Synergistic Effect In Treatment Research Articles

Novel short Agave americana based biocomposite and nanobiocomposites for automotive applications

Short fibers of Agave Americana (AA) was extracted from its plant leaf, was chemically treated with Ac2O, HCOOH, H2O2, KMnO4 and NaOH, and then characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), thermo-gravimetric/differential thermo-gravimetric (TGA/DTG), and field emission-scanning electron microscopy (FE-SEM). PVA stabilized copper nanoparticles from chemical reduction method was characterized using field emission-scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDAX), powder X-ray diffraction (PXRD), Dynamic light scattering analysis (DLS), UV–visible absorption spectroscopy, Fourier Transform infrared (FT-IR) spectroscopy and Thermogravimetric analysis/differential thermogravimetry (TGA/DTG). Bio-composites (AA + Polyester Resin (PE) and hybrid nano bio-composites (AA + Polyester Resin (PE) + Cu) were prepared from the untreated and treated AA fibers and further characterized. The synergistic effect of chemical treatment on morphological (SEM), thermal (TGA/DTG), mechanical properties (flexural, tensile, impact and compressive strength) followed by % water absorption were examined. The average surface roughness values (Ra) of chemical treated fiber was identified to be in decreasing manner along with compression strength of biocomposite in the order of untreated (10.74 μm, 44.01 MPa) > NaOH (8.55 μm, 45.07 MPa) > HCOOH (3.49 μm, 24.10 MPa) Ac2O (3.24 μm, 22.10 MPa) > H2O2 (2.51um, 17.9 MPa) > KMnO4 (1.52 μm, 15.1 MPa) treated fibers. Subsequently, the addition of 2s@PVA led to reverse the order namely, the compressive strength of the bionanocomposites were Untreated (10.74 μm, 9.0 MPa) < NaOH (8.55 μm, 0.1 MPa) < HCOOH (3.49 μm, 3.6 MPa) < Ac2O (3.24 μm, 7.6 MPa) < H2O2 (2.51um, 13.3 MPa) < KMnO4 (1.52 μm, 44.1 MPa) treated fibers. Similarly, the biocomposite where the fibres were treated with NaOH, HCOOH were more rough and had, good interconnection between fiber/PE matrix along with enhanced mechanical properties. On addition of nanobiocomposite, only KMnO4 treated fiber composite possed significant mechanical properties. Therefore, mixing CuNPs@PVA with KMnO4 treated fibers led to significant boost to the mechanical properties and minimised the % water absorption properties when compared to the untreated AA/PE biocomposites. The KMnO4 treatment of the AA fiber and addition of copper nanoparticles caused the enhancement of thermal properties, tensile strength and flexural strength. But, these nanobiocomposites were observed to have low impact strength; while, H2O2 treated nanobiocomposites had highest impact strength. The chemical treatment of the AA fiber with NaOH, Ac2O and KMnO4 developed the water resistance of the respective biocomposites. All the nanobiocomposites with chemically treated AA fibers (except Ac2O) were found to have high water resistance. So, they can be used in automotive industry for non-structural applications.

Spatiotemporally-controlled hydrophobic drug delivery via photosensitizer-driven assembly-disassembly for enhanced triple-negative breast cancer treatment

