Search Results (13)

This study employs numerical simulations and experiments to examine the cold spray deposition of nanostructured hydroxyapatite (Ca₁₀(PO4)₆(OH)₂, HA)/70wt.%Ti composite particles under different processing conditions, based on the features of nanocomposites that strengthen interfacial adhesion and improve coating interfacial strength. Using ABAQUS/CAE combined with LS-PrePost 4.9-x64 software, the deposition behavior of the composite particles during deposition under various impact velocities was analyzed, along with the stress of the HA and Ti particles within the composite particle. The deposition behavior of both single and multiple composite particles under different gas temperatures was studied through cold spray experiments, and composite coatings were fabricated. The microstructure and phase composition were analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results showed that the numerical simulations were consistent with the experimental analyses. As the particle velocity or gas temperature increased, the degree of particle deformation upon deposition became more pronounced, accompanied by phenomena such as cracking or fragmentation and splashing rebound. At a gas temperature of 700 °C, both the bonding density of individual particles and the bonding effectiveness of multi-particle deposits were lower than those achieved at 500 °C. The coating prepared at a gas temperature of 500 °C exhibited a flatter surface, better overall bonding with the Ti interlayer, and higher internal density. Full article

Type 2 Diabetes Mellitus (T2DM) is increasingly affecting individuals across various age groups due to inadequate insulin action and secretion. It has become the leading cause of mortality worldwide, with an estimated 9.3% of the global population currently affected. Recent epigenetic studies have shown that variations such as DNA methylation and histone modifications are implicated in the development of T2DM. However, epigenetically related conditions are known to be reversible, which could potentially pave the way for predicting and treating T2DM. This has led to the development of epigenetic modifier drugs, including histone deacetylase inhibitors (HDACi), histone acetyltransferase inhibitors (HATi), protein arginine methyltransferase inhibitors (PRMTi), DNA methyltransferase inhibitors (DNMTi), histone demethylating inhibitors (HDMi), and sirtuin-activating compounds (STAC). A major challenge with these epigenetic drugs is that only a few have been approved for treating metabolic diseases due to their potential to negatively impact off-target genes. The low specificity of these drugs can lead to side effects and increased toxicity, contributing to complex diseases such as cancer. Hence, gaining a comprehensive understanding of the epigenetic mechanisms underlying metabolic diseases can provide new insights and strategies for preventing, diagnosing, and treating metabolic disorders, such as T2DM. This review summarizes the epigenetic variations in T2DM, pharmaco-epigenetics, and the challenges surrounding epigenetics. This provides basic insight into the discovery of novel drug targets, which can lead to the development of epigenetic therapies for T2DM. Hence, the reversible nature of epigenetic variations retains hope for future novel strategies to combat T2DM. Full article

We analyze the high-order above-threshold ionization (HATI) process of a small polyatomic molecule with C₃ symmetry, which is induced by a bicircular strong laser field. This field consists of two coplanar, counter-rotating, circularly polarized components with frequencies $r\omega$ and $s\omega$ where r and s are integers. In our study, we use an improved molecular strong-field approximation to obtain electron energy-angle-resolved and momentum spectra of the BF₃ molecule. We analyze the contributions of individual atoms as well as the impact of molecular symmetries on these spectra. We find that these spectra are significantly affected by the characteristics of the molecule and the laser-field parameters. Furthermore, we observe pronounced interference minima in the HATI spectra. We demonstrate that these minima result from the destructive interference of rescattered wave packets from different atomic centers, and we determine the conditions under which they occur, including two-, three-, and four-center interference. Full article

Hydroxyapatite (HA, Ca₁₀(PO₄)₆(OH)₂) composite coatings added in the second phase could improve the mechanical properties and bonding strength. The cold spraying technique, as a technology for the deposition of solid particles at low temperatures, is employed to deposit HA ceramic composite coatings. The nano HA material possesses characteristics that enhance properties and promote interface bonding. Due to the exceptional mechanical properties of Ti material, adding Ti particles could improve the mechanical properties of nano HA/Ti composite coatings. In order to explore the deposition deformation mechanism of composite particles under different cold spraying conditions, numerical simulation and experimental testing of deposition behaviors of dual nano HA/Ti composite particles were analyzed. As the particle velocity increased from 400 m/s to 800 m/s in the numerical simulation analysis, the more serious the deposition deformation. Meanwhile, more cracking and splashing phenomena occurred on the surface of the particle. By analyzing the stress value curve of Ti and HA units under different particle velocities, it was found that the adiabatic shear instability phenomenon occurred during the particle deposition on the substrate. In addition, the degree of particle deformation increased with the decrease in the particle size. The results of the experimental investigation were consistent with that of the numerical simulation. Full article

