Highest Synergistic Effect Research Articles

Developing a sensitive electrochemical platform constructed with nanoparticles of dysprosium supported on graphene nanoplatelets for the determination of yohimbine

Yohimbine, an α2-adrenoceptor antagonist, is used in the treatment of erectile dysfunction. However, it has various side effects such as tachycardia, arrhythmias, hypertension, dizziness, and poisoning. Some of its side effects are also manifested as anxiety, headaches and increased urinary output. Considering the consumption of yohimbine with dietary supplements and its side effects on the human system, the development of a novel, simple and sensitive method for the determination of yohimbine is significant. For this purpose, an electrochemical method was developed on a glassy carbon electrode (GCE) modified with dysprosium oxide (Dy2O3) and graphene nanoplatelets (GRNP). The electrochemical platform (GCE/GRNP@Dy2O3) possessed high electro-active surface area and lower value of charge transfer resistance (Rct). Yohimbine undergoes irreversible oxidation through a diffusion-controlled process. The observation of improved voltammetric behavior and enhanced peak response for yohimbine at GCE/GRNP@Dy2O3 could be attributed to the high synergistic effect between Dy2O3 and GRNP in addition to the increased surface area and electrocatalytic activity. The expected sensing mechanism of GCE/GRNP@Dy2O3 towards yohimbine might be attributed to the surface oxygen vacancies of Dy2O3 which are available on the surface of the nanocomposite. The oxygen atoms can interact with the functional groups of yohimbine and facilitate the oxidation of yohimbine. The peak response and concentration were found to be correlated over a range of 8.0 × 10−9–7.8 × 10−7 M. The GCE/GRNP@Dy2O3 system exhibited a detection limit (LOD) of 5.7 × 10−9 M for yohimbine. Average recovery values of 98.0 %–104.9 % with lower RSD values in yohimbine supplements and 101.0 %–103.0 % in artificial urine confirmed that GCE/GRNP@Dy2O3 provides reliable results for the determination of yohimbine.

CuOx supported LaCoO3 perovskite for the photoassisted reverse water gas shift reaction at low temperature

CuOx/LaCoO3 systems have been studied for the rWGS reaction under thermal assisted photocatalytic conditions within low temperature range of 180–330 ºC. CuOx species deposited from chemical reduction method over LaCoO3 homogeneously covered the perovskite surface. The reduction pretreatment before reaction leads to the partial Co reduction and the complete reduction of Cu. A significant improvement on CO production has been attained upon Cu incorporation. In addition, upon UV–vis irradiation the CO production is also enhanced. Best results have been obtained for 5 wt% Cu. The highest synergistic effect was observed for the lowest temperature, for which catalytic contribution is negligible. Thus, a good compromise is attained at 300 ºC for which a CO production of 5.45 mmol/h·g and 92 % selectivity, showing a good synergistic effect between thermo and thermo-photocatalytic activity.

Unprecedented electrochemical activity of GdCoO3-gC3N4 nanocomposite for bifunctional oxygen and hydrogen evolution reaction

Development of highly competent and stable electrocatalysts for electrochemical water splitting to attain oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is highly desired. Here in present work, gadolinium cobalt oxide (GdCoO3), graphitized carbon nitride (gC3N4), and their composite is fabricated via hydrothermal method, and then used as electrocatalysts for OER and HER. The prepared electrocatalysts underwent rigorous characterization using X-ray diffraction (XRD) to unravel their structural composition. To further unravel their morphological and textural aspects, scanning electron microscopy (SEM) and Brunauer–Emmett–Teller (BET) techniques were employed. Intriguingly, the synergy of nanoparticles GdCoO3 anchored onto thin nanosheets of gC3N4 exhibited a remarkable surge in OER and HER activities in a 1.0 M KOH electrolyte solution. The composite material showed a remarkable reduction in onset potential of 0.95 V vs Ag/AgCl for OER. On the other hand, impressively it shows the low overpotentials of 210 mV at 10 mA cm−2 with a tafel slope of 44 mV dec−1. Notably, for HER the nanocomposite requires an onset potential of 0.01 V vs Ag/AgCl and 230 mV overpotential to achieve a current density of 10 mA cm−2. The enhanced results are due to that the GdCoO3 nanoparticles integrated onto the nanosheets of gC3N4 shows high surface area and synergistic effect exhibited, which displayed good stability, and are useful for commercial applications. Thus, the exceptional OER performance of the composite combined with its good electrochemical properties, positions it as a viable option for large-scale and sustainable water splitting technologies.