Therapeutic approaches for triple-negative breast cancer (TNBC) have been continuously advancing, but inadequate control over release behavior, insufficient tumor selectivity, and limited drug availability continue to impede therapeutic outcomes in nanodrug systems. In this study, we propose a general hydrophobic antineoplastic delivery system, termed spatiotemporally-controlled hydrophobic antineoplastic delivery system (SCHADS) for enhanced TNBC treatment. The key feature of SCHADS is the formation of metastable photosensitive-antineoplastic complexes (PACs) through the self-assembly of hydrophobic drugs driven by photosensitive molecules. With the further decoration of tumor-targeting peptides coupled with the EPR effect, the PACs tend to accumulate in the tumor site tremendously, promoting drug delivery efficiency. Meanwhile, the disassembly behavior of the metastable PACs could be driven by light on demand to achieve in situ drug release, thus promoting chemotherapeutics availability. Furthermore, the abundant ROS generated by the photosensitizer could effectively kill tumor cells, ultimately realizing an effective combination of photodynamic and chemotherapeutic therapy. As an exemplary presentation, chlorin e6 has been chosen to drive the formation of PACs with the system xc− inhibitor sorafenib. Compared with pure drug treatment, the PACs with the above-described preponderances exhibit superior therapeutic effects both in vitro and in vivo and circumvent the side effects due to off-target. By manipulating the laser irradiation, the PACs-treated cell death mechanism could be dynamically regulated, thus providing the potential to remedy intrinsic/acquired resistance of tumor. Collectively, this SCHADS achieves spatio-temporal control of the drug that greatly enhances the availability of anticarcinogen and realizes synergistic antitumor effect in TNBC treatment, even ultimately being extended to the treatment of other types of tumors.

Abstract 3727: Synergistic effect of CD47 blockade and EPHA3 treatment on recurrent head and neck cancers

Abstract CD47 acts as a “don’t eat me “signal and suppresses it through its interaction with signal regulatory protein (SIRP-a) on the macrophage. CD47 is expressed in many human cancer cells, including head and neck cancer. Additionally, we reported in a previous study that EphA3 is overexpressed in radioresistant head and neck cancer and may play an important role in the development of radioresistance in head and neck cancer. In our present study, we demonstrated that the blockade of EPHA3 and CD47 attenuates the function of M2-like macrophages and may contribute to macrophage polarization toward the M1 phenotype. Here, we combined a therapeutic strategy of an anti-EPHA3 and an anti-CD47 antibody. Using mRNA sequencing and fluorescence imaging, we showed that the combination treatment could significantly enhance the effectiveness of anti-EPHA3 and anti-CD47 antibodies, in reactivating macrophages and reversing macrophage polarization. In addition to using flow cytometry in vivo, combination treatments can alter the proportion of tumor-associated macrophages (TAMs). Collectively, our findings suggested that the combination treatment of anti-EphA3 and the anti-CD47 antibodies could significantly improve tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. Citation Format: Song Hee Kim, Myung Woul Han, Ji Won Kim, Seong Who Kim. Synergistic effect of CD47 blockade and EPHA3 treatment on recurrent head and neck cancers [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 3727.

Abstract 5285: DKK1 blockade inhibits progression of bone metastases via multiple mechanisms and synergize with zoledronate treatment