To improve the performance of porous hydroxyapatite/titanium (HA/Ti) composites, LaF₃ reinforced porous HA/Ti scaffolds with a porosity of approximately 60% were prepared via a powder metallurgical method, using NH₄HCO₃ as the pore-forming agent. The scaffolds induced HA formation and showed high bioactivity, and the compressive strength could be regulated by changing the LaF₃ dosage. When the LaF₃ dosage was 0.3%, the compressive strength of the porous scaffold was 65 MPa. Moreover, LaF₃ reinforced porous HA/Ti scaffolds can further induce the deposition of calcium phosphate after immersion in simulated body fluid (SBF) for 7 days, indicating that the corresponding scaffold is an ideal choice for spongy bone repair. Full article

Rhabdomyosarcoma (RMS) is a malignant tumour of the soft tissues. There are two main histopathological types: alveolar and embryonal. RMS occurs mainly in childhood and is a result of the deregulation of growth and differentiation of muscle cell precursors. There is an increasing amount of data indicating that numerous epigenetic alterations within chromatin and histone proteins are involved in the pathogenesis of this malignancy. Histone acetylation is one of the most important epigenetic modifications that is catalysed by enzymes from the group of histone acetyltransferases (HAT). In this study, the impact of the natural histone acetyltransferase inhibitors (HATi)—garcinol (GAR) and anacardic acid (AA)—on the biology of RMS cells was evaluated through a series of in vitro tests measuring proliferation, viability, clonogenicity, cell cycle and apoptosis. Moreover, using oligonucleotide microarrays and real-time PCR, we identified several genes whose expression changed after GAR and AA treatment. The examined HATi significantly reduce the invasive phenotype of RMS cells by inhibiting the growth rate, viability and clonogenic abilities. What is more, these substances cause cell cycle arrest in the G2/M phase, induce apoptosis and affect the genetic expression of the endoplasmic reticulum stress sensors. GAR and AA may serve as promising potential anti-cancer drugs since they sensitize the RMS cells to chemotherapeutic treatment. Full article

The polygenic nature of neurological and psychiatric syndromes and the significant impact of environmental factors on the underlying developmental, homeostatic, and neuroplastic mechanisms suggest that an efficient therapy for these disorders should be a complex one. Pharmacological interventions with drugs selectively influencing the epigenetic landscape (epidrugs) allow one to hit multiple targets, therefore, assumably addressing a wide spectrum of genetic and environmental mechanisms of central nervous system (CNS) disorders. The aim of this review is to understand what fundamental pathological mechanisms would be optimal to target with epidrugs in the treatment of neurological or psychiatric complications. To date, the use of histone deacetylases and DNA methyltransferase inhibitors (HDACis and DNMTis) in the clinic is focused on the treatment of neoplasms (mainly of a glial origin) and is based on the cytostatic and cytotoxic actions of these compounds. Preclinical data show that besides this activity, inhibitors of histone deacetylases, DNA methyltransferases, bromodomains, and ten-eleven translocation (TET) proteins impact the expression of neuroimmune inflammation mediators (cytokines and pro-apoptotic factors), neurotrophins (brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF)), ion channels, ionotropic receptors, as well as pathoproteins (β-amyloid, tau protein, and α-synuclein). Based on this profile of activities, epidrugs may be favorable as a treatment for neurodegenerative diseases. For the treatment of neurodevelopmental disorders, drug addiction, as well as anxiety disorders, depression, schizophrenia, and epilepsy, contemporary epidrugs still require further development concerning a tuning of pharmacological effects, reduction in toxicity, and development of efficient treatment protocols. A promising strategy to further clarify the potential targets of epidrugs as therapeutic means to cure neurological and psychiatric syndromes is the profiling of the epigenetic mechanisms, which have evolved upon actions of complex physiological lifestyle factors, such as diet and physical exercise, and which are effective in the management of neurodegenerative diseases and dementia. Full article