PH-sensitive polymeric micelles enhance the co-delivery of doxorubicin and docetaxel: an emerging modality for treating breast cancer

BackgroundDesigning and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor.MethodsDOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX).ResultsThe final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination.ConclusionsThese findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response.Graphical

Concurrent Subcellular Delivery of Hydrogen Sulfide and a Payload with Near-Infrared Light.

Hydrogen sulfide (H2S) is a gaseous signaling molecule, exerting crucial regulatory functions in organelles and cellular environments. H2S exhibits high therapeutic potential and synergistic effects with other drugs, and its potency is notably enhanced through organelle-specific targeting. Yet, the navigation of light-activated H2S donors to specific organelles remains absent. Here, we report the first organelle-specific photocage that simultaneously delivers H2S and a payload with subcellular precision to mitochondria of live human cells using tissue-penetrating near-infrared light as a trigger. The fluorogenic payload enables real-time monitoring of the process, and we demonstrate the concurrent uncaging in mitochondria through a combination of fluorescence microscopy and mitochondria-specific fluorescent probes. We anticipate that these photocages will permit the precise delivery of H2S-drug combinations with exceptional spatiotemporal control, thereby driving the harnessing of known synergistic effects and the discovery of novel therapeutic strategies.

Combination of Nicotinamide and Agastache rugosa Extract: A Potent Strategy for Protecting Hs68 Cells from UVB-Induced Photoaging.

This study investigated the protective effects of nicotinamide (NAM) and Agastache rugosa extract (AR) against ultraviolet B (UVB)-induced photoaging in Hs68 cells. The results demonstrated that NAM and AR, alone or in combination, exhibited concentration-dependent protective effects against UVB radiation. The highest synergistic effect was observed at a NAM:AR ratio of 6:4. This combination exhibited a synergistic protective effect against UVB-induced photoaging. The sample concentration required for 80% cell survival was 9.70 μM and 131.16 ppm for NAM and AR, respectively. However, when combined, they exhibited strong synergistic effects with concentrations as low as 0.11 μM and 17.50 ppm. Moreover, 5.26 μM of NAM and 1,082.13 ppm of AR were required to inhibit 30% of reactive oxygen species, but the combination treatment required 0.62 μM and 95.49 ppm, respectively. This combination significantly reduced the production of matrix metalloproteinase and increased collagen production. These findings highlight the potential of combining NAM and AR as functional cosmetic materials to protect against UVB-induced photoaging. The synergistic effects observed in this study provide valuable information for developing novel strategies for cosmetic combinations that target UVB-mediated skin damage.

In vitro interactions of combinations of colistin with meropenem, rifampicin and tigecycline in colistin-resistant, biofilm-forming Klebsiella pneumoniae

In this study, it was aimed to reveal the in vitro interactions of combinations of colistin with meropenem, rifampicin and tigecycline in colistin-resistant, biofilm-forming Klebsiella pneumonia. A total of 30 isolates, 15 of which formed biofilms and 15 did not form biofilms, were randomly selected from K. pneumoniae isolates growing in blood samples. The synergy rates of colistin-meropenem, colistin-tigecycline, colistin-rifampicin combinations in planktonic/sessile bacteria are; It was determined as 83,3%/73,3%, 66,6%/33,3%, 100%/60% respectively. Biofilm inhibitory concentration (BIC) of colistin, meropenem, tigecycline, and rifampicin significantly increased after biofilm formation. The synergistic activity seen in the sessile form was independent of the planktonic form. Although a high synergistic effect was observed in the meropenem-colistin combination on sessile bacteria, colistin had very high BIC ​​in all combinations. Large-scale studies are needed in which the number of isolates studied is large, bacterial resistance profiles are evaluated genomically, and various antimicrobial groups are included.

Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate

BackgroundMultidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate.MethodsStandard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate.ResultsOut of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents.ConclusionFortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.

Tetracycline degradation by dual-frequency ultrasound combined with peroxymonosulfate

Tetracycline has received a great deal of interest for the harmful effects of substance abuse on ecosystems and humanity. The effects of different processes on the degradation of tetracycline were compared, with dual-frequency ultrasound (DFUS) in combination with peroxymonosulfate (PMS) being the most effective for the tetracycline degradation. Free radical scavenging experiments showed that O2∙-,SO4∙- and •OH were the main reactive radicals in the degradation of tetracycline. According to the major intermediates of tetracycline degradation identified, three possible degradation pathways were proposed, which are of significance for translational studies of tetracycline degradation. Notably, these intermediates were found to be significantly less toxicity. The number of active bubbles in the degradation vessel was calculated using a semi-empirical formula, and a higher value of 1.44 × 108 L-1s−1 of bubbles was obtained when using dual-frequency ultrasound at 20 kHz (210 W/L) and 80 kHz (85.4 W/L). Therefore, compared to 20 kHz, although the yield of strong oxidizing substances from individual active bubbles decreased slightly, a significant increment of the number of active bubbles still resulted in a higher synergistic effect, and the combination of DFUS and PMS should be effective in promoting the generation of reactive free radicals and mass transfer processes within the degradation vessel, which provides a method for efficient removal of tetracycline from wastewater.

Highly dispersed nickel-tuned silica lanthana catalyst: Interplay of morphology and textural properties for hydrogen-rich syngas through the carbon dioxide reforming of methane

Methane (CH4) and carbon dioxide (CO2) are major contributors to the rise in greenhouse gas emissions, exacerbating global warming. Consequently, it is crucial to convert and utilize these gases effectively to mitigate their impact on the atmosphere. Carbon dioxide (dry) reforming of methane (DRM) offers an efficient solution for converting CH4 and CO2 into syngas (H2/CO). In this study, we compare the effectiveness of a robust catalytic system, including a fibrous silica lanthana-supported nickel (NSLF-10) catalyst, to a silica lanthana-supported nickel composite (NSL-C) developed using commercial lanthana and silica. Our investigation focuses on their respective performances in the production of hydrogen-rich syngas through DRM. The NSLF-10 catalyst exhibited improved physicochemical properties such as uniformly dispersed nickel, stronger metal-support interaction, small nickel particle size, and increased surface area, which significantly enhanced the catalytic performance of DRM. Notably, the NSLF-10 catalyst achieved a high conversion of CH4 and CO2 at 85 % and 83 %, respectively, with an elevated H2/CO ratio compared to the NSL-C catalyst, which has a conversion of CH4 and CO2 at 72 % and 64 %, respectively. The unique properties of the NSLF-10 catalyst provide a high synergistic effect between the nickel active sites and SLF support, leading to a high conversion of CH4 and CO2 with no signs of catalytic deactivation.

ZnO-CeO2 Hollow Nanospheres for Selective Determination of Dopamine and Uric Acid.