Abstract Background: Despite the important breakthroughs of immune checkpoint blockade (ICB) therapy in multiple primary cancers, responses of ICB therapy in bone metastases remain extremely poor, largely due to the highly immunosuppressive bone metastasis microenvironment. However, the current understanding of bone metastasis microenvironment is still incomplete, and specific treatment targets for patients with bone metastasis are still lacking. Methods: Transcriptome sequencing data of gastric and breast cancer bone metastasis samples from The TCGA and GEO databases were obtained. The correlation between DKK1 expression and prognosis, intertumoral immune infiltration of bone-metastatic patients was analyzed. Mouse bone metastasis models from gastric, breast and lung cancer were established, and in vivo treatment efficacy of DKK1 and/or zoledronic acid was evaluated by micro-computed tomography (CT), micro-magnetic resonance imaging (MRI) and immunohistochemistry (IHC) staining. The changes of immune components wthin bone-tumor microenvironment were explored via flow cytometry, CyTOF and scRNA-seq analysis. The impact of DKK1 on different immune cell types was analyzed via in vitro co-culture models. Results: Serum detection of gastric cancer patients from our center showed that compared with non-metastatic patients, DKK1 concentration in patients with bone metastasis was the significantly increased (p&amp;lt;0.0001); and compared with other metastatic sites of breast cancer patients, bone metastases had the highest level of DKK1 mRNA expression (p&amp;lt;0.05). Using multiple bone metastasis mouse models, we found that DKK1 blockade significantly controlled the tumor burden of bone metastases. Results of micro-CT and TRAP staining showed that the bone destruction and osteoclast activity within bone lesions were significantly inhibited after DKK1 blockade. In addition, results of flow cytometry and immunofluorescence staining on bone metastasis samples showed that both innate and adaptive anti-immune responses were obviously improved after DKK1 blockade, including increased infiltration of CD8+ T cells, M1 macrophages and decreased infiltration of M2 macrophages. Mechanistically, DKK1 directly induced inhibition of CD8+ T cell activation, M2 polarization of macrophages and maturation of osteoclasts, which all contributes to the immune suppression in the bone metastasis microenvironment. Finally, combined therapy of DKK1 blockade and zoledronic acid had synergistic treatment effects in bone metastases. Conclusion: Our study provides novel insights into the multiple role of DKK1 in the bone metastasis immune microenvironment. DKK1 is a potential immunotherapeutic target for bone metastases, and dual blockade of DKK1 and zoledronic acid is a promising combination immunotherapy strategy for patients with bone metastasis. Citation Format: Tao Shi, Kaijie Liang, Yipeng Zhang, Xiaoyu Zhou, Baorui Liu, Jia Wei. DKK1 blockade inhibits progression of bone metastases via multiple mechanisms and synergize with zoledronate treatment [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 5285.

Abstract 6490: Pt1a and sorafenib combination treatment exerts synergistic anti-hepatocellular carcinoma effect through RNA m6A methylation modification

Abstract Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a poor prognosis. The survival benefits of sorafenib in patients with advanced HCC are modest owing to acquired resistance. Accumulating evidence has demonstrated that cancer stemness is an important cause of drug resistance and the root cause of tumor recurrence. [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a) is a newly developed platinum-based drug containing N-heterocyclic carbene with proven anticancer properties against a range of tumor types. However, its role in targeting cancer stemness and its ability to sensitize cancer cells to overcome molecular-targeted therapy drug resistance in HCC remains elusive. Herein, we demonstrate the synergistic inhibitory effect of sorafenib and Pt1a combination treatment on HCC through RNA m6A methylation modification. In cultured HCC cells and patient-derived organoids, the drug combination synergistically reduced the cell viability and promoted cell apoptosis compared to single-drug treatment. Combination treatment also attenuated self-renewal, as evidenced by a marked decrease in tumor-initiating cancer cell frequency, as measured by limiting dilution spheroid formation assay. These findings were further validated in HCC patient-derived xenograft mouse models and a mouse HCC model induced by hydrodynamic tail vein delivery of NRAS+AKT coactivation plasmids. Notably, the combination treatment with sorafenib and Pt1a, but not a single treatment, led to a significant reduction in tumor burden. The combination treatment was also effective in decreasing tumor-initiating cell frequency, as measured by subjecting the harvested tumor cells for limiting dilution spheroid formation assay ex vivo. Mechanistically, integrative RNA-sequencing and thermal proteome profiling analyses both indicated the enrichment of m6A-related pathways in combination drug treatment. An increased global m6A level upon combination treatment was validated using m6A dot blotting, confirming that the synergistic effect may be mediated by the elevated global m6A level in HCC cells. Collectively, our study demonstrated that Pt1a and sorafenib combination treatment synergistically inhibited the viability and stemness of HCC cells by increasing global RNA m6A level. These findings supported the potential of Pt1a as a therapeutic option for HCC and overcoming sorafenib drug resistance. Ongoing studies are focused on identifying m6A regulators and downstream targets involved in combination treatment. Citation Format: Yinjia Huang, Yalu Cui, Ianto Bosheng Huang, Yanyan Wang, Yang Xuan, Pui Ki Wan, Chun Nam Lok, Chi Ming Che, Stephanie Ma. Pt1a and sorafenib combination treatment exerts synergistic anti-hepatocellular carcinoma effect through RNA m6A methylation modification [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 6490.

