Synergistic Combination Research Articles

Unraveling the Electrochemical Insights of Cobalt Oxide/Conducting Polymer Hybrid Materials for Supercapacitor, Battery, and Supercapattery Applications.

This review article focuses on the potential of cobalt oxide composites with conducting polymers, particularly polypyrrole (PPy) and polyaniline (PANI), as advanced electrode materials for supercapacitors, batteries, and supercapatteries. Cobalt oxide, known for its high theoretical capacitance, is limited by poor conductivity and structural degradation during cycling. However, the integration of PPy and PANI has been proven to enhance the electrochemical performance through improved conductivity, increased pseudocapacitive effects, and enhanced structural integrity. This synergistic combination facilitates efficient charge transport and ion diffusion, resulting in improved cycling stability and energy storage capacity. Despite significant progress in synthesis techniques and composite design, challenges such as maintaining structural stability during prolonged cycling and scalability for mass production remain. This review highlights the synthesis methods, latest advancements, and electrochemical performance in cobalt oxide/PPy and cobalt oxide/PANI composites, emphasizing their potential to contribute to the development of next-generation energy storage devices. Further exploration into their application, especially in battery systems, is necessary to fully harness their capabilities and meet the increasing demands of energy storage technologies.

Construction of Heterointerfaced Nanoreactor Electrocatalyst via In Situ Evolution Toward Practical Room‐Temperature Sodium–Sulfur Batteries

AbstractSodium‐sulfur (Na─S) batteries have drawn considerable research interest owing to their high theoretical energy density and nature abundance. However, the intrinsic sluggish kinetics that has so far been scarcely explored in the conversion reaction of sodium polysulfides (NaPS) hinders its practical application. Herein, the design strategy of heterointerfaced nanoreactor is presented as sulfur reduction reaction (SRR) electrocatalyst for room temperature Na─S batteries. The synergistic incorporation of heterointerface and confined structure design can modulate the electronic structure of transitional metal active site and upshift its d‐band center, leading to enhanced NaPS adsorption and catalytic conversion toward streamlined SRR. Moreover, the spatial confinement of nanoreactor can not only stockpile nanoparticles to avoid their agglomeration and detachment, but also effectively immobilize sulfur species to inhibit shuttle effect and accommodate volume expansion over sodiation. The as‐developed electrocatalyst can achieve high discharge capacity of 1310 mAh g−1, remarkable cycling stability over 2500 cycles, and excellent performance under high sulfur loading and lean electrolyte/sulfur ratio. Ah level pouch cell can also exhibit promising performance for practical application. This strategy affords a synergistic combination of nanoreactor and heterointerface structure engineering toward fast and reliable electrochemistry, paving ways for the practical application of room temperature Na─S batteries.

Quality by design-based optimization of teriflunomide and quercetin combinational topical transferosomes for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease. Combination therapy is anticipated to surpass monotherapy by targeting multiple pathways involved in RA progression. The present aim is to develop a combination of Teriflunomide (TFD) and Quercetin (QCN) loaded transferosomal gel to enhance permeability and achieve localized delivery to joint tissues. TFD or QCN transferosomes were optimized employing a 3-level, 3-factorial design Box-Behnken design (BBD). The transferosomes exhibited sustained in-vitro drug release. The topical combination gel underwent thorough evaluation of rheology, and also ex-vivo studies showed enhanced permeability through rat skin. The synergistic combination of TFD and QCN effectively suppressed NO, TNF-α and IL-6 levels in in-vitro RAW 264.7 cells. The cytotoxicity in HaCaT cell lines indicates non-toxicity of the gel, further confirmed by skin irritation study conducted in rats. The in-vivo anti-arthritic activity was evaluated in complete freund’s adjuvant induced rat paw edema model illustrates the effectiveness of the combination transferosomal gel compared to other treatment groups. In conclusion, the topical delivery of TFD and QCN combination transferosomal gel demonstrated anti-arthritic activity through localized delivery whichallows for dose reduction, thereby may reduce the systemic drug exposure and mitigate the side effects associated with oral administration of TFD.

Synergistic oral beta-lactam combinations for treating tuberculosis.