ZnO-CeO2 hollow nanospheres have been successfully synthesized via the hard templating method, in which CeO2 is used as the support skeleton to avoid ZnO agglomeration. The synthesized ZnO-CeO2 hollow nanospheres possess a large electrochemically active area and high electron transfer owing to the high specific surface area and synergistic effect of ZnO and CeO2. Due to the above advantages, the resulting ZnO-CeO2 hollow spheres display high sensitivities of 1122.86 μA mM-1 cm-2 and 908.53 μA mM-1 cm-2 under a neutral environment for the selective detection of dopamine and uric acid. The constructed electrochemical sensor shows excellent selectivity, stability and recovery for the selective analysis of dopamine and uric acid in actual samples. This study provides a valuable strategy for the synthesis of ZnO-CeO2 hollow nanospheres via the hard templating method as electrocatalysts for the selective detection of dopamine and uric acid.

Machine learning and IoT Based Robotic Solution for Home Wrist Rehabilitation through Motion Capture Enabled Architecture

The present study investigates the effectiveness of an integrated approach that combines machine learning, robotic rehabilitation, and traditional methods for wrist rehabilitation among the hemiparesis population. Subjects with robotic rehabilitation at the four-week intervention period showed the ball’s significant difference in the flexion and extension angles and demonstrated the better overall outcomes from the robotic intervention . The machine learning models, in particular, the artificial neural networks, provided the prediction of rehabilitation outcomes and demonstrated the high accuracy, high precision, high recall, and high F1 score. This study supports the idea of the beneficial effects of combining robotic rehabilitation with machine learning algorithms and supports the notion that the two benefits could bring high synergistic effects above their individual potentials. The report also contributes to the development of the rehabilitation science of wrists, given that few studies have explored the applications of artificial intelligence methods or robotic rehabilitation beyond the context of feasibility reports. The findings of the current research could contribute useful insights for the decision-making practices of therapists and healthcare providers, also given the reliance on large data contributed by the previous interventions. Future study could investigate the long-term results, the cost-effectiveness of the approaches, and assist in developing the potential results of customization for individual patients.

In Vitro Analysis of Antimalarial Activity of Achillea fragrantissima (Forssk.) Sch.Bip Extracts Based on Beta-Hematin Formation

Introduction: The use of medicinal plants from traditional knowledge systems has increased in recent years. Achillea fragrantissima-infused water has a historical use in relieving gastrointestinal complaints and treating skin inflammations. With the rising resistance to antimalarial drugs, finding safe and affordable new drugs is crucial. Exploring medicinal plants shows promise for drug development in the fight against malaria. Methods: The objective of this research is to examine the in vitro antimalarial activity of A. fragrantissima-infused water, as well as water-ethanol extracts of its leaves, flowers, and stems based on β-hematin formation. Colorimetric semiquantitative assessments based on β-hematin inhibition and evaluation of optical density at 405 nm were employed. Results: The results demonstrated promising antimalarial activity of the different plant parts. The aqueous flower extract exhibited strong activity, comparable to that of the positive control. The leaves extract also showed strong antimalarial activity. The stem's aqueous and ethanolic extracts exhibited lower inhibitory activity compared to flowers and leaves. Synergistic antimalarial activity was observed when mixing the stem and leaves water extracts, as well as when mixing each of the stem and leaves extracts with the flower extract. The highest synergistic effect was observed when all three parts of the plant were mixed, resulting in activity comparable to the positive control. The high-performance liquid chromatography photodiode array (HPLC-PDA) chromatographic method confirmed the presence of rutin in the leaves extract. Conclusion: The findings of this study highlight the potential antimalarial activity of A. fragrantissima. The aqueous flower extract and leaves extract exhibited strong antimalarial activity, while the stem extracts showed relatively lower activity. Furthermore, synergistic effects were observed when combining different parts of the plant. These results suggest that A. fragrantissima holds promise as a potential source for the development of new antimalarial drugs. The confirmation of rutin presence in the leaves extract through HPLC-PDA analysis provides additional insights into the plant's chemical composition.