Abstract 4748: Aronia berry overcomes gemcitabine resistance by regulating the MYD88/NF-kB/P-glycoprotein pathway in pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is lethal, which is partly due to the limited efficacy of Gemcitabine (Gem)-based chemotherapy, resulting from the development of acquired resistance to this regimen. Aronia berry extract (ABE) is a natural source of phenolic compounds known for its anti-cancer properties. Previous research has highlighted the ability of ABE to help overcome chemoresistance to conventional chemotherapies in various cancers. In this study, we interrogated the ability of ABE to overcome Gem-resistance (Gem-R) in PDAC and identify specific pathway(s) responsible for this anti-cancer efficacy. Methods: We performed a series of in-vitro experiments in Gem-R cells to evaluate the synergistic effect of combined treatment with Gem and ABE. Furthermore, we conducted a genomewide transcriptomic analysis to identify the critical regulatory pathways associated with chemoresistance and potential therapeutic targets of ABE in Gem-R PDAC cells. The cell culture findings were validated in patient-derived 3D organoids. Results: The combined treatment with ABE and Gem in Gem-R cells exhibited significant synergistic anticancer effects on cell viability, proliferation, migration, and invasion. The transcriptomic analysis revealed that the NF-κB signaling pathway was associated with Gem-R (p&amp;lt;0.05), with a significant upregulation of MYD88. Additionally, MYD88 was significantly associated with overall survival in PDAC patients in the TCGA cohort (HR=1.58, P=0.045). The MYD88/NF-κB signaling is associated with chemoresistance as it can upregulate the efflux transporters like P-glycoprotein (P-gp). Our results confirmed that combined treatment inhibited the NF-κB signaling pathway by suppressing MYD88 and downregulating P-gp expression to overcome Gem-R. Finally, the combined treatment demonstrated superior anti-cancer activity in 3D organoids by reducing both their number and size (P&amp;lt;0.05). Conclusion: We provide novel insights into the potential of ABE in overcoming Gem-R in PDAC cells by targeting the MYD88/NF-κb/P-gp axis, which offers a safe and inexpensive approach for improving therapeutic outcomes in this fatal malignancy. Citation Format: Yuan Li, Caiming Xu, Haiyong Han, Ajay Goel. Aronia berry overcomes gemcitabine resistance by regulating the MYD88/NF-kB/P-glycoprotein pathway in pancreatic ductal adenocarcinoma [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 4748.

Metasurface-enhanced multifunctional flag nanogenerator for efficient wind energy harvesting and environmental sensing

Wind energy, as a widely distributed and renewable energy resource, plays a crucial role in promoting self-powered wireless sensor networks and wind speed sensing. However, current research predominantly focuses on specific application purposes, lacking comprehensive investigations into integrated solutions. In this paper, a metasurface-enhanced multifunctional flag-type triboelectric nanogenerator (FTENG) is introduced, which enables efficient wind energy harvesting as well as accurate wind speed sensing over a wide range of wind speeds via the synergistic effect of metasurface treatment on the flagpole and flexible flag fixation approach. The flexible fixation maximally utilizes the upstream wake of metasurface configurations, boosting the energy harvesting power density by up to 23 times. The metasurface-enhanced FTENG with careful optimization, striking a balance between energy harvesting and sensing capabilities, achieves a linearity of 0.992 over a wind speed range of 2.3–14.4 m/s and a peak power density of 250 mW/m2. Finally, the FTENG demonstrates its excellent abilities to light LEDs, power the wireless sensor node (WSN), and serve as a self-powered environmental sensor. This work opens up an impactful possibility for developing versatile self-powered electronics by employing metasurface-enhanced wind energy harvesting techniques.

