Search Results (33)

During the initial extrusion stage of the as-sintered GNPs/TA15 composite, dislocations accumulated along the GNPs and grain boundaries, leading to the formation of a subgrain structure. As extrusion progressed, these subgrains underwent rotation and transformed into finer grains through dynamic recrystallization. This process resulted in significant grain refinement, with the average grain size decreasing from 3.04 μm to 1.30 μm. Concurrently, the Ti matrix adjacent to the GNPs initially flowed towards the GNPs and subsequently elongated along the extrusion direction (ED). Furthermore, the deformed α grains experienced slip along the {10$\overline{1}$0}⟨11$\overline{2}$0⟩ system, giving rise to the development of [10$\overline{1}$1]//ED and [20$\overline{2}$1]//ED α textures. This study elucidates the influence of GNPs on the microstructural evolution, particularly in terms of grain refinement and the formation of α textures, as a function of increasing extrusion ratios. Full article

Phase transformations significantly influence the mechanical properties of Fe-based alloys, making their understanding essential for the design of high-performance alloy materials. This study investigates microstructural evolution and martensitic transformations induced by B2 phase precipitation in an Fe-20Ni-4.5Al-1.0C (wt.%) alloy. The alloy was solution-treated at 1100 °C, followed by isothermal holding between 750 °C and 1000 °C, and water quenching. Microstructural analysis revealed that the as-quenched alloy consisted of a single-phase austenite (γ). Isothermal holding led to the precipitation of a (Ni,Al)-rich B2 phase within the grains and along grain boundaries. An α′-martensitic phase was also observed within γ-grains adjacent to the B2 precipitates in the isothermally held samples. Martensitic transformation is attributed to localized nickel depletion in the matrix surrounding B2, which reduced γ-phase stability and raised the martensite start temperature (Ms), promoting γ-to-α′ transformation during cooling. The co-existence of B2 and α′ phases significantly increased the hardness of the alloy, with a maximum observed at an 850 °C holding temperature. At higher temperatures, coarsening and partial dissolution of B2, as well reduced martensite formation, led to a decline in hardness. These findings highlight the role of B2 precipitation in promoting martensitic transformation and optimizing mechanical properties through controlled heat treatment. Full article

Let us consider the finite commutative ring R, whose unity is $1\ne 0.$ Its weakly zero-divisor graph, represented as $W\Gamma \left(R\right)$, is a basic undirected graph with two distinct vertices, $c_1$ and $c_2$, that are adjacent if and only if there exist $r\in$ $\mathrm{ann}\left(c_1\right)$ and $s\in$ $\mathrm{ann}\left(c_2\right)$ that satisfy the condition $rs=0$. Let $D\left(G\right)$ be the distance matrix and $Tr\left(G\right)$ be the diagonal matrix of the vertex transmissions in basic undirected connected graph G. The $D_{\alpha }$ matrix of graph G is defined as $D_{\alpha }\left(G\right)=\alpha Tr\left(G\right)+(1-\alpha )D\left(G\right)$ for $\alpha \in [0,1]$. This article finds the $D_{\alpha }$ spectrum for the graph $W\Gamma \left({\mathbb{Z}}_n\right)$ for various values of n and also shows that $W\Gamma \left({\mathbb{Z}}_n\right)$ for $n={\vartheta }_1{\vartheta }_2{\vartheta }_3\dots {\vartheta }_t{\eta }_1^{d_1}{\eta }_2^{d_2}\dots {\eta }_s^{d_s}(d_i\ge 2,t\ge 1,s\ge 0)$, where ${\vartheta }_i$’s and ${\eta }_i$’s are the distinct primes, is $D_{\alpha }$ integral. Full article

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet’s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman’s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea’s 5-layer structure. IF examinations revealed that vimentin⁺ and α-smooth muscle actin (αSMA)⁺ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen⁺ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling. Full article