Abstract 6509: GT0486, a novel mTORC1/2 dual inhibitor, exhibits synergistic antitumor efficacy in combination with BTK inhibitors

Abstract Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is the central signal molecule in regulating cell growth, metabolism, angiogenesis, and survival. The first generation of mTOR inhibitors specifically inhibit mTORC1 but are insensitive to mTORC2 and cannot eliminate the downstream signaling cascade in cancer. GT0486, a second-generation mTORC1/2 dual inhibitor, can selectively suppress mTOR kinase activity while has no inhibitory effect on other kinase receptors. We investigate the anti-tumor efficacy of GT0486 in a variety of tumor cells and xenograft animal models in vitro and in vivo. The combination effects of GT0486 and BTKi (BTK inhibitor) were also evaluated. Compared with other mTOR inhibitors (GDC-0349, AZD-2014, Rapamycin, GDC-0941, and CC-223), GT0486 exhibits the stronger inhibitory activity on human tumor cells, such as U87(glioma), PC-3(prostate cancer), MDA-MB-468(breast cancer) and Huh-7(liver cancer). In B-cell lymphoma, compared with the CC-223, GT0486 shows greater inhibitory potency against TMD8, DoHH2 and WSU-DLCL2, with IC50 values of 85nM, 96nM and 83nM, respectively. Moreover, in the U87 and the PC-3 xenograft animal models, GT0486 strongly reduced tumor growth in dose dependent manner. High synergistic effects were observed with GT0486 in combination with BTK inhibitors, including Acalabrutinib, Ibrutinib, Zanubrutinib and Orelabrutinib in the BTKi sensitive TMD8 cells. In BTKi resistant DoHH2 cells, GT0486 also enhanced the drug sensitivity of BTKi. The possible biomarkers on the synergistic mechanism were further studied. GT0486 improves the role of BTKi on cell cycle arrest in phase G1. At the same time, the phosphorylation levels of mTOR downstream effectors AKT, 4EBP1 and S6 were dose-dependently downregulated after GT0486 treatment, and a significant reduction were observed when combined with BTKi. These results demonstrate that GT0486 is a promising dual mTOR1/2 inhibitor, which is currently undergoing clinical phase I study in China for the treatment of solid tumors. Strong synergistic effects observed with GT0486 in combination with BTKi in this study might open a way for a novel treatment strategy in clinical trials. Citation Format: Xiaodan Hou, Honghua Yan, Xin Zhang, Weidong Qian, Dong Chen, Zhihua Ren, Youzhi Tong. GT0486, a novel mTORC1/2 dual inhibitor, exhibits synergistic antitumor efficacy in combination with BTK inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6509.

FeNiCo|MnGaOx Heterostructure Nanoparticles as Bifunctional Electrocatalyst for Zn-Air Batteries.

Driven by the pressing demand for stable energy systems, zinc-air batteries (ZABs) have emerged as crucial energy storage solutions. However, the quest for cost-effective catalysts to enhance vital oxygen evolution and reduction reactions remains challenging. FeNiCo|MnGaOx heterostructure nanoparticles on carbon nanotubes (CNTs) are synthesized using liquid-phase reduction and H2 calcination approach. Compared to its component, such FeNiCo|MnGaOx/CNT shows a high synergistic effect, low impedance, and modulated electronic structure, leading to a superior bifunctional catalytic performance with an overpotential of 255mV at 10mAcm-2 and half-wave potential of 0.824V (ω=1600rpm and 0.1m KOH electrolyte). Moreover, ZABs based on FeNiCo|MnGaOx/CNT demonstrate notable features, including a peak power density of 136.1mWcm-2, a high specific capacity of 808.3mAhgZn -1, and outstanding stability throughout >158h of uninterrupted charge-discharge cycling. Theoretical calculations reveal that the non-homogeneous interface can introduce more carriers and altered electronic structures to refine intermediate adsorption reactions, especially promoting O* formation, thereby enhancing electrocatalytic performance. This work demonstrates the importance of heterostructure interfacial modulation of electronic structure and enhancement of adsorption capacity in promoting the implementation of OER/ORR, ZABs, and related applications.

