease in collagen may be used to constrain the function of elastic fibers that are more abundant at high altitude, so as to enable them to adapt to the harsh environment with hypoxia and high altitude. This adaptation mechanism highlights the role of collagen in environmental acclimatization and contributes to our understanding of how altitude and species influence collagen-related physiological processes in yaks.