During mouse pregnancy, the pubic symphysis (PS) undergoes a gradual transitioning into an interpubic ligament (IpL) for a successful delivery. After birth, this IpL is rapidly remodeled, returning to the non-pregnant morphology. The PS fibrocartilaginous cells acquire a myofibroblast-like phenotype, characterized by extracellular matrix (ECM) secretion, expression of α-smooth muscle actin (α-SMA), and vimentin. While the presence of myofibroblast-like cells during the IpL remodeling is well described, cell–cell interactions and how this might contribute to the delivery remains poorly understood. This study uses ultrastructure and molecular approaches to investigate cell–cell and cell–ECM junctions during mouse pregnancy and postpartum. Our findings reveal that the intercellular contacts between adjacent IpL myofibroblast-like cells, particularly at late pregnancy stages, are characterized as adherens and GAP junctions. The acquisition of contractile elements by IpL cells, coupled with neighboring cells and the surrounding ECM via junctional complexes, suggests an important role in supporting changes in the mechanical forces generated by pubic bone movements during mouse pregnancy and also in tying the pelvic bones together, which may help the birth canal closure after delivery. Further studies in PS biology may investigate fibroblast to myofibroblast differentiation signaling cascades, which regulate the expression of pro-fibrotic proteins and may provide new insights for preterm labor. Full article

Telocytes (TCs) are distinctive cells widely localized in the stromal compartment of several human organs, including the skin. By means of their peculiar prolongations named telopodes, skin TCs are organized in networks interconnected with a variety of adjacent cells, being thus supposed to take part in skin homeostasis through both cell-to-cell contacts and the release of extracellular vesicles. A disarrangement/loss of the TC network was shown in human fibrotic skin as well as in the murine model of bleomycin-induced cutaneous fibrosis, but whether such TC alterations may represent just a consequence or a trigger of the fibrotic process still remains to be clarified. Thus, we investigated the effects of skin TC secretome as conditioned medium (TC-CM) on the transition of skin fibroblasts into myofibroblasts promoted by the master profibrotic cytokine transforming growth factor β1 (TGFβ1). Primary cultures of both adult human skin TCs and fibroblasts were obtained by means of immunomagnetic cell separation. Nanoparticle tracking analysis was carried out to measure extracellular vesicles in TC-CM. The combination of multiple morphological, gene/protein expression, and functional assessments demonstrated that TC-CM was able to significantly prevent TGFβ1-induced fibroblast-to-myofibroblast transition. TC-CM did not influence cell viability, while it effectively inhibited TGFβ1-induced fibroblast proliferation, migration, and morphological changes. Indeed, TC-CM was able to reduce TGFβ1-mediated skin fibroblast phenotypic and functional differentiation into myofibroblasts, as shown by a significant decrease in FAP, ACTA2, COL1A1, COL1A2, FN1, and CTGF gene expression, α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein levels, and collagen gel matrix contraction. Furthermore, TC-CM significantly lowered TGFβ1-mediated ERK1/2 signaling pathway activation. This in vitro study proves for the first time that TCs may play an important role in skin homeostasis through the prevention of fibroblast-to-myofibroblast transition via paracrine mechanisms and affords the necessary basis to investigate in the future the feasibility of TC secretome as an innovative antifibrotic therapeutic tool. Full article

In 2017, Nikiforov defined the $A_{\alpha }$-matrix of the graph G as $A_{\alpha }\left(G\right)=\alpha D\left(G\right)+(1-\alpha )A\left(G\right),0\le \alpha \le 1,$ which merges the diagonal degree matrix $D\left(G\right)$ and the adjacency matrix $A\left(G\right)$. In this paper, we characterize the graphs which attain the maximum $A_{\alpha }$-index among triangle-free non-bipartite graphs of order n for $1/2<\alpha <1$. Full article

