Search Results (31)

Background: Fluconazole (FLZ) is a broad-spectrum anti-fungal drug presenting poor flowability, mechanical properties, and limited aqueous solubility. These issues pose challenges for the handling and manufacturing of dosage forms of FLZ. The current research aimed to develop fluconazole co-crystal (CC) for improving its aqueous solubility, flowability, and mechanical properties. (2) Methods: The fluconazole benzoic acid (FLZ-BA) co-crystal was prepared using the solvent evaporation technique. The prepared co-crystal was characterized for drug content, solubility, anti-fungal activity, dissolution, and stability. DSC (Differential Scanning Calorimetry), PXRD (Powder X-Ray Diffraction), SEM (Scanning Electron Microscopy), and FTIR (Fourier Transmission Infrared) spectroscopy were carried out to confirm the co-crystal formation. The co-crystal was further evaluated for their flow characteristics and mechanical properties via CTC (compressibility, tabletability, and compactibility), Heckel, and Kawakita analysis. (3) Results: The CC showed 69.51% drug content and 13-fold greater aqueous solubility than pure FLZ. The DSC thermogram showed a sharp endothermic peak between the parent components, a distinct PXRD pattern was observed, and the SEM analysis revealed a different morphology, confirming the formation of co-crystal (new crystalline form). The CC showed immediate drug release and was found to more stable, and less hygroscopic than FLZ alone. The CC revealed better flowability, tabletability (tensile strength), compressibility, and compactibility. Moreover, Heckel and Kawakita analysis indicated the co-crystal to deform plastically, favoring improved compression. (4) Conclusions: The immediate drug release capabilities, improved hygroscopic stability, solubility, better antifungal activity, and flowability make FLZ-BA co-crystal a suitable candidate for the preparation of an immediate drug release dosage form. The study also revealed the application of co-crystal for improving the flowability and mechanical properties. Full article

Enhanced plasticity is obtained in a structurally rejuvenated Zr-based bulk metallic glass (BMG) that has been treated via cryogenic thermal cycling (CTC) for one hundred cycles. More than one primary shear band is activated due to the structural rejuvenation, which can inhibit the jerky and system-spanning propagation of shear bands to generate sluggish shear-dynamics. These are mapped to the slip statistics, including the decreased critical avalanche size, the much longer avalanche duration of large (system-spanning) slips, and a great number of small avalanches. Moreover, the universal scaling of slip avalanches for three applied stress ranges is addressed to predict the applied stress at which the failure avalanche appears most. These results indicate that slip statistics can be the fingerprints to show how much the BMG is rejuvenated, and the failure avalanche provides a good opportunity to intervene in the failure of BMGs in advance. Full article

The deformation behavior of a high-strength Mg-Al-Sn-Zn alloy under loading reversals has been thoroughly examined through a combination of experimental measurements and crystal plasticity modeling. We focused on an age-treated alloy fortified by distributed Mg₂Sn particles and Mg₁₇Al₁₂ precipitates, which underwent two distinct loading cycles: tension-compression-tension (TCT) and compression-tension-compression (CTC), aligned with the extrusion direction (ED). The initial and deformed microstructures of the alloy were analyzed using the electron backscattering diffraction (EBSD) technique. Notably, the alloy displays tensile and compressive yield strengths (YS) of 215 MPa and 160 MPa, respectively, with pronounced anelastic behavior observed during unloading and reverse loading phases. Utilizing the elasto-viscoplastic self-consistent model incorporating a twinning–detwinning scheme (EVPSC-TDT), the cyclic stress–strain responses and resultant textures of the alloy were accurately captured. The predicted alternation between various slip and twinning modes during plastic deformation was used to interpret the observed behaviors. It was found that prismatic <a> slip plays an important role during the plastic deformation of the studied alloy, and its relative activity in tensile loading processes accounts for up to ~66% and ~67% in the TCT and CTC cases, respectively. Moreover, it was discerned that detwinning and twinning behaviors are predominantly governed by stresses within the parent grain, and they can concurrently manifest during the reverse tensile loading phase in the TCT case. After cyclic deformation, the area fractions of residual twins were determined to be 7.51% and 0.93% in the TCT and CTC cases, respectively, which is a result of the varied twinning–detwinning behavior of the alloy in different loading paths. Full article