Impact of chitosan-incorporated toothpaste on roughness, gloss, and antifungal potential of acrylic resin

This study aimed to test the efficacy of different silica-based toothpastes with or without chitosan, as a method of cleaning the acrylic surfaces of denture prostheses. Acrylic resin specimens were prepared to evaluate surface roughness and gloss (n = 10), and Candida albicans adhesion/inhibition (n = 2). Two toothpastes with different degrees of abrasiveness were used: Colgate (CT) and Elmex (EX), with or without 0.5% chitosan (Ch) microparticles (CTCh or EXCh, respectively). The negative control was brushed with distilled water. Brushing was simulated with a machine. Surface roughness and gloss were analyzed before and after brushing. Candida albicans incidence/inhibition was tested qualitatively to determine the acrylic resin antifungal activity. The roughness and gloss data were analyzed with a generalized linear model, and the Kruskal Wallis and Dunn tests, respectively (α = 5%). Brushing with toothpastes increased roughness and reduced gloss, compared with the negative control (p < 0.05). CT showed a more significantly different change in roughness and gloss, in relation to the other groups (p < 0.05). Addition of chitosan to CT reduced its abrasive potential, and yielded results similar to those of EX and EXCh. Specimens brushed with CT showed a higher potential for Candida albicans adherence, despite its higher antifungal action. Addition of chitosan to the toothpaste made both toothpaste and brushing more effective in inhibiting Candida albicans. CT had the potential to increase roughness, reduce gloss, and increase Candida albicans adherence. In contrast, chitosan added to CT showed greater antifungal potential, and a higher synergistic effect than EX.

Synergistic Effect of CK2 Inhibitor CX-4945 with HDACi Chidamide on Cell Proliferation Arrest and Apoptosis in Acute Myeloid Leukemia

Background CX-4945 is an ATP-competitive inhibitor of CK2, which is currently being used in clinical trials to treat various cancer types. Chidamide (CHI), a novel histone deacetylase inhibitor (HDACi), is now involved in the salvage treatment of relapsed/refractory acute myeloid leukemia (AML) in a clinical trial. The anti-leukemia effects of either single drug have been reported by inducing cell apoptosis through suppressing multi-oncogenic pathways in human tumor cells. However, whether and how the combination of the two drugs exerts synergistic anti-tumor effects remains undetermined. This study is to investigate the synergistic therapeutic effects of CX-4945 in combination with CHI in AML. Methods Cell Counting Kit-8 (CCK-8) cell proliferation assay, Annexin V apoptosis assay, and Propidium Iodide cell cycle assay were performed in AML cells in the presence of CX-4945 only, CHI only, CX-4945 + CHI, and vehicle control for 48h. RNA-seq was performed in U937 cells treated with CX-4945 and CHI, respectively; the differentially expressed genes (DEGs) were identified by R studio, and pathway enrichment of the DEGs was analyzed with Metascape online tool. Data were expressed as the mean ± standard deviation. Ordinary one-way ANOVA statistical analysis and Log-rank test was employed to determine the significant difference between groups. A synergistic effect was determined by the combination indices (CIs) with CalcuSyn software. Results The 50% inhibiting concentration (IC50) of CX-4945 on the U937 and THP-1 cell proliferation is 7.435±0.066μmol/L and 6.787±0.153μmol/L. The IC50 of CHI on the U937 and THP-1 cell proliferation is 3.009±0.32μmol/L and 3.782±0.239μmol/L, respectively. The combination of various doses of CHI with either IC50 or 1/2 IC50 of CX-4945 significantly decreases the cell viability of the cells versus single-drug control and CalcuSyn analysis showed the high synergistic therapeutic effects of CHI with CX-4945 (Fig.1A). The combination of (4µM) CHI with (8µM) CX-4945 significantly induced the G0/G1 cell cycle arrest (p &amp;lt;0.001, Fig.1B) and elevated the % of apoptotic cells (p &amp;lt;0.0001, Fig.1C) in the AML cells compared to either single drug alone. Moreover, the combination of (1.6µM) CHI with (8µM) CX-4945 significantly increased the % of apoptotic cells in the primary blasts from the AML patient versus either single drug alone (p&amp;lt;0.0001, Fig.1D). To further understand the underlying mechanism of the synergy, RNA-seq analysis was performed in U937 cells treated with either CHI or CX-4945, respectively (Fig.2A). The DEGs are achieved upon either drug treatment, and the 76 up-regulated and 411 down-regulated overlapped DEGs were identified (Fig.2B). Pathways analysis showed that the overlapped DEGs are enriched in cell cycle progress, apoptosis, and multiple oncogenic signaling including cMyc and PI3K/AKT signaling pathways (Fig.2C). cMyc and PI3K/AKT-dependent signaling pathways are involved in myeloid cell proliferation. Also, our ChIP-seq data indicated obvious Ikaros binding peaks in the promoter region of cMyc and PIK3CD and they are the direct targets of Ikaros (data not shown). cMyc and PIK3CD are at the top of the overlapped DEGs, indicating the critical roles of the cMyc and PIK3CD underlying the mechanism of the combination in AML. Indeed, the mRNA level of cMyc and PIK3CD is significantly down-regulated upon the combination treatment versus single drug control (Fig.2D or data not shown). Consistently, the mRNA level of PIK3CD is significantly higher expressed in AML patients versus that in bone marrow samples of the healthy donors (p&amp;lt;0.05, Fig.2E) and the AML patients with high PIK3CD high expression have shorter OS than that with low expression (p &amp;lt;0.05, Fig.2F). These data support the hypothesis that the combination exerts the anti-tumor effect by suppression of cMyc and PIK3CD expression in AML. Conclusions The combination of CHI and CX-4945 has a synergistic effect on cell proliferation arrest, apoptosis, and cell cycle arrest by suppressing cMyc and PI3K signaling in AML cells. Our data provide experimental evidence for the combination as a potential option for AML therapy. More pre-clinical studies will be explored for future clinical trials.