The enormous burden of tuberculosis (TB) worldwide is a major challenge to human health, but the costs and risks associated with novel drug discovery have limited treatment options for patients. Repurposing existing antimicrobial drugs offers a promising avenue to expand TB treatment possibilities. This study aimed to explore the activity and synergy of beta-lactams in combination with a beta-lactamase inhibitor, which have been underutilised in TB treatment to date. Based on inhibitory concentration, oral bioavailability and commercial availability, seven beta-lactams (cefadroxil, tebipenem, cephradine, cephalexin, cefdinir, penicillin V, flucloxacillin), two beta-lactamase inhibitors (avibactam and clavulanate), and three second-line TB drugs (moxifloxacin, levofloxacin and linezolid) were selected for combination in vitro testing against Mycobacterium tuberculosis H37Rv. Resazurin assays and colony forming unit (CFU) enumeration were used to quantify drug efficacy, Chou-Talalay calculations were performed to identify drug synergy and Chou-Martin calculations were performed to quantify drug dose reduction index (DRI). The order of activity of beta-lactams was cefadroxil>tebipenem>cephradine>cephalexin>cefdinir>penicillin V>flucloxacillin. The addition of clavulanate improved beta-lactam activity to a greater degree than the addition of avibactam. As a result, avibactam was excluded from further investigations, which focused on clavulanate. Synergy was demonstrated for cefdinir/cephradine, cefadroxil/tebipenem, cefadroxil/penicillin V, cefadroxil/cefdinir, cephalexin/tebipenem, cephalexin/penicillin V, cephalexin/cefdinir, cephalexin/cephradine and cefadroxil/cephalexin, all with clavulanate. However, combining beta-lactams with moxifloxacin, levofloxacin or linezolid resulted in antagonistic effects, except for the combinations of penicillin V/levofloxacin, penicillin V/moxifloxacin and cefdinir/moxifloxacin. Beta-lactam synergy may provide viable combination therapies for the treatment of TB.

Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.

Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs). The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model. The Severance dataset showed that DRD2 and DRD3 expression was higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model. The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.

Imidazoles and Quaternary Ammonium Compounds as Effective Therapies against (Multidrug-Resistant) Bacterial Wound Infections.

The rise and spread of antimicrobial resistance complicates the treatment of bacterial wound pathogens, further increasing the need for newer, effective therapies. Azoles such as miconazole have shown promise as antibacterial compounds; however, they are currently only used as antifungals. Previous research has shown that combining azoles with quaternary ammonium compounds yields synergistic activity against fungal pathogens, but the effect on bacterial pathogens has not been studied yet. In this study, the focus was on finding active synergistic combinations of imidazoles and quaternary ammonium compounds against (multidrug-resistant) bacterial pathogens through checkerboard assays. Experimental evolution in liquid culture was used to evaluate the possible emergence of resistance against the most active synergistic combination. Several promising synergistic combinations were identified against an array of Gram-positive pathogens: miconazole/domiphen bromide, ketoconazole/domiphen bromide, clotrimazole/domiphen bromide, fluconazole/domiphen bromide and miconazole/benzalkonium chloride. Especially, miconazole with domiphen bromide exhibits potential, as it has activity at a low concentration against a broad range of pathogens and shows an absence of strong resistance development over 11 cycles of evolution. This study provides valuable insight into the possible combinations of imidazoles and quaternary ammonium compounds that could be repurposed for (topical) wound treatment. Miconazole with domiphen bromide shows the highest application potential as a possible future wound therapy. However, further research is needed into the mode of action of these compounds and their efficacy and toxicity in vivo.

