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Value in mergers and acquisitions (M&A) derives from the synergistic combination of an acquirer and a target. We advance the existing conceptualization of synergies in three ways. First, we develop...

Solving the problem of antibiotic resistance requires the development of new antimicrobial drugs and/or new therapeutic strategies. A promising strategy to combat resistant pathogens is to combine antimicrobials with different mechanisms of action, since it is more difficult for bacteria to develop resistance against several mechanisms at the same time. Of particular interest are antimicrobial peptides, resistance to which develops much more slowly than to conventional antibiotics. Most of the superbugs that pose a serious threat to human health today are gram-negative. Their outer membrane plays the role of a barrier for antimicrobial agents whose targets are located in the inner membrane or in the cytoplasm of bacteria. Review of research reports over the past seven years suggests that combining polymyxins with nisin results in a synergistic or additive antimicrobial effect. Polymyxin- nisin combinations have been shown to be effective against clinically significant gram-negative pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli. The probable mechanism of synergy consists in providing polymyxin due to the violation of the integrity of the outer membrane of nisin access to the target on the inner membrane (lipid II) with the subsequent realization of its antimicrobial potential. The synergistic interaction of an antibiotic with a lantibiotic allows to reduce the concentration of the antibiotic, thereby reducing the likelihood of developing toxic effects. The additive effect also has an important positive value, as it is accompanied by a decrease of antibiotic`s minimal inhibition concentration and indicates the possibility of restoring the sensitivity of bacteria to it. Therefore, synergistic polymyxin-nisin combinations deserve further study and application in clinical practice., {"references":["1. \tBreijyeh, Z.; Jubeh, B.; Karaman, R. Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It. Molecules 2020, 25 (6), 1340. https://doi.org/10.3390/molecules25061340.","2. \tChurch, N. A.; McKillip, J. L. Antibiotic Resistance Crisis: Challenges and Imperatives. Biologia (Bratisl.) 2021, 76 (5), 1535–1550. https://doi.org/10.1007/s11756-021-00697-x.","3. \tTacconelli, E.; Carrara, E.; Savoldi, A.; et al. Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis. Lancet Infect. Dis. 2018, 18 (3), 318–327. https://doi.org/10.1016/S1473-3099(17)30753-3.","4. \tWHO. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics (WHO, 2017).","5. \tChahine, E. B.; Dougherty, J. A.; Thornby, K.-A.; et al. Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance? Ann. Pharmacother. 2022, 56 (4), 441–462. https://doi.org/10.1177/10600280211031390.","6. \tLewies, A.; Plessis, L. H. D.; Wentzel, J. F. The Cytotoxic, Antimicrobial and Anticancer Properties of the Antimicrobial Peptide Nisin Z Alone and in Combination with Conventional Treatments. In Cytotoxicity; Çelik, T. A., Ed.; InTech, 2018. https://doi.org/10.5772/intechopen.71927.","7. \tSoltani, S.; Hammami, R.; Cotter, P. D.; et al. Bacteriocins as a New Generation of Antimicrobials: Toxicity Aspects and Regulations. FEMS Microbiol. Rev. 2021, 45 (1), fuaa039. https://doi.org/10.1093/femsre/fuaa039.","8. \tJahangiri, A.; Neshani, A.; Mirhosseini, S. A.; et al. Synergistic Effect of Two Antimicrobial Peptides, Nisin and P10 with Conventional Antibiotics against Extensively Drug-Resistant Acinetobacter Baumannii and Colistin-Resistant Pseudomonas Aeruginosa Isolates. Microb. 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Colistin Resistance in Enterobacterales Strains – A Current View. Pol. J. Microbiol. 2019, 68 (4), 417–427. https://doi.org/10.33073/pjm-2019-055.","21. \tNation, R.; Rigatto, M.; Falci, D.; et al. Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity. Antibiotics 2019, 8 (1), 24. https://doi.org/10.3390/antibiotics8010024.","22. \tNang, S. C.; Li, J.; Velkov, T. The Rise and Spread of Mcr Plasmid-Mediated Polymyxin Resistance. Crit. Rev. Microbiol. 