Small-cell lung cancer (SCLC) cases represent approximately 15% of all lung cancer cases, remaining a recalcitrant malignancy with poor survival and few treatment options. In the last few years, the addition of immunotherapy to chemotherapy improved clinical outcomes compared to chemotherapy alone, resulting in the current standard of care for SCLC. However, the advantage of immunotherapy only applies to a few SCLC patients, and predictive biomarkers selection are lacking for SCLC. In particular, due to some features of SCLC, such as high heterogeneity, elevated cell plasticity, and low-quality tissue samples, SCLC biopsies cannot be used as biomarkers. Therefore, the characterization of the tumor and, subsequently, the selection of an appropriate therapeutic combination may benefit greatly from liquid biopsy. Soluble factors, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) are now useful tools in the characterization of SCLC. This review summarizes the most recent data on biomarkers detectable with liquid biopsy, emphasizing their role in supporting tumor detection and their potential role in SCLC treatment choice. Full article

Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient’s condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients’ survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers. Full article

In this study, we prepare highly self-healable polymeric coating materials using charge transfer complex (CTC) interactions. The resulting coating materials demonstrate outstanding thermal stability (1 wt% loss thermal decomposition temperature at 420 °C), rapid self-healing kinetics (in 5 min), and high self-healing efficiency (over 99%), which is facilitated by CTC-induced multiple interactions between the polymeric chains. In addition, these materials exhibit excellent optical properties, including transmittance over 91% and yellow index (YI) below 2, and show enhanced weatherability with a ΔYI value below 0.5 after exposure to UV light for 72 h. Furthermore, the self-healable coating materials developed in this study show outstanding mechanical properties by overcoming the limitations of conventional self-healing materials. Full article

Plastic waste has become a big problem for the environment globally. Biodegradable polymers are a potential replacement for plastics that can have a positive outcome both environmentally and economically. In this work, we used acid hydrolysis and alkaline treatment to extract cellulose fibers from cattails. The obtained cellulose was used as a substrate for the fabrication of cellulose film using a casting technique on plastic plates. Different concentrations of the plasticizer, glycerol, were used to prepare films for comparison, and its effects on the film’s characteristics were observed. The morphology, chemical structure, and thermal stability of the cattail cellulose (CTC) films were studied using techniques such as scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and thermogravimetric analysis (TGA), respectively. Measurements of transparency, moisture content (MC), water solubility (MS), and water contact angle (WCA) were also performed. Introducing glycerol into the films increased the transparency, MC, and WS values, as well as the gap width between film textures. However, it resulted in a decrease in the WCA of the films, showing that the hydrophilicity of the films is increased by the addition of glycerol. The interaction between the functional groups of cellulose and glycerol was established from the ATR-FTIR and XRD data. The obtained results indicated that glycerol affected the thermal stability and the degree of crystallinity of the produced films. Accordingly, the hydrophilicity of the cellulose film was increased by increasing the glycerol content; therefore, cattail cellulose films can be used as a biodegradable alternative to plastic in the future. Full article

Melanoma brain metastasis (MBM) is significantly associated with poor prognosis and is diagnosed in 80% of patients at autopsy. Circulating tumor cells (CTCs) are “seeds” of metastasis and the smallest functional units of cancer. Our multilevel approach has previously identified a CTC RPL/RPS gene signature directly linked to MBM onset. We hypothesized that targeting ribogenesis prevents MBM/metastasis in CTC-derived xenografts. We treated parallel cohorts of MBM mice with FDA-approved protein translation inhibitor omacetaxine with or without CDK4/CDK6 inhibitor palbociclib, and monitored metastatic development and cell proliferation. Necropsies and IVIS imaging showed decreased MBM/extracranial metastasis in drug-treated mice, and RNA-Seq on mouse-blood-derived CTCs revealed downregulation of four RPL/RPS genes. However, mitochondrial stress tests and RT-qPCR showed that omacetaxine and palbociclib inversely affected glycolytic metabolism, demonstrating that dual targeting of cell translation/proliferation is critical to suppress plasticity in metastasis-competent CTCs. Equally relevant, we provide the first-ever functional metabolic characterization of patient-derived circulating neoplastic cells/CTCs. Full article