Therapeutic Effects of IL-1RA, M2 Cells, and Their Synergistic Impact on a Mouse Model of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a type of autoimmune disease that results in chronic inflammation of the joint synovial tissue, leading to joint damage and significant disability. Despite ongoing research, the exact cause of RA remains unclear, and current treatments have limitations. This study explores the potential of utilizing interleukin-1 receptor antagonist (IL-1RA) and anti-inflammatory macrophages polarized in the vicinity of the supernatant from allogeneic mesenchymal stem cells (MSCs) as a novel therapeutic approach for RA. An expression cassette containing the IL-1RA gene was constructed and expressed in E. coli BL21. The resulting protein was purified and stabilized for use in in vivo experiments. Bone marrow MSCs were isolated and used to produce anti-inflammatory M2 macrophages from the isolated peripheral blood monocytes. The macrophages were then used to treat mice with RA induced by collagen type II. The combination of IL-1RA and M2 macrophages improved clinical and histopathological symptoms of the disease, reduced levels of inflammatory factors, and modulated the immune system in the treated mouse groups. The results showed that this combinatory therapy had a synergistic effect for RA treatment. The simultaneous use of IL-1RA and M2 cells could be a promising approach for the treatment of RA. This combinatory therapy has the potential to improve the disease and decrease the severity of inflammation in patients with RA.

Immunotherapy and Radiation Therapy Combinatorial Approaches in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a prevalent and often fatal liver cancer, presents significant treatment challenges, especially in its advanced stages. This article delves into the promising approach of combining immunotherapy, particularly immune checkpoint inhibitors, with radiation therapy, a cornerstone of HCC management. Our review synthesizes current preclinical and clinical research, highlighting the potential synergistic effects of this combinational treatment. Emerging evidence suggests that this synergy enhances tumor control and improves patient survival rates. The combination leverages the localized, tumor-targeting ability of radiation therapy and the systemic, immune-boosting effects of immunotherapy, potentially overcoming the limitations inherent in each treatment modality when used separately. This integrative approach is especially promising in addressing the complex tumor microenvironment of HCC. However, the treatment landscape is nuanced, with challenges such as patient-specific response variability and potential resistance to therapies. Future research directions should focus on refining these combination strategies, tailoring them to individual patient profiles, and understanding the underlying mechanisms that govern the interaction between immunotherapy and radiation therapy. Such advancements could significantly improve HCC management, setting new standards for patient care and treatment efficacy.

Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy.

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria-based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine-mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria-mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria-synergized multimodal cancer therapies are highlighted.

Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics.

Bacteria-based therapy has spotlighted an unprecedented potential in treating a range of diseases, given that bacteria can be used as both drug vehicles and therapeutic agents. However, the use of bacteria for disease treatment often suffers from unsatisfactory outcomes, due largely to their suboptimal bioavailability, dose-dependent toxicity, and low targeting colonization. In the past few years, substantial efforts have been devoted to tackling these difficulties, among which methods capable of integrating bacteria with multiple functions have been extensively pursued. Different from conventional genetic engineering and modern synthetic bioengineering, surface modification of bacteria has emerged as a simple yet flexible strategy to introduce different functional motifs. Polydopamine, which can be easily formed via in situ dopamine oxidation and self-polymerization, is an appealing biomimetic polymer that has been widely applied for interfacial modification and functionalization. By virtue of its catechol groups, polydopamine can be efficiently codeposited with a multitude of functional elements on diverse surfaces.In this Account, we summarize the recent advances from our group with a focus on the interfacial polymerization-mediated functionalization of bacteria for advanced microbial therapy. First, we present the optimized strategy for bacterial surface modification under cytocompatible conditions by in situ dopamine polymerization. Taking advantage of the hydrogen bonding, π-π stacking, Michael addition, and Schiff base reaction with polydopamine, diverse functional small molecules and macromolecules are facilely codeposited onto the bacterial surface. Namely, monomodal, dual-modal, and multimodal surface modification of bacteria can be achieved by dopamine self-deposition, codeposition with a unitary composition, and codeposition with a set of multiple components, respectively. Second, we outline the regulation of bacterial functions by surface modification. The formed polydopamine surface endows bacteria with the ability to resist in vivo insults, such as gastrointestinal tract stressors and immune clearance, resulting in greatly improved bioavailability. Integration with specific ligands or therapeutic components enables the modified bacteria to increase targeting accumulation and colonization at lesion sites or play synergistic effects in disease treatment. Bacteria codeposited with different bioactive moieties, such as protein antigens, antibodies, and immunoadjuvants, are even able to actively interact with the host, particularly to elicit immune responses by either suppressing immune overactivation to promote the reversion of pathological inflammations or provoking protective innate and/or adaptive immunity to inhibit pathogenic invaders. Third, we highlight the applications of surface-modified bacteria as multifunctional living therapeutics in disease treatment, especially alleviating inflammatory bowel diseases via oral delivery and intervening in different types of cancer through systemic or intratumoral injection. Finally, we discuss the challenges and prospects of dopamine polymerization-mediated multifunctionalization for preparing advanced bacterial therapeutics as well as their bench to bedside translation. We anticipate that this Account can provide an insightful overview of bacterial therapy and inspire innovative thinking and new efforts to develop next-generation living therapeutics for treating various diseases.