A multi-task graph deep learning model to predict drugs combination of synergy and sensitivity scores

BackgroundDrug combination treatments have proven to be a realistic technique for treating challenging diseases such as cancer by enhancing efficacy and mitigating side effects. To achieve the therapeutic goals of these combinations, it is essential to employ multi-targeted drug combinations, which maximize effectiveness and synergistic effects.ResultsThis paper proposes ‘MultiComb’, a multi-task deep learning (MTDL) model designed to simultaneously predict the synergy and sensitivity of drug combinations. The model utilizes a graph convolution network to represent the Simplified Molecular-Input Line-Entry (SMILES) of two drugs, generating their respective features. Also, three fully connected subnetworks extract features of the cancer cell line. These drug and cell line features are then concatenated and processed through an attention mechanism, which outputs two optimized feature representations for the target tasks. The cross-stitch model learns the relationship between these tasks. At last, each learned task feature is fed into fully connected subnetworks to predict the synergy and sensitivity scores.The proposed model is validated using the O’Neil benchmark dataset, which includes 38 unique drugs combined to form 17,901 drug combination pairs and tested across 37 unique cancer cells. The model’s performance is tested using some metrics like mean square error (MSE\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$MSE$$\\end{document}), mean absolute error (MAE\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$MAE$$\\end{document}), coefficient of determination (R2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${R}^{2}$$\\end{document}), Spearman, and Pearson scores. The mean synergy scores of the proposed model are 232.37, 9.59, 0.57, 0.76, and 0.73 for the previous metrics, respectively. Also, the values for mean sensitivity scores are 15.59, 2.74, 0.90, 0.95, and 0.95, respectively.ConclusionThis paper proposes an MTDL model to predict synergy and sensitivity scores for drug combinations targeting specific cancer cell lines. The MTDL model demonstrates superior performance compared to existing approaches, providing better results.

From defense to offense: antimicrobial peptides as promising therapeutics for cancer.

Antimicrobial peptides (AMPs), naturally occurring components of innate immunity, are emerging as a promising new class of anticancer agents. This review explores the potential of AMPs as a novel class of anticancer agents. AMPs, naturally occurring peptides with broad-spectrum antimicrobial activity, exhibit several characteristics that make them attractive candidates for cancer therapy, including selectivity for cancer cells, broad-spectrum activity, and immunomodulatory effects. Analysis of a dataset of AMPs with anticancer activity reveals that their effectiveness is influenced by various structural properties, including net charge, length, Boman index, and hydrophobicity. These properties contribute to their ability to target and disrupt cancer cell membranes, interfere with intracellular processes, and modulate the immune response. The review highlights the promising potential of AMPs as a new frontier in cancer treatment, offering hope for more effective and less toxic therapies. AMPs demonstrate promising potential in cancer therapy through multiple mechanisms, including direct cytotoxicity, immune response modulation, and targeting of the tumor microenvironment, as evidenced by extensive preclinical studies in animal models showing tumor regression, metastasis inhibition, and improved survival rates. AMPs show significant potential as cancer therapeutics through their direct cytotoxicity, immune response modulation, and tumor microenvironment targeting, with promising results from preclinical studies and early-phase clinical trials. Future research should focus on optimizing AMP properties, developing novel delivery strategies, and exploring synergistic combination therapies to fully realize their potential as effective cancer treatments, while addressing challenges related to stability, delivery, and potential toxicity.

Zidovudine in synergistic combination with nitrofurantoin or omadacycline: in vitro and in murine urinary tract or lung infection evaluation against multidrug-resistant Klebsiella pneumoniae.

Limited treatment options and multidrug-resistant (MDR) Klebsiella pneumoniae present a significant therapeutic challenge, underscoring the need for novel approaches. Drug repurposing is a promising tool for augmenting the activity of many antibiotics. This study aimed to identify novel synergistic drug combinations against K. pneumoniae based on drug repurposing. We used the clinically isolated GN 172867 MDR strain of K. pneumoniae to determine the reversal resistance activity of zidovudine (AZT). The combined effects of AZT and various antibiotics, including nitrofurantoin (NIT) and omadacycline (OMC), were examined using the checkerboard method, growth curves, and crystal violet assays to assess biofilms. An in vitro combination activity testing was carried out in 12 isolates of K. pneumoniae. In vivo murine urinary tract and lung infection models were used to evaluate the therapeutic effects of AZT + NIT and AZT + OMC, respectively. The fractional inhibitory concentration index and growth curve demonstrated that AZT synergized with NIT or OMC against K. pneumoniae strains. In addition, AZT + NIT inhibited biofilm formation and cleared mature biofilms. In vivo, compared with untreated GN 172867-infected mice, AZT + NIT and AZT + OMC treatment decreased colony counts in multiple tissues (P < 0.05) and pathological scores in the bladder and kidneys (P < 0.05) and increased the survival rate by 60% (P < 0.05). This study evaluated the combination of AZT and antibiotics to treat drug-resistant K. pneumoniae infections and found novel drug combinations for the treatment of acute urinary tract infections. These findings suggest that AZT may exert significant anti-resistance activity.

