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To evaluate the properties of two nickel-titanium (NiTi) reciprocating endodontic instruments (commercially known as Procodile and Reziflow), a total of 40 size 25 and 0.06 taper new Procodile and Reziflow instruments (n = 20) were subjected to cyclic fatigue tests (60° angle of curvature, 5-mm radius) at 20 °C and 37 °C and a torsional test based on ISO 3630-1. The fracture surface of each fragment was examined. The morphological, mechanical, chemical, thermal, and phase composition characteristics of the files were investigated by field-emission gun scanning electron microscopy (FEG-SEM) equipped with an energy-dispersive X-ray (EDX) detector, focused ion beam analysis (FIB), micro-Raman spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Auger electron spectroscopy (AES). Reziflow showed higher cyclic fatigue resistance than Procodile at 37 °C (p 0.05). SEM, FIB, Micro-Raman, and AES analyses revealed the presence of an Nb/Nb2O5 coating on the Procodile surface. DSC and XRD analysis confirmed that both files consist of an almost austenitic phase structure at 37 °C. The cyclic fatigue resistance of Procodile and Reziflow significantly decreases upon exposure to body temperature.Frangula alnus and Peganum harmala populations growing in Saudi Arabia might be rich sources of natural compounds with important biological activities. A high performance liquid chromatography diode array revealed several polyphenols in the leaf extracts for the first time, including p-coumaric acid, rosmarinic acid, chlorogenic acid, ferulic acid, quercitrin, rutoside, quercetin and trifolin in F. alnus; and hydrocaffeic acid, protocatechuic acid, rosmarinic acid, caffeic acid and cynaroside in P. harmala. F. alnus and P. harmala showed strong antioxidant effects attributed to the polyphenolic composition of leaves and reduction of reactive oxygen species (ROS) accumulation. [https://www.selleckchem.com/products/mdl-800.html selleck inhibitor] F. alnus and P. harmala leaf extracts showed cytotoxic effects against Jurkat, MCF-7, HeLa, and HT-29 cancer cells using MTT and flow cytometry assays. These activities were attributed to the polyphenolic composition of leaves including quercitrin, trifolin and cymaroside, as well as the activation of caspase family enzymes 2, 6, 8 and 9 in treated cancer cells compared to control. The current findings of this study include a novel comprehensive investigation on the polyphenol composition and anticancer effects of leaf extracts of F. alnus and P. harmala from natural populations in Saudi Arabia.We report the design, synthesis, and physicochemical properties of an array of phenanthro[2,1-b7,8-b']dithiophene (PDT-2) derivatives by introducing five types of alkyl (CnH2n+1; n = 8, 10, 12, 13, and 14) or two types of decylthienyl groups at 2,7-positions of the PDT-2 core. Systematic investigation revealed that the alkyl length and the type of side chains have a great effect on the physicochemical properties. For alkylated PDT-2, the solubility was gradually decreased as the chain length was increased. For instance, C8-PDT-2 exhibited the highest solubility (5.0 g/L) in chloroform. Additionally, substitution with 5-decylthienyl groups showed poor solubility in both chloroform and toluene, whereas PDT-2 with 4-decylthienyl groups resulted in higher solubility. Furthermore, UV-vis absorption of PDT-2 derivatives substituted by decylthienyl groups showed a redshift, indicating the extension of their π-conjugation length. This work reveals that modification of the conjugated core by alkyl or decylthienyl side chains may be an efficient strategy by which to change the physicochemical properties, which might lead to the development of high-performance organic semiconductors.The unique structure and physiology of a tumor microenvironment impede intra-tumoral penetration of chemotherapeutic agents. A novel iRGD peptide that exploits the tumor microenvironment can activate integrin-dependent binding to tumor vasculatures and neuropilin-1 (NRP-1)-dependent transport to tumor tissues. Recent studies have focused on its dual-targeting ability to achieve enhanced penetration of chemotherapeutics for the efficient eradication of cancer cells. Both the covalent conjugation and the co-administration of iRGD with chemotherapeutic agents and engineered delivery vehicles have been explored. Interestingly, the iRGD-mediated drug delivery also enhances penetration through the blood-brain barrier (BBB). Recent studies have shown its synergistic effect with BBB disruptive techniques. The efficacy of immunotherapy involving immune checkpoint blockades has also been amplified by using iRGD as a targeting moiety. In this review, we presented the recent advances in iRGD technology, focusing on cancer treatment modalities, including the current clinical trials using iRGD. The iRGD-mediated nano-carrier system could serve as a promising strategy in drug delivery to the deeper tumor regions, and be combined with various therapeutic interventions due to its novel targeting ability.DEAD-Box Helicase 4 (Ddx4)+ ovarian stem cells are able to differentiate into several cell types under appropriate stimuli. Ddx4 expression has been correlated with poor prognosis of serous ovarian cancer (OC), while the potential role of Ddx4+ cells in non-serous epithelial OC (NS-EOC) is almost unexplored. The aim of this study was to demonstrate the presence of Ddx4+ cells in NS-EOC and investigate the effect of follicle-stimulating hormone (FSH) on this population. Increased Ddx4 expression was demonstrated in samples from patients with advanced NS-EOC, compared to those with early-stage disease. Under FSH stimulation, OC-derived Ddx4+ cells differentiated into mesenchymal-like (ML) cells, able to deregulate genes involved in cell migration, invasiveness, stemness and chemoresistance in A2780 OC cells. This effect was primarily induced by ML-cells deriving from advanced NS-EOC, suggesting that a tumor-conditioned germ cell niche inhabits its microenvironment and is able to modulate, in a paracrine manner, tumor cell behavior through transcriptome modulation.Claspin is a multifunctional protein that participates in physiological processes essential for cell homeostasis that are often defective in cancer, namely due to genetic changes. It is conceivable that Claspin gene (CLSPN) alterations may contribute to cancer development. Therefore, CLSPN germline alterations were characterized in sporadic and familial breast cancer and glioma samples, as well as in six cancer cell lines. Their association to cancer susceptibility and functional impact were investigated. Eight variants were identified (c.