Investigating the synergistic effects of immunotherapy and normalization treatment in modulating tumor microenvironment and enhancing treatment efficacy

We developed a comprehensive mathematical model of cancer immunotherapy that takes into account: i) Immune checkpoint blockers (ICBs) and the interactions between cancer cells and the immune system, ii) characteristics of the tumor microenvironment, such as the tumor hydraulic conductivity, interstitial fluid pressure, and vascular permeability, iii) spatial and temporal variations of the modeled components within the tumor and the surrounding host tissue, iv) the transport of modeled components through the vasculature and between the tumor-host tissue with convection and diffusion, and v) modeling of the tumor draining lymph nodes were the antigen presentation and the development of cytotoxic immune cells take place. Our model successfully reproduced experimental data from various murine tumor types and predicted immune system profiling, which is challenging to achieve experimentally. It showed that combination of ICB therapy and normalization treatments, that aim to improve tumor perfusion, decreases interstitial fluid pressure and increases the concentration of both innate and adaptive immune cells at the tumor center rather than the periphery. Furthermore, using the model, we investigated the impact of modeled components on treatment outcomes. The analysis found that the number of functional vessels inside the tumor region and the ICB dose administered have the largest impact on treatment outcomes.

Evolution and regulation of microstructure and properties of CuCr alloys prepared by self-propagating metallurgy

In this paper, the evolution of microstructure and properties of CuCr50 alloy prepared by self-propagating method is analyzed through the synergistic effect of forging and heat treatment. It is found that when the forging ratio is 1.15, the Cr-rich phase in the forged CuCr50 alloy undergoes plastic deformation to a certain extent, the average particle size of the Cr-rich phase is refined from 22.3 μm to 20.5 μm, and the solid solution Cu content in the Cr-rich phase increases. After heat treatment (solid solution + aging treatment) of forged CuCr50 alloy, it is found that the average particle size of Cr-rich phase is further refined to 18.9 μm, and the results of EBSD show that the grains in the bulk Cr-rich phase decrease from 1.85 μm to 0.76 μm, and the lattice orientation of Cr-rich and Cu-rich grains shift to <111> plane. At this time, the second dispersed phase exists in the Cu-rich matrix, and the solid solution of Cu in the Cr-rich phase exists in spherical form. After SHS + forging + heat treatment, the density of CuCr50 alloy increased from 7.51 g cm−3 to 7.98 g cm−3, and the electrical conductivity increased from 12.5 MS m−1 to 18.7 MS m−1. Compared with SHS + heat treatment, the electrical conductivity of CuCr alloy increased by 13.3%. The performance test of 12 kV simulated vacuum interrupter shows that the insulation and breaking properties of the prepared CuCr50 alloy contact material are obviously better than those reported in literature and the requirements of national standard, which provides a theoretical basis for the preparation of high performance CuCr alloy.