Synergistic invitro antimicrobial activity of polyherbal combination of Morinda lucida fruit and Pterocarpus santalinoides seed against multi-drug resistant clinical bacterial isolates

Background: Synergistic drug combination has been shown to be a way of bypassing drug resistance and reducing the amounts of antimicrobials consumed. As infections caused by multi-drug resistant organisms (MDROs) continue to pose global threat, it is important to search for new antimicrobial combinations of plant origin that are safe and readily available. The objective of this study is to evaluate the synergistic antimicrobial activity of extracts of Morinda lucida fruit and Pterocarpus santalinoides seed against multi-drug resistant (MDR) bacterial isolates Methodology: Morinda lucida and P. santalinoides fruits were plucked and washed clean, and the fruits of P. santalinoides were deseeded to remove the seeds. They were cut into smaller pieces and dried under shade before being milled into smooth powder and extracted with methanol. The clinical bacterial isolates used were MDR Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The phytochemical constituents of the extracts were determined using the standard method. The invitro antimicrobial assay of the extracts was done at a concentration of 50 to 400 mg/ml using the agar well diffusion technique. The minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of each extract were determined using the Checker-board micro-titration method, and the FIC result obtained for each isolate was used to calculate the fractional inhibitory concentration index (FICI) of the combined extracts. The time kill assay was performed to confirm the synergistic and bactericidal activities from the MIC values obtained. Results: The phytochemical analysis revealed that the extracts of both herbal plants contained alkaloids, phenol, tannin, saponin, glycosides, and terpenoids. The antimicrobial assay results showed that the polyherbal combination of the extracts was active against all the MDR bacterial isolates tested with varying zones of inhibition. The mean inhibition zone diameters of individual M. lucida and P. santalinoides ranged from 18.0±0.9mm to 26.0±1.4mm and 17.0±0.1mm to 24.0±0.2mm respectively, while the MIC ranged from 6.25mg/ml to 12.5mg/ml for M. lucida and 12.5 mg/ml for P. santalinoides. The mean inhibition zone diameter of the polyherbal combination of the two plant extracts ranged from 25.00±00mm to 34.0±0.4mm, which compared favorably with that of levofloxacin control (28.0±0.0mm to 32.00±0.0mm), while their MIC ranged from 0.39mg/ml to 1.56mg/ml. The FIC of M. lucida extract ranged from 0.06mg/ml to 0.25mg/ml while that of P. santalinoides ranged from 0.03mg/ml to 0.13mg/ml. The FICI of combined extracts ranged from 0.09mg/ml to 0.38 mg/ml for all the MDR isolates, which is less than 0.5mg/ml, indicating synergism against all the isolates. The time of kill assay confirmed the synergistic and bactericidal activities with a 3log10 CFU/ml decrease in the number of viable cells within 6 hours of incubation.Conclusion: Our findings showed synergistic antibacterial actions of extracts of M. lucida fruit and P. santalinoides seed against MDR clinical bacterial isolates, comparable to levofloxacin. Combination of these herbal plants may serve as alternative sources of antimicrobial agents for the treatment of infections caused by MDR bacterial pathogens.

Structural studies and functional validation of Eugenol and Ferulic acid against Enterococcus faecalis Sortase A.