New data, including Raman spectroscopy, characterize unusual mineral assemblages from rocks of the Naylga and Khamaryn–Khyral–Khiid combustion metamorphic complexes in Mongolia. Several samples of melilite–nepheline paralava and other thermally altered (metamorphosed) sedimentary rocks contain troilite (FeS), metallic iron Fe⁰, kamacite α-(Fe,Ni) or Ni-bearing Fe⁰, taenite γ-(Fe,Ni) or Ni-rich Fe⁰, barringerite or allabogdanite Fe₂P, schreibersite Fe₃P, steadite Fe₄P = eutectic α-Fe + Fe₃P, wüstite FeO, and cohenite Fe₃C. The paralava matrix includes a fragment composed of magnesiowüstite–ferropericlase (FeO–MgO solid solution), as well as of spinel (Mg,Fe)Al₂O₄ and forsterite. The highest-temperature mineral assemblage belongs to a xenolithic remnant, possibly Fe-rich sinter, which is molten ash left after underground combustion of coal seams. The crystallization temperatures of the observed iron phases were estimated using phase diagrams for the respective systems: Fe–S for iron sulfides and Fe–P ± C for iron phosphides. Iron monosulfides (high-temperature pyrrhotite) with inclusions of Fe⁰ underwent solid-state conversion into troilite at 140 °C. Iron phosphides in inclusions from the early growth zone of anorthite–bytownite in melilite–nepheline paralava crystallized from <1370 to 1165 °C (Fe₂P), 1165–1048 °C (Fe₃P), and <1048 °C (Fe₄P). Phase relations in zoned spherules consisting of troilite +Fe⁰ (or kamacite + taenite) +Fe₃P ± (Fe₃C, Fe₄P) reveal the potential presence of a homogeneous Fe–S–P–C melt at T~1350 °C, which separated into two immiscible melts in the 1350–1250 °C range; namely, a dense Fe–P–C melt in the core and a less dense Fe–S melt in the rim. The melts evolved in accordance with cooling paths in the Fe–S and Fe–P–C phase diagrams. Cohenite and schreibersite in the spherules crystallized between 988 °C and 959 °C. The crystallization temperatures of minerals were used to reconstruct redox patterns with respect to the CCO, IW, IM, and MW buffer equilibria during melting of marly limestone and subsequent crystallization and cooling of melilite–nepheline paralava melts. The origin of the studied CM rocks was explained in a model implying thermal alteration of low-permeable overburden domains in reducing conditions during wild subsurface coal fires, while heating was transferred conductively from adjacent parts of ignited coal seams. The fluid (gas) regime in the zones of combustion was controlled by the CCO buffer at excess atomic carbon. Paralava melts exposed to high-temperature extremely reducing conditions contained droplets of immiscible Fe–S–P–C, Fe–S, Fe–P, and Fe–P–C melts, which then crystallized into reduced mineral assemblages. Full article

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms’ pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes. Full article

In colorectal cancer (CRC), attempts to identify cancer cell-specific markers to guide antibody-mediated therapeutics have failed to uncover markers that are both exclusive to cancer tissues and abundant across CRCs. Alternatively, cancer-associated fibroblasts (CAFs), which are abundant in the tumor microenvironment and upregulate unique surface markers, are not found in healthy tissues. Here, we evaluated the expression patterns of CAF-associated proteins α-smooth muscle actin (αSMA), fibroblast activation protein (FAP), podoplanin (PDPN), matrix metalloproteinase-2 (MMP2), transgelin (TAGLN), and THY1. While αSMA and THY1 were abundant in cancer tissues, high abundance in normal tissues limited their targeting potential. FAP was present in 94.5% of primary and metastatic CRC tissues and absent in 93.7% of adjacent normal colon and liver tissues assessed. These results indicate that FAP is a promising target for antibody conjugates with potential for broad application in CRC. Co-expression analyses showed that CRCs simultaneously expressing high levels of PDPN, MMP2, and THY1 were enriched for immune-related signatures, indicating potential for antibody-mediated immune engagers. Overall, this work highlights the potential of CAF proteins to act as therapeutic targets for novel anticancer agents and become important therapeutic biomarkers. Full article

Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147–CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3′UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells—macrophages, dendritic cells, and B cells. The aim of the study is to test genotype–phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy—it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well. Full article

Let G be a graph with the adjacency matrix $A\left(G\right)$, and let $D\left(G\right)$ be the diagonal matrix of the degrees of G. Nikiforov first defined the matrix $A_{\alpha }\left(G\right)$ as $A_{\alpha }\left(G\right)=\alpha D\left(G\right)+(1-\alpha )A\left(G\right)$, $0\le \alpha \le 1$, which shed new light on $A\left(G\right)$ and $Q\left(G\right)=D\left(G\right)+A\left(G\right)$, and yielded some surprises. The $\alpha -$adjacency energy $E^{A_{\alpha }}\left(G\right)$ of G is a new invariant that is calculated from the eigenvalues of $A_{\alpha }\left(G\right)$. In this work, by combining matrix theory and the graph structure properties, we provide some upper and lower bounds for $E^{A_{\alpha }}\left(G\right)$ in terms of graph parameters (the order n, the edge size m, etc.) and characterize the corresponding extremal graphs. In addition, we obtain some relations between $E^{A_{\alpha }}\left(G\right)$ and other energies such as the energy $E\left(G\right)$. Some results can be applied to appropriately estimate the $\alpha$-adjacency energy using some given graph parameters rather than by performing some tedious calculations. Full article

Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of retinal pigment epithelium (RPE) adjacent to the ONH. Under pro-fibrotic conditions, epithelial cells throughout the body can differentiate into fibroblast-like cells through epithelial-to-mesenchymal transition (EMT) and contribute to ECM fibrosis. This is investigated here in the context of glaucoma and PPA. Human-donor ONH sections were assessed for the presence of the RPE cell-specific marker RPE65 using immunofluorescence. We examined the EMT response of ARPE-19 cells to the following glaucoma-related stimuli: cyclic mechanical stretch, mechanical stiffness, transforming growth factor beta (TGFβ), and tumour necrosis factor alpha (TNFα). The gene expression was measured using the PCR of the epithelial tight junction marker zona occludens 1 (ZO-1) and the mesenchymal markers alpha smooth muscle actin (αSMA) and vimentin. A scratch assay was used to assess the ARPE-19 migration. Significant RPE-65 staining was demonstrated in the glaucomatous ONH. The cyclic stretching and substrate stiffness of the ARPE-19 cells caused a significant decrease in ZO-1 (p = 0.04), and an increase in αSMA (p = 0.04). The scratch assays demonstrated increased migration of ARPE19 in the presence of TNFα (p = 0.02). Furthermore, ARPE-19 cells undergo an EMT-like transition (gain of αSMA, loss of ZO-1 and increased migration) in response to glaucomatous stimuli. This suggests that during PPA, RPE cells have the potential to migrate into the ONH and differentiate into fibroblast-like cells, contributing to glaucomatous ONH cupping. Full article

Current advances in molecular profiling methodologies and the accessibility of multi-omics datasets are paving the way toward a better understanding of heterogeneous diseases, including breast cancer (BC). In this regard, we sought to uncover the transcriptional changes triggered by estrogen and insulin in a primary BC cell line (BCAHC-1), which expresses the 46kDa isoform of the estrogen receptor (ER)α and the insulin receptor, as we have previously ascertained. Raw data from RNA sequencing of BCAHC-1 cells were processed by the Bcl2Fastq 2.20 version of the Illumina pipeline, while in silico analyses were performed in R Studio using the TCGA dataset. Real-time PCR, immunoblotting, ELISA and chromatin immunoprecipitation experiments were used to identify the molecular events triggered by estrogen and insulin in BCAHC-1 cells and cancer-associated fibroblasts (CAFs). Furthermore, migration and invasion assays allowed us to ascertain the mechanisms triggering these biological responses in the presence of the aforementioned hormone treatments. First, we determined that 17β-estradiol (E2) and insulin stimulate a peculiar IL-11 expression and IL-11 secretion in BCAHC-1 cells. Thereafter, bioinformatics analyses confirmed the up-regulation of IL-11 in ER-positive BCs, with respect to adjacent normal tissues, and its association with worse survival. Next, the involvement of IL-11 in pro-metastatic transduction signaling was established via pathway enrichment analyses. Notably, we found that the secretion of IL-11 by BCAHC-1 cells prompts an invasive phenotype of CAFs through the up-regulation of genes belonging to the extracellular matrix organization pathway, namely, the intercellular adhesion molecule 1 and integrin alpha 5. Overall, our findings indicate that IL-11 secretion by BC cells may elicit a paracrine action on the surrounding stroma and introduce invasive properties, suggesting that IL-11 could be considered a valuable target in comprehensive treatments of ER-positive BC patients. Full article

For a simple finite graph G, the generalized adjacency matrix is defined as ${\mathcal{A}}_{\alpha }\left(G\right)=\alpha \mathcal{D}\left(G\right)+(1-\alpha )A\left(G\right),\alpha \in [0,1]$, where $A\left(G\right)$ and $\mathcal{D}\left(G\right)$ are respectively the adjacency matrix and diagonal matrix of the vertex degrees. The $A_{\alpha }$-spread of a graph G is defined as the difference between the largest eigenvalue and the smallest eigenvalue of the ${\mathcal{A}}_{\alpha }\left(G\right)$. In this paper, we answer the question posed in (Lin, Z.; Miao, L.; Guo, S. Bounds on the $A_{\alpha }$-spread of a graph. Electron. J. Linear Algebra 2020, 36, 214–227). Furthermore, we show that the path graph, $P_n$, has the smallest $\mathcal{S}\left({\mathcal{A}}_{\alpha }\right)$ among all trees of order n. We establish a relationship between $\mathcal{S}\left({\mathcal{A}}_{\alpha }\right)$ and $\mathcal{S}\left(A\right).$ We obtain several bounds for $\mathcal{S}\left({\mathcal{A}}_{\alpha }\right)$. Full article