-68C&gt;T, c.17G&gt;A, c.1574A&gt;G, c.2230T&gt;C, c.2028+16G&gt;A, c.3595-3597del, and c.3839C&gt;T). CLSPN c.1574A&gt;G (p.Asn525Ser) was significantly associated with breast cancer and was shown to cause partial exon skipping and decreased Claspin expression and Chk1 activation in a minigene splicing assay and in signalling experiments, respectively. CLSPN c.2028+16G&gt;A was significantly associated with familial breast cancer and glioma, whereas c.2230T&gt;C (p.Ser744Pro), was exclusively detected in breast cancer and glioma patients, but not in healthy controls. The remaining variants lacked a significant association with cancer. Nevertheless, the c.-68C&gt;T promoter variant increased transcriptional activity in a luciferase assay. In conclusion, some of the CLSPN variants identified in the present study appear to modulate Claspin's function by altering CLSPN transcription and RNA processing, as well as Chk1 activation.The majority of breast cancer specific deaths in women with estrogen receptor positive (ER+) tumors occur due to metastases that are resistant to therapy. There is a critical need for novel therapeutic approaches to achieve tumor regression and/or maintain therapy responsiveness in metastatic ER+ tumors. The objective of this study was to elucidate the role of metabolic pathways that undermine therapy efficacy in ER+ breast cancers. Our previous studies identified Exportin 1 (XPO1), a nuclear export protein, as an important player in endocrine resistance progression and showed that combining selinexor (SEL), an FDA-approved XPO1 antagonist, synergized with endocrine agents and provided sustained tumor regression. In the current study, using a combination of transcriptomics, metabolomics and metabolic flux experiments, we identified certain mitochondrial pathways to be upregulated during endocrine resistance. When endocrine resistant cells were treated with single agents in media conditions that mimic a nutrient deprived tumor microenvironment, their glutamine dependence for continuation of mitochondrial respiration increased. The effect of glutamine was dependent on conversion of the glutamine to glutamate, and generation of NAD+. PGC1α, a key regulator of metabolism, was the main driver of the rewired metabolic phenotype. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine resistant breast tumors is novel, and our findings reveal a critical role that ERα-XPO1 crosstalk plays in reducing cancer recurrences. Combining SEL with current therapies used in clinical management of ER+ metastatic breast cancer shows promise for treating and keeping these cancers responsive to therapies in already metastasized patients.Studies of relationships between eating frequency and/or timing and energy intake have not examined associations with low-calorie sweeteners (LCS). We assessed the frequency of eating behavior related to LCS consumption emphasizing timing, calorie intake, and body mass index (BMI) among United States (US) adults aged ≥19 years. Using the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we defined eating episodes as food and/or beverage intake within 15 min of one another over the first 24-h dietary recall. We coded items ingested during episodes (n = 136,938) and assessed LCS presence using US Department of Agriculture (USDA) food files. Episode analysis found intakes of foods only (27.4%), beverages only (29.5%), and foods with beverages (43.0%). LCS items were consumed without concurrent calories from other sources in fewer than 2.7% of all episodes. Within participants having normal weight (29.4%), overweight (33.6%) and obese (37.1%) BMIs, LCS consumers (35.2% overall) evidenced more episodes/day; and fewer calories, carbohydrates, fats, and protein per episode. Per person, those consuming LCS had lower total calories and higher fiber intake per day. LCS consumption was associated with higher BMI. Number of eating episodes/day and longer hours when eating episodes occurred were also consistently associated with higher BMI. Consuming LCS did not modify these relationships. These results did not show that LCS consumption was associated with increased caloric intake from other dietary sources.This study aimed to develop a physical education fitness program for adolescents to counteract the declining physical activity levels caused by the COVID-19 pandemic, as well as to investigate the program's effect. This mixed-methods study developed and implemented a five-component "Music Beeps" (MB) program to promote adolescents' physical fitness. A total of 240 students from two high schools in South Korea-divided into experimental and control groups-participated in 32 sessions over 16 weeks. The changes in students' fitness were analyzed, and the educational effects were examined via inductive analysis of the observation logs and group and in-depth interviews. The results demonstrated that, whereas the comparison group demonstrated no statistically significant changes in power, muscular strength and endurance, or cardiopulmonary endurance, the experimental group showed changes in all these variables, along with changes in flexibility. Further, the MB program had significant educational effects. First, students reported that musical cues enhanced their fitness motivation and sense of responsibility.