Operando investigation of the synergistic effect of electric field treatment and copper for bacteria inactivation

As the overuse of chemicals in our disinfection processes becomes an ever-growing concern, alternative approaches to reduce and replace the usage of chemicals is warranted. Electric field treatment has shown promising potential to have synergistic effects with standard chemical-based methods as they both target the cell membrane specifically. In this study, we use a lab-on-a-chip device to understand, observe, and quantify the synergistic effect between electric field treatment and copper inactivation. Observations in situ, and at a single cell level, ensure us that the combined approach has an enhancement effect leading more bacteria to be weakened by electric field treatment and susceptible to inactivation by copper ion permeation. The synergistic effects of electric field treatment and copper can be visually concluded here, enabling the further study of this technology to optimally develop, mature, and scale for its various applications in the future.

Synergistic effects of graphene additives and piston ring surface treatment on friction properties of engine oil

The use of nano-additives improves the performance of lubricants by minimizing energy loss due to friction and wear. In this study, tribological properties of cylinder liner-piston ring were improved by modifying monolayer graphene with surfactants. Additionally, surface chemical chromium coating and chemical heat treatment were conducted on the friction surfaces of specially made piston ring samples to further enhance the friction of piston ring. From the comparison of experimental results, the best lubrication performance was exhibited by the use of 0.05 wt% modified graphene nano-lubricant, which reduced the friction coefficient by approximately 31.1% and improved the anti-wear performance by approximately 59.6% compared to the base oil. In addition, the effect of the graphene nano-lubricant on the friction performance of chromium-coated samples was more substantial than that of the chemically heat-treated samples. Under high-temperature and heavy-load conditions, the corresponding friction coefficient was reduced by 15.5% and 34%, respectively, when compared to the base oils. This can be attributed to the porous surface of the chromium-coated sample, which promotes the storage of the graphene nano-lubricant. The results highlight the synergistic effect of graphene additives and piston ring surface treatment on the tribological performance.

Modeling cancer cells and tumor vasculature dynamics by serum biomarkers in HCC patients with different response to TKIs, TACE and TARE suggests a synergistic effect of systemic and endovascular treatments

Modeling cancer cells and tumor vasculature dynamics by serum biomarkers in HCC patients with different response to TKIs, TACE and TARE suggests a synergistic effect of systemic and endovascular treatments

Synergistic effect of surface treatment and adhesive type on bonding performance of thin Al6061 joints for automotive applications

The effects of different surface treatments (grinding, plasma surface treatment, and grinding followed by the plasma (GrPl) process) and various adhesives (cyanoacrylate, Bisphenol A (BPA)-based, and Bisphenol A and Bisphenol F (BPA/F)-based adhesive) on the bonding performance of single-lap joints manufactured from thin Al6061-T4 aluminium alloy sheets were investigated in this study. Contact angle measurement was carried out to evaluate the influence of surface treatments on the wettability of the surface of the aluminium alloy adherends. The contact angle on the surface of the untreated sheet was measured to be 71.8°. However, after applying the GrPl process on the ground surface, the contact angle could be reduced to 47° and 25.9° in the parallel and perpendicular directions to the grinding direction, respectively. Shear testing was performed to evaluate the mechanical behaviour of the single-lap joints of aluminium alloy sheets. The shear strengths of BPA/F-based, cyanoacrylate, and BPA-based adhesive-bonded joints produced from ground adherends improved by 47 %, 54 %, and 72 %, respectively. The synergistic impact of GrPl treatment resulted in 126 %, 123 %, and 174 % enhancement in shear strength of BPA/F-based, cyanoacrylate, and BPA-based adhesive-bonded joints, respectively. When the temperature was raised from room temperature to 60 °C, the bonding performances of all single-lap joints deteriorated due to the decrease in the strength of the adhesive. However, the joints treated with plasma had the highest shear strength at 60 °C. While the BPA-based adhesive had the most beneficial impact on improving the shear strength of single-lap joints at room temperature, the opposite result was obtained at 60 °C. All the findings have indicated that the influence of adhesive on the bonding performance of aluminium alloy joints varied significantly depending on the surface treatment and temperature.