With the increasing deployment of autonomous taxis in different cities around the world, recent studies have stressed the importance of developing new methods, models and tools for intuitive human–autonomous taxis interactions (HATIs). Street hailing is one example, where passengers would hail an autonomous taxi by simply waving a hand, exactly like they do for manned taxis. However, automated taxi street-hailing recognition has been explored to a very limited extent. In order to address this gap, in this paper, we propose a new method for the detection of taxi street hailing based on computer vision techniques. Our method is inspired by a quantitative study that we conducted with 50 experienced taxi drivers in the city of Tunis (Tunisia) in order to understand how they recognize street-hailing cases. Based on the interviews with taxi drivers, we distinguish between explicit and implicit street-hailing cases. Given a traffic scene, explicit street hailing is detected using three elements of visual information: the hailing gesture, the person’s relative position to the road and the person’s head orientation. Any person who is standing close to the road, looking towards the taxi and making a hailing gesture is automatically recognized as a taxi-hailing passenger. If some elements of the visual information are not detected, we use contextual information (such as space, time and weather) in order to evaluate the existence of implicit street-hailing cases. For example, a person who is standing on the roadside in the heat, looking towards the taxi but not waving his hand is still considered a potential passenger. Hence, the new method that we propose integrates both visual and contextual information in a computer-vision pipeline that we designed to detect taxi street-hailing cases from video streams collected by capturing devices mounted on moving taxis. We tested our pipeline using a dataset that we collected with a taxi on the roads of Tunis. Considering both explicit and implicit hailing scenarios, our method yields satisfactory results in relatively realistic settings, with an accuracy of 80%, a precision of 84% and a recall of 84%. Full article

HA composite coatings added reinforcement phases could improve the mechanical properties and bonding strength of the coatings. Cold spraying is a feasible surface technology for preparing HA composite coatings. In order to investigate the influence of cold spraying parameters on the deposition behavior of a single HA/Ti composite particle, numerical and experimental investigation of gas-particle two-phase flow in cold spraying nanostructured HA/Ti composite particle were investigated in this study. The results show that the influence of different temperatures and pressures on static pressure was not significant. The effects of gas pressure on the static temperature were tiny under the same inlet temperature and different pressure conditions; however, the static temperature in the entire spray gun cavity increased as the inlet temperature increased under the same pressure and different inlet temperature conditions. There is little effect of gas pressure on the axial velocity of gas flow in the spray gun cavity; however, the axial velocity of gas flow increased with the increase in gas temperature. Meanwhile, the axial velocity of gas flow gradually increases throughout the spraying process. At a gas temperature of 573 K and 973 K, the maximum axial velocities of a gas flow at gas pressure of 2.2 MPa were 778 m/s and 942 m/s, respectively. There is little effect of gas pressure on the axial velocity of HA/30 wt.% Ti particles under the same gas temperature. The axial velocity of HA/30 wt.% Ti particles increased with the increase in gas temperature under the same gas pressure condition. The axial velocity of composite particles decreased with the increase in the particle size under the same gas pressure and gas temperature. At a gas temperature of 573 K and 973 K, the minimum axial velocity of HA/30 wt.% Ti particles with a particle size of 30 μm at a gas pressure of 2.2 MPa was 435 m/s and 467 m/s, respectively. A certain deformation of splats occurred after impacting the substrate, and the splats adhered to the surface of the Ti6Al4Vsubstrate, clearly presenting a flat shape with a central hump surrounded by a ringy band. At a gas temperature of 973 K, particles generated more severe deformation with more cracks and ejecta phenomenon. The splats attached to the substrate were increased as the gas temperature increased. Full article

Accumulating evidence (mainly from experimental research) suggests that metformin possesses anticancer properties through the induction of apoptosis and inhibition of the growth and proliferation of cancer cells. However, its effect on the enzymes responsible for histone acetylation status, which plays a key role in carcinogenesis, remains unclear. Therefore, the aim of our study was to evaluate the impact of metformin on histone acetyltransferases (HATs) (i.e., p300/CBP-associated factor (PCAF), p300, and CBP) and on histone deacetylases (HDACs) (i.e., SIRT-1 in human pancreatic cancer (PC) cell lines, 1.2B4, and PANC-1). The cells were exposed to metformin, an HAT inhibitor (HATi), or a combination of an HATi with metformin for 24, 48, or 72 h. Cell viability was determined using an MTT assay, and the percentage of early apoptotic cells was determined with an Annexin V-Cy3 Apoptosis Detection Assay Kit. Caspase-9 activity was also assessed. SIRT-1, PCAF, p300, and CBP expression were determined at the mRNA and protein levels using RT-PCR and Western blotting methods, respectively. Our results reveal an increase in caspase-9 in response to the metformin, indicating that it induced the apoptotic death of both 1.2B4 and PANC-1 cells. The number of cells in early apoptosis and the activity of caspase-9 decreased when treated with an HATi alone or a combination of an HATi with metformin, as compared to metformin alone. Moreover, metformin, an HATi, and a combination of an HATi with metformin also modified the mRNA expression of SIRT-1, PCAF, CBP, and p300. However, metformin did not change the expression of the studied genes in 1.2B4 cells. The results of the Western blot analysis showed that metformin diminished the protein expression of PCAF in both the 1.2B4 and PANC-1 cells. Hence, it appears possible that PCAF may be involved in the metformin-mediated apoptosis of PC cells. Full article