Efficient catalytic degradation of VOCs using Mn-based hydrotalcite-like compounds coupled with non-thermal plasma

Aiming to discover a novel catalyst that exhibits a high synergistic effect with plasma technology for the degradation of volatile organic compounds (VOCs), we employed manganese-based layered double hydroxides (LDHs), which are referred to as MMn-LDHs (M=Ni, Co, Fe). Comprehensive physicochemical characterization via catalyst characterization techniques such as XRD, SEM, XPS, BET, confirmed the successful synthesis of the catalysts. These analyses revealed excellent crystallinity, distinctive lamellar structure, and remarkable thermal stability for three synthesized catalysts. The experimental results demonstrate that post non-thermal plasma (post-NTP) catalytic system has significantly improved the degradation efficiency, CO2 selectivity, and carbon balance for toluene, while notably suppressing the formation of by-products (e.g., NOx and O3) compared to the NTP alone system. Among the three MMn-LDHs, NiMn-LDHs exhibited the best performance in the post-NTP-catalytic system, achieving a toluene degradation rate of 95.87%, a CO2 selectivity of 57.41%, a carbon balance of 79.86%, and an energy efficiency of 3.19 g·kWh−1 at a specific energy density (SED) of 930.45 J/L. The catalytic degradation mechanism of toluene was proposed based on a combination of catalyst characterization techniques, plasma emission spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The findings revealed that plasma discharge generated a substantial amount of free radicals and active species, thereby promoting the decomposition of toluene. Subsequently, the residual toluene and intermediate products were adsorbed onto the catalysts, where they underwent further reacted with the abundant hydroxyl radicals and activate metal species on the catalyst surface, ultimately decomposing into CO2 and H2O. Additionally, the interaction of ozone with LDHs facilitated the generation of reactive oxygen species, consequently accelerating the decomposition of organic intermediates, formation of CO2, and the enhancement of toluene mineralization. The finding in this work offer valuable theoretical support for the plasma-catalytic degradation of VOCs.