Enterococcus faecalis (E. faecalis) is commonly occurring pathogen associated with nosocomial infections. Infections are difficult to treat because of their multidrug-resistant (MDR) nature and their tendency to form biofilms. Therefore, it is essential to find alternative medicinal approaches of treatment. In this regard, targeting an important protein for drug development can be an alternative approach. Sortase A (SrtA) is an important enzyme involved in anchoring cell surface-exposed proteins to the cell envelope. SrtA is present in Gram-positive bacteria which catalyses the attachment of several virulence factors and other proteins to the cell membrane. It is involved in bacterial pathogenesis, therefore, it's a promising drug target for the development of anti-microbial drugs targeting cell adhesion, evasion, and biofilm development.To identify SrtA potential inhibitors, we havepurified E. faecalis Sortase A (EfSrtAΔN59). Structural studiesalong with molecular docking of protein with selected ligand molecules were done andconfirmed by MD simulation experiments. We have also performed functional validation of these compounds on bacterial growth, anti-biofilm assays and inhibition assay of selected ligands were also done against E. faecalis individually and in synergistic combinations. Results indicated that both Eugenol and Ferulic acid bind to EfSrtAΔN59 with significant interactions and show promising results.

Electrochemical detection of human papillomavirus DNA based on an ultrasensitive electrochemical sensing platform using N-graphene paper

Human papillomavirus (HPV) is the primary cause of cervical cancer, a major global health concern affecting women worldwide. Early detection of high-risk HPV genotypes is crucial for timely intervention and reducing disease burden. However, current detection methods often lack sensitivity, speed, or cost-effectiveness, especially in resource-limited settings. This work addresses this critical need by developing an ultrasensitive electrochemical biosensing platform based on nitrogen-doped graphene paper electrodes for quantifying high-risk HPV16 DNA sequences. The N-graphene nanohybrid, fabricated via simple solvothermal treatment of biomass-derived graphene oxide, demonstrated significantly enhanced electrical and electrocatalytic properties compared to undoped graphene. DNA detection was achieved through characteristic oxidation signals of guanine bases, which displayed a wide linear dynamic range (0.5–100 μg/mL), low detection limit (75 pg/mL), and excellent reproducibility (relative standard deviation <3.5 %). Detailed spectroscopic and electrochemical analyses revealed the key roles of pyridinic nitrogen defects in improving interfacial charge transfer kinetics and mitigating biofouling issues. This synergistic combination of high electrical conductivity and versatile surface functionality paves the way for equipment-free, point-of-care genosensor devices tailored for quantitative biomarker screening in resource-constrained environments.

Modification of gel properties of Meretrix meretrix (clam) with polysaccharides: physical characterization and interaction mechanism.

This study investigated the contribution of 11 polysaccharides (2%, w/w), including pectin (PC), κ-carrageenan (KC), ι-carrageenan (IC), gellan gum (GG), guar gum (GM), sodium alginate (SA), konjac gum (KG), gum arabic (GA), fucoidan (FC), locust bean gum (LBG), and curdlan (CD), to the gel and microstructural properties of Meretrix meretrix clam gel (MMG). The hardness, springiness and chewiness of MMG with KC, IC, GG, SA and FC addition increased by ~10%-250%, while PC, GM, KG and LBG groups decreased by ~0.6% to 69%. KC, IC, SA, GG and FC decreased the cooking loss rate (CLR) by 69.4% to 88.7% and correspondingly enhanced the water holding capacity (WHC) by 10.2% to 21.4%, which was accompanied by an increased bound water and immobilized water area and high hydrogen proton density. The addition of KC transformed the MMG microstructure from a loose network with large pores to a compact, dense network, reducing lacunarity by 57.9%. The primary intermolecular forces in MMG with the incorporation of KC, IC, GG, SA and FC were hydrophobic interactions and disulfide bonds, which increased by 32.8%-105.3% and 45.6%-114.5% than MMG alone, respectively. Collectively, KC, IC, GG, SA and FC could improve the gel properties of MMG and the strongest synergistic combination was found in the MMG/KC system. This study suggests that the incorporation of polysaccharides is a strategy with potential for modifying the gel properties of shellfish surimi products. © 2024 Society of Chemical Industry.

Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment.

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti-tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol-altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment.

Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment

AbstractCholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti‐tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol‐altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment.

Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents.

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients' health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed. Notably, some of the synergistic combinations showed selective toxicity towardmelanoma cells over nontumorigenic human keratinocytes. Furthermore, immunofluorescence experiments highlighted the potential implication of G4 structures in the molecular mechanisms driving the synergistic interaction between some chemotherapeutics and G4 binders. Overall, our systematic study supports the combination of G4-interacting molecules with standard antineoplastic drugs as a promising antitumor strategy.