Among Histone post-translational modifications (PTMs), lysine acetylation plays a pivotal role in the epigenetic regulation of gene expression, mediated by chromatin modifying enzymes. Due to their activity in physiology and pathology, several chemical compounds have been developed to inhibit the function of these proteins. However, the pleiotropy of these classes of proteins represents a weakness of epigenetic drugs. Ideally, a new generation of epigenetic drugs should target with molecular precision individual acetylated lysines on the target protein. We exploit a PTM-directed interference, based on an intrabody (scFv-58F) that selectively binds acetylated lysine 9 of histone H3 (H3K9ac), to test the hypothesis that targeting H3K9ac yields more specific effects than inhibiting the corresponding HAT enzyme that installs that PTM. In yeast scFv-58F modulates, gene expression in a more specific way, compared to two well-established HAT inhibitors. This PTM-specific interference modulated expression of genes involved in ribosome biogenesis and function. In mammalian cells, the scFv-58F induces exclusive changes in the H3K9ac-dependent expression of specific genes. These results suggest the H3K9ac-specific intrabody as the founder of a new class of molecules to directly target histone PTMs, inverting the paradigm from inhibiting the writer enzyme to acting on the PTM. Full article

Growth Factor Independence 1 (GFI1) is a transcription factor with an important role in the regulation of development of myeloid and lymphoid cell lineages and was implicated in the development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Reduced expression of GFI1 or presence of the GFI1-36N (serine replaced with asparagine) variant leads to epigenetic changes in human and murine AML blasts and accelerated the development of leukaemia in a murine model of human MDS and AML. We and other groups previously showed that the GFI1-36N allele or reduced expression of GFI1 in human AML blasts is associated with an inferior prognosis. Using GFI1-36S, -36N -KD, NUP98-HOXD13-tg mice and curcumin (a natural histone acetyltransferase inhibitor (HATi)), we now demonstrate that expansion of GFI1-36N or –KD, NUP98-HODXD13 leukaemic cells can be delayed. Curcumin treatment significantly reduced AML progression in GFI1-36N or -KD mice and prolonged AML-free survival. Of note, curcumin treatment had no effect in GFI1-36S, NUP98-HODXD13 expressing mice. On a molecular level, curcumin treatment negatively affected open chromatin structure in the GFI1-36N or -KD haematopoietic cells but not GFI1-36S cells. Taken together, our study thus identified a therapeutic role for curcumin treatment in the treatment of AML patients (homo or heterozygous for GFI1-36N or reduced GFI1 expression) and possibly improved therapy outcome. Full article

Along with genetic mutations, aberrant epigenetic alterations are the initiators of head and neck cancer carcinogenesis. Currently, several drugs are being developed to correct these epigenetic alterations, known as epidrugs. Some compounds with an antioxidant effect have been shown to be effective in preventing these malignant lesions and in minimizing the complications derived from cytotoxic treatment. Furthermore, in vitro and in vivo studies show a promising role in the treatment of head and neck squamous cell carcinoma (HNSCC). This is the case of supplements with DNA methylation inhibitory function (DNMTi), such as epigallocatechin gallate, sulforaphane, and folic acid; histone deacetylase inhibitors (HDACi), such as sodium butyrate and melatonin or histone acetyltransferase inhibitors (HATi), such as curcumin. The objective of this review is to describe the role of some antioxidants and their epigenetic mechanism of action, with special emphasis on melatonin and butyric acid given their organic production, in the prevention and treatment of HNSCC. Full article