Synergistic antifungal activity and potential mechanism of action of a glycolipid like compound produced by Streptomyces blastmyceticus S108 against Candida clinical isolates.

The present study aimed to investigate a novel antifungal compound produced by Streptomyces blastmyceticus S108 strain. Its effectiveness against clinical isolates of Candida species and its synergistic effect with conventional antifungal drugs were assessed and its molecular mechanism of action was further studied against C. albicans. A newly isolated strain from Tunisian soil, Streptomyces blastmyceticus S108, showed significant antifungal activity against Candida species by well diffusion method. The butanolic extract of S108 strain supernatant exhibited the best anti-Candida activity with a minimal inhibitory concentration (MIC) value of 250 μg mL-1, determined by the microdilution method. The bio-guided purification steps of the butanolic extract were performed by chromatographic techniques. Among the fractions obtained, F13 demonstrated the highest level of activity, displaying a MIC of 31.25 μg mL-1. Gas Chromatography-Mass Spectrometry (GC-MS) and Electrospray Ionisation Mass Spectrometry (ESI-MS) analyses of this fraction (F13) revealed the glycolipidic nature of the active molecule with a molecular weight of 685.6 m/z. This antifungal metabolite remained stable to physicochemical changes and did not show hemolytic activity even at 4 MIC corresponding to 125 µg mL-1 towards human erythrocytes. Besides, the glycolipid compound was combined with 5-flucytosine and showed a high synergistic effect with a FICI value 0.14 against C. albicans ATCC 10231. This combination resulted in a decrease of MIC values of 5-flucytosine and the glycolipid-like compound by 8 and 64-fold, respectively. The examination of gene expression in treated Candida albicans cells by qPCR revealed that the active compound tested alone or in combination with 5-flucytosine blocks the ergosterol biosynthesis pathway by down regulating the expression of ERG1, ERG3, ERG5, ERG11 and ERG25 genes. The new glycolipid like compound, produced by Streptomyces S108 isolate, could be a promising drug for medical use against pathogenic Candida isolates.

Highly efficient multifunctional mono-component flame retardants comprising of sulfenamide and phosphate moieties for polypropylene

A strategy to enhance flame retardant properties of polypropylene (PP) has been investigated by the design of six multifunctional mono-component flame retardants denoted from NS1 to NS6, where sulfenamide and phosphate moieties have been integrated into a single molecule. Herein, the synthesis and characterization of six different mono-component flame retardants are presented. Thermal decomposition characteristics of the multifunctional flame retardants were studied by thermogravimetry analysis, and a 5% mass lose was recorded in the temperature range between 220 °C to 267 °C for the samples. Moreover, the flame retardant samples were oven aged up to 260 °C in the presence and absence of 9, 10-dihydroantracene and the formed decomposition products were analyzed using GC/MS, LC/MS, 13C NMR and 31P NMR. The results indicate that the sulfenamide bond dissociates before the phosphorus moiety for samples NS1, NS2, NS3 and NS6. Whereas the phosphorus moiety breaks first in case of NS4 and NS5. The prepared flame retardants were then admixed with polypropylene in a Haake Rheocord melt blender at loadings ranging from 0.5 to 4 wt%. Thereafter, polypropylene films and plaques were prepared by hot pressing and their flame retardant properties were evaluated according to DIN 4102-B2 and UL94V standards, respectively. All the PP film samples containing any of the different multifunctional flame retardants at the low loading of 0.5 wt% passed the DIN4102 B2 test and for NS1film sample no burning dripping nor ignition of paper were recorded. Noteworthy, is that NS2 and NS3 samples reached the UL94V2 classification as standalone flame retardants even at a loading of only 4 wt%. From this standpoint, it seems the multifunctional mono-component flame retardants may exhibit inherently an exceptionally high synergistic effect.