The Application of Nano Zero-Valent Iron in Synergy with White Rot Fungi in Environmental Pollution Control.

Developing efficient and sustainable pollution control technologies has become a research priority in the context of escalating global environmental pollution. Nano zero-valent iron (nZVI), with its high specific surface area and strong reducing power, demonstrates remarkable performance in pollutant removal. Still, its application is limited by issues such as oxidation, passivation, and particle aggregation. White rot fungi (WRF) possess a unique enzyme system that enables them to degrade a wide range of pollutants effectively, yet they face challenges such as long degradation cycles and low degradation efficiency. Despite the significant role of nZVI in pollutant remediation, most contaminated sites still rely on microbial remediation as a concurrent or ultimate treatment method to achieve remediation goals. The synergistic combination of nZVI and WRF can leverage their respective advantages, thereby enhancing pollution control efficiency. This paper reviews the mechanisms, advantages, and disadvantages of nZVI and WRF in pollution control, lists application examples, and discusses their synergistic application in pollution control, highlighting their potential in pollutant remediation and providing new insights for combined pollutant treatment. However, research on the combined use of nZVI and WRF for pollutant remediation is still relatively scarce, necessitating a deeper understanding of their synergistic potential and further exploration of their cooperative interactions.

Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy

Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.

Enhancing the strength-ductility synergy of dual-phase Al0.3CoCrFeNiTi0.3 high-entropy alloys through the regulation of B2 phase content

In this study, Al0.3CoCrFeNiTi0.3 high-entropy alloys (HEAs) with different phase contents and microstructures were prepared through cold rolling and recrystallization annealing. This method achieved a synergistic combination of strength and ductility, with the CR1000-1 HEA attaining an ultimate tensile strength of 1175 MPa and a uniform elongation of 21.5 %. In Al0.3CoCrFeNiTi0.3, there exist two distinct phase morphologies: dispersed structure and clustered structure. Using in-situ high-resolution digital image correlation at the microscale, it was observed that local strain in the dispersed structure tends to concentrate along the phase boundaries when a small strain is applied. As the applied strain increases, strain rapidly concentrates in the FCC phase and subsequently in the B2 phase. For the clustered structure, the strain initially concentrates rapidly within the B2 phase and then gradually diffuses into the FCC phase. The low degree of inhomogeneity of the dispersed structure reduces the likelihood of stress concentration and the risk of damage initiation. Furthermore, we observed the synergistic strain hardening effect produced by various deformation mechanisms, such as dislocation pile-ups, dislocation networks, interacting stacking faults, and deformation twins. This study provides valuable insights for the fabrication of dual-phase HEAs with enhanced strength-ductility synergy, applicable to a wide range of engineering applications.

Lightweight composite from graphene-coated hollow glass microspheres for microwave absorption

In developing the effective and lightweight materials for microwave absorption, graphene holds a bright promise because of its excellent electrical properties and low density, but it suffers from poor impedance matching; while the hollow glass microspheres on the other hand have extremely low density and are dielectric. Their synergistic combination could achieve a perfect impedance matching and thus create a novel lightweight absorption composite. The metamaterial structure absorber can efficiently absorb electromagnetic waves over a wide frequency range. This study employs a hydrothermal method to deposit graphene onto the surfaces of hollow glass microspheres, followed by the design of a metamaterial absorber. Upon coating with graphene flakes, the composite material effectively dissipates electromagnetic wave energy through mechanisms such as interfacial polarization, dielectric loss, and the multiple scattering effects of hollow glass microspheres and graphene flakes. The composite exhibits an effective absorption bandwidth up to 4.02 GHz under a graphene flakes mass fraction of 30 %. More importantly, the incorporation of the metamaterial absorber design further significantly enhances the absorption bandwidth to 7.7 GHz. This material demonstrates significant advantages in terms of lightweight and broadband absorption performance, providing new insights for the research of high-performance lightweight and wideband absorbing materials in the future. However, further investigation is required to examine its long-term stability and performance in complex environments.