2019, 45 (2), 131–161. https://doi.org/10.1080/1040841X.2018.1492902.","23. \tBertani, B.; Ruiz, N. Function and Biogenesis of Lipopolysaccharides. EcoSal Plus 2018, 8 (1), ecosalplus.ESP-0001-2018. https://doi.org/10.1128/ecosalplus.ESP-0001-2018.","24. \tSun, J.; Rutherford, S. T.; Silhavy, T. J.; et al. Physical Properties of the Bacterial Outer Membrane. Nat. Rev. Microbiol. 2022, 20 (4), 236–248. https://doi.org/10.1038/s41579-021-00638-0.","25. \tLi, Z.; Velkov, T. Polymyxins: Mode of Action. In Polymyxin Antibiotics: From Laboratory Bench to Bedside; Li, J., Nation, R. L., Kaye, K. S., Eds.; Springer International Publishing: Cham, 2019; Vol. 1145, pp 37–54. https://doi.org/10.1007/978-3-030-16373-0_4.","26. \tKhadka, N. K.; Aryal, C. M.; Pan, J. Lipopolysaccharide-Dependent Membrane Permeation and Lipid Clustering Caused by Cyclic Lipopeptide Colistin. ACS Omega 2018, 3 (12), 17828–17834. https://doi.org/10.1021/acsomega.8b02260.","27. \tSi, W.; Wang, L.; Usongo, V.; et al. Colistin Induces S. Aureus Susceptibility to Bacitracin. Front. Microbiol. 2018, 9, 2805. https://doi.org/10.3389/fmicb.2018.02805.","28. \tLima, M. R.; Ferreira, G. F.; Nunes Neto, W. R.; et al. Evaluation of the Interaction between Polymyxin B and Pseudomonas Aeruginosa Biofilm and Planktonic Cells: Reactive Oxygen Species Induction and Zeta Potential. BMC Microbiol. 2019, 19 (1), 115. https://doi.org/10.1186/s12866-019-1485-8.","29. \tYu, Z.; Zhu, Y.; Fu, J.; et al. Enhanced NADH Metabolism Involves Colistin-Induced Killing of Bacillus Subtilis and Paenibacillus Polymyxa. Molecules 2019, 24 (3), 387. https://doi.org/10.3390/molecules24030387.","30. \tKoen, N.; van Breda, S. V.; Loots, D. T. Elucidating the Antimicrobial Mechanisms of Colistin Sulfate on Mycobacterium Tuberculosis Using Metabolomics. Tuberculosis 2018, 111, 14–19. https://doi.org/10.1016/j.tube.2018.05.001.","31. \tThe European Committee on Antimicrobial Susceptibility Testing.","32. \tClinical Laboratory and Standards Instiute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing, 30th e.","33. \tGai, Z.; Samodelov, S.; Kullak-Ublick, G.; et al. Molecular Mechanisms of Colistin-Induced Nephrotoxicity. Molecules 2019, 24 (3), 653. https://doi.org/10.3390/molecules24030653.","34. \tVaara, M. New Polymyxin Derivatives That Display Improved Efficacy in Animal Infection Models as Compared to Polymyxin B and Colistin. Med. Res. Rev. 2018, 38 (5), 1661–1673. https://doi.org/10.1002/med.21494.","35. \tGallardo-Godoy, A.; Hansford, K.; Muldoon, C.; et al. Structure-Function Studies of Polymyxin B Lipononapeptides. Molecules 2019, 24 (3), 553. https://doi.org/10.3390/molecules24030553.","36. \tBrennan-Krohn, T.; Pironti, A.; Kirby, J. E. Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae. Antimicrob. Agents Chemother. 2018, 62 (10), e00873-18. https://doi.org/10.1128/AAC.00873-18.","37. \tMacNair, C. R.; Stokes, J. M.; Carfrae, L. A.; et al. Overcoming Mcr-1 Mediated Colistin Resistance with Colistin in Combination with Other Antibiotics. Nat. Commun. 2018, 9 (1), 458. https://doi.org/10.1038/s41467-018-02875-z.","38. \tLoose, M.; Naber, K. G.; Hu, Y.; et al. Urinary Bactericidal Activity of Colistin and Azidothymidine Combinations against Mcr-1-Positive Colistin-Resistant Escherichia Coli. Int. J. Antimicrob. Agents 2019, 54 (1), 55–61. https://doi.org/10.1016/j.ijantimicag.2019.04.011.","39. \tTyrrell, J. M.; Aboklaish, A. F.; Walsh, T. R.; et al. The Polymyxin Derivative NAB739 Is Synergistic with Several Antibiotics against Polymyxin-Resistant Strains of Escherichia Coli, Klebsiella Pneumoniae and Acinetobacter Baumannii. Peptides 2019, 112, 149–153. https://doi.org/10.1016/j.peptides.2018.12.006.","40. \tThomas, V. M.; Brown, R. M.; Ashcraft, D. S.; et al. Synergistic Effect between Nisin and Polymyxin B against Pandrug-Resistant and Extensively Drug-Resistant Acinetobacter Baumannii. Int. J. Antimicrob. Agents 2019, 53 (5), 663–668. https://doi.org/10.1016/j.ijantimicag.2019.03.009.","41. \tLewies, A.; Wentzel, J. F.; Jordaan, A.; et al. Interactions of the Antimicrobial Peptide Nisin Z with Conventional Antibiotics and the Use of Nanostructured Lipid Carriers to Enhance Antimicrobial Activity. Int. J. Pharm. 2017, 526 (1–2), 244–253. https://doi.org/10.1016/j.ijpharm.2017.04.071.","42. \tO'Sullivan, J. N.; O'Connor, P. M.; Rea, M. C.; et al. Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus Capitis Sourced from the Human Skin Microbiota. J. Bacteriol. 2020, 202 (3). https://doi.org/10.1128/JB.00639-19.","43. \tHatziioanou, D.; Gherghisan-Filip, C.; Saalbach, G.; et al. Discovery of a Novel Lantibiotic Nisin O from Blautia Obeum A2-162, Isolated from the Human Gastrointestinal Tract. Microbiology 2017, 163 (9), 1292–1305. https://doi.org/10.1099/mic.0.000515.","44. \tLawrence, G. W.; Garcia-Gutierrez, E.; Walsh, C. J.; et al. Nisin G Is a Novel Nisin Variant Produced by a Gut-Derived Streptococcus Salivarius; preprint; Microbiology, 2022. https://doi.org/10.1101/2022.02.15.480493.","45. \tMeade; Slattery; Garvey. Bacteriocins, Potent Antimicrobial Peptides and the Fight against Multi Drug Resistant Species: Resistance Is Futile? Antibiotics 2020, 9 (1), 32. https://doi.org/10.3390/antibiotics9010032.","46. \tEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Younes, M.; Aggett, P.; et al. Safety of Nisin (E 234) as a Food Additive in the Light of New Toxicological Data and the Proposed Extension of Use. EFSA J. 2017, 15 (12). https://doi.org/10.2903/j.efsa.2017.5063.","47. \tBarbosa, A. A. T.; de Melo, M. R.; da Silva, C. M. R.; et al. Nisin Resistance in Gram-Positive Bacteria and Approaches to Circumvent Resistance for Successful Therapeutic Use. Crit. Rev. Microbiol. 2021, 47 (3), 376–385. https://doi.org/10.1080/1040841X.2021.1893264.","48. \tLi, Q.; Montalban-Lopez, M.; Kuipers, O. P. Increasing the Antimicrobial Activity of Nisin-Based Lantibiotics against Gram-Negative Pathogens. Appl. Environ. Microbiol. 2018, 84 (12), e00052-18. https://doi.org/10.1128/AEM.00052-18.","49. \tPrince, A.; Sandhu, P.; Ror, P.; et al. Lipid-II Independent Antimicrobial Mechanism of Nisin Depends On Its Crowding And Degree Of Oligomerization. Sci. Rep. 2016, 6 (1), 37908. https://doi.org/10.1038/srep37908.","50. \tGalván Márquez, I. J.; McKay, B.; Wong, A.; et al. Mode of Action of Nisin on Escherichia Coli. Can. J. Microbiol. 2020, 66 (2), 161–168. https://doi.org/10.1139/cjm-2019-0315.","51. \tJensen, C.; Li, H.; Vestergaard, M.; et al. Nisin Damages the Septal Membrane and Triggers DNA Condensation in Methicillin-Resistant Staphylococcus Aureus. Front. Microbiol. 2020, 11, 1007. https://doi.org/10.3389/fmicb.2020.01007.","52. \tÖzdemir, F. N.; Buzrul, S.; Özdemir, C.; et al. Determination of an Effective Agent Combination Using Nisin against Salmonella Biofilm. Arch. Microbiol. 2022, 204 (3), 167. https://doi.org/10.1007/s00203-022-02766-4.","53. \tChi, H.; Holo, H. Synergistic Antimicrobial Activity Between the Broad Spectrum Bacteriocin Garvicin KS and Nisin, Farnesol and Polymyxin B Against Gram-Positive and Gram-Negative Bacteria. Curr. Microbiol. 2018, 75 (3), 272–277. https://doi.org/10.1007/s00284-017-1375-y.","54. \tField, D.; Seisling, N.; Cotter, P. D.; et al. Synergistic Nisin-Polymyxin Combinations for the Control of Pseudomonas Biofilm Formation. Front. Microbiol. 2016, 7. https://doi.org/10.3389/fmicb.2016.01713.","55. \tMathur, H.; Field, D.; Rea, M. C.; et al. Fighting Biofilms with Lantibiotics and Other Groups of Bacteriocins. Npj Biofilms Microbiomes 2018, 4 (1), 9. https://doi.org/10.1038/s41522-018-0053-6"]}

The natural product family of the fusicoccanes (FCs) has been shown to display anti-cancer activity, especially when combined with established therapeutic agents. FCs stabilize 14-3-3 protein-protein interactions (PPIs). Here, we tested combinations of a small library of FCs with interferon α (IFNα) on different cancer cell lines and report a proteomics approach to identify the specific 14-3-3 PPIs that are induced by IFNα and stabilized by FCs in OVCAR-3 cells. Among the identified 14-3-3 target proteins are THEMIS2, receptor interacting protein kinase 2 (RIPK2), EIF2AK2, and several members of the LDB1 complex. Biophysical and structural biology studies confirm these 14-3-3 PPIs as physical targets of FC stabilization, and transcriptome as well as pathway analyses suggest possible explanations for the observed synergistic effect of IFNα/FC treatment on cancer cells. This study elucidates the polypharmacological effects of FCs in cancer cells and identifies potential targets from the vast interactome of 14-3-3s for therapeutic intervention in oncology.

The advancement and growth of nanotechnology lead to realizing new and novel multi-metallic nanostructures with well-defined sizes and morphology, resulting in an improvement in their performance in various catalytic applications. The trimetallic nanostructured materials are synthesized and