The exploitation of coal and the disposal of waste plastic present significant environmental and economic challenges that require sustainable and profitable solutions. In response, we propose a renewable construction composite material of coal-based thermoplastic composite (CTC) that can be made from low-grade coal and plastic waste. We developed and tested the hot-press fabrication method for this CTC, using coal with a maximum particle size of 4.75 mm and recycled high-density polyethylene (HDPE). The effects of the coal fraction (50–80 wt%) on compressive properties, thermal properties, microstructure, and ecological and economic efficiencies of the CTC were investigated. Test results revealed that the compressive strength and modulus decrease as the coal fraction increases. However, the thermal properties, including thermal conductivity and specific heat, increase with higher coal contents. Compared to concrete, the CTC has about half the thermal conductivity and twice the specific heat, making it a more energy-efficient construction material. Microstructure testing helped to reveal the mechanisms behind the above behaviors of CTC from the observation of binder volume, bonding quality between coal and HDPE, and porosity variation. The life cycle analysis indicated that the CTC production reduced embodied energy, carbon footprint, and cost by up to 84%, 73%, and 14%, respectively. Therefore, we recommend the CTC with 50–70% coal fraction as an innovative construction material with satisfied mechanical and thermal properties, better cost efficiency, and a reduced ecological impact. Full article

Circulating tumor cells (CTCs) hold unique biological characteristics that directly involve them in hematogenous dissemination. Studying CTCs systematically is technically challenging due to their extreme rarity and heterogeneity and the lack of specific markers to specify metastasis-initiating CTCs. With cutting-edge technology, single-cell RNA sequencing (scRNA-seq) provides insights into the biology of metastatic processes driven by CTCs. Transcriptomics analysis of single CTCs can decipher tumor heterogeneity and phenotypic plasticity for exploring promising novel therapeutic targets. The integrated approach provides a perspective on the mechanisms underlying tumor development and interrogates CTCs interactions with other blood cell types, particularly those of the immune system. This review aims to comprehensively describe the current study on CTC transcriptomic analysis through scRNA-seq technology. We emphasize the workflow for scRNA-seq analysis of CTCs, including enrichment, single cell isolation, and bioinformatic tools applied for this purpose. Furthermore, we elucidated the translational knowledge from the transcriptomic profile of individual CTCs and the biology of cancer metastasis for developing effective therapeutics through targeting key pathways in CTCs. Full article

Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by FOSL1) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which FOSL1 is overexpressed in the TNBC (Triple Negative Breast Cancer)/basal subtypes, correlates with the FRA-1-dependent transcriptional regulation of EMT (Epithelial-to-Mesenchymal Transition). After summarizing the major findings on FRA-1 in breast cancer invasiveness, we discuss the FRA-1 mechanistic links with EMT and cancer cell stemness, mediated by transcriptional and posttranscriptional interactions between FOSL1/FRA-1 and EMT-regulating transcription factors, miRNAs, RNA binding proteins and cytokines, along with other target genes involved in EMT. In addition to the FRA-1/AP-1 effects on the architecture of target promoters, we discuss the diagnostic and prognostic significance of the EMT-related FRA-1 transcriptome, along with therapeutic implications. Finally, we consider several novel perspectives regarding the less explored roles of FRA-1 in the tumor microenvironment and in control of the recently characterized hybrid EMT correlated with cancer cell plasticity, stemness, and metastatic potential. We will also examine the application of emerging technologies, such as single-cell analyses, along with animal models of TNBC and tumor-derived CTCs and PDXs (Circulating Tumor Cells and Patient-Derived Xenografts) for studying the FRA-1-mediated mechanisms in in vivo systems of EMT and metastasis. Full article

Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC counts decreased with therapy, and progressors had higher CTC counts than non-progressors. CTC count was prognostic primarily at the start of therapy in univariate and multivariate analyses but had less prognostic utility at 6 months to 1 year later. In contrast, gene expression, including both epithelial and mesenchymal markers, identified high-risk patients after 6–9 months of treatment, and progressors had a shift towards mesenchymal CTC gene expression on therapy. Cross-sectional analysis showed higher CTC-related gene expression in progressors 6–15 months after baseline. Furthermore, patients with higher CTC counts and CTC gene expression experienced more progression events. Longitudinal time-dependent multivariate analysis indicated that CTC count, triple-negative status, and CTC expression of FGFR1 significantly correlated with inferior progression-free survival while CTC count and triple-negative status correlated with inferior overall survival. This highlights the utility of protein-agnostic CTC enrichment and multimodality analysis to capture the heterogeneity of CTCs. Full article

Polymeric coating materials (PCMs) are promising candidates for developing next-generation flexible displays. However, PCMs are frequently subjected to external stimuli, making them highly susceptible to repeated damage. Therefore, in this study, a highly self-healing PCM based on a charge transfer complex (CTC) was developed, and its thermal, self-healing, and mechanical properties were examined. The self-healing material demonstrated improved thermal stability, fast self-healing kinetics (1 min), and a high self-healing efficiency (98.1%) via CTC-induced multiple interactions between the polymeric chains. In addition, it eliminated the trade-off between the mechanical strength and self-healing capability that is experienced by typical self-healing materials. The developed PCM achieved excellent self-healing and superior bulk (in-plane) and surface (out-of-plane) mechanical strengths compared to those of conventional engineering plastics such as polyether ether ketone (PEEK), polysulfone (PSU), and polyethersulfone (PES). These remarkable properties are attributed to the unique intermolecular structure resulting from strong CTC interactions. A mechanism for the improved self-healing and mechanical properties was also proposed by comparing the CTC-based self-healing PCMs with a non-CTC-based PCM. Full article

Stemness and epithelial–mesenchymal plasticity are widely studied in the circulating tumor cells of breast cancer patients because the roles of both processes in tumor progression are well established. An important property that should be taken into account is the ability of CTCs to disseminate, particularly the viability and apoptotic states of circulating tumor cells (CTCs). Recent data demonstrate that apoptosis reversal promotes the formation of stem-like tumor cells with pronounced potential for dissemination. Our study focused on the association between different apoptotic states of CTCs with short- and long-term treatment outcomes. We evaluated the association of viable CTCs, CTCs with early features of apoptosis, and end-stage apoptosis/necrosis CTCs with clinicopathological parameters of breast cancer patients. We found that the proportion of circulating tumor cells with features of early apoptosis is a perspective prognosticator of metastasis-free survival, which also correlates with the neoadjuvant chemotherapy response in breast cancer patients. Moreover, we establish that apoptotic CTCs are associated with the poor response to neoadjuvant chemotherapy, and metastasis-free survival expressed at least two stemness markers, CD44 and CD133. Full article

Liquid biopsies allow for the detection of cancer biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Elevated levels of these biomarkers during cancer treatment could potentially serve as indicators of cancer progression and shed light on the mechanisms of metastasis and therapy resistance. Thus, liquid biopsies serve as tools for cancer detection and monitoring through a simple, non-invasive blood draw, allowing multiple longitudinal sampling. These circulating markers have significant prospects for use in assessing patients’ prognosis, monitoring response to therapy, and developing precision medicine. In addition, single-cell omics of these liquid biopsy markers can be potential tools for identifying tumor heterogeneity and plasticity as well as novel therapeutic targets. In this review, we focus on our current understanding of circulating tumor biomarkers, especially in breast cancer, and the scope of novel sequencing technologies and diagnostic methods for better prognostication and patient stratification to improve patient outcomes. Full article