Synergistic effects of ultrasonic vibration and isothermal treatment on the peritectic transformation and microstructure evolution of Cu–Sn alloy

To facilitate and even complete the peritectic transformation, the ultrasonic vibration (USV) and isothermal treatment were applied to the solidification process of Cu–70Sn alloy. It was found that the peritectic transformation was difficult to carry out due to the limited atomic diffusion under the normal solidification condition. With the single isothermal treatment, the peritectic transformation could be enhanced to some extent, with a small amount of η phase (Cu6Sn5) formed relying on the coarse elongated primary ε phase (Cu3Sn), but the further prolongation of isothermal time led to the abnormally coarsening of microstructure. When the molten alloy was subjected to 1500W USV and 30 min isothermal treatment, the peritectic transformation was dramatically facilitated. The ultrasonic-induced effects of cavitation and acoustic streaming play an important role in the remarkable reduction in the curvature radius of primary ε phase, thereby enhancing the diffusion of Sn solute atoms from the liquid phase to the interior of ε phase at the following isothermal stage. Accordingly, the transformation degree of ε phase to η phase was increased up to 77 %, and there was a high volume fraction of primary ε phase could thoroughly complete the peritectic transformation.

Arresting the G2/M phase empowers synergy in magnetic nanomanipulator-based cancer mechanotherapy and chemotherapy

Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.

SIRT1 overexpression by melatonin and resveratrol combined treatment attenuates premature ovarian failure through activation of SIRT1/FOXO3a/BCL2 pathway

AimTo evaluate the synergistic effect of combined treatment with melatonin (MEL) and resveratrol (RES) in cisplatin (CIS)-induced premature ovarian failure (POF) model in rats and to elucidate the molecular mechanism of this therapeutic effect. Material & methodsFemale Sprague Dawley rats were divided into 7 experimental groups as follows; CONT (Control), CIS, MEL, RES, POF + MEL, POF + RES, and POF + MEL + RES. H&E staining was performed to evaluate follicular cell vacuolization/degeneration, vascular congestion/hemorrhage, and inflammation, by using an ordinal scale from 0 to 4 to grade the severity of observed changes (0 = normal, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). Zona pellucida integrity and connective tissue amount in the ovarian tissue were detected using PAS & Masson Trichrome staining. The immunofluorescence method was used to determine the immune localizations of pH2Ax, SIRT1, FOXO3a, and BCL2. The connective tissue amounts and immunoreactivity staining intensities were measured using ImageJ. The gene expression of SIRT1, FOXO3a, and BCL2 was determined using RT-PCR. Serum estrogen hormone levels were measured by ELISA. Statistically, Bonferroni correction was performed, and p < 0.002 were considered significant. ResultsA significant difference was observed in the POF group compared to the CONT group in all parameters except tertiary follicle count and hemorrhage. The decrease in the number of atretic follicles in the POF + MEL + RES group was found significant compared to both POF + MEL and POF + RES groups. The expression of pH2Ax, SIRT1, FOXO3a, and BCL2 at the protein level and SIRT1 and BCL2 at the mRNA level were significant in the POF + MEL + RES group compared to the POF group. Between the single and combination treatment groups, the difference in protein level was found in pH2Ax, SIRT1, FOXO3a, and BCL2 expression. The POF + MEL + RES group exhibited significantly higher SIRT1 mRNA expression compared to the groups receiving single treatments. ConclusionThe present study provides evidence that MEL and RES have synergistic effects in preventing the decrease in follicle reserve and increase in DNA break (pH2Ax) and follicle atresia in POF ovaries. This therapeutic effect is mediated by SIRT1 overexpression and activation of the SIRT1/FOXO3a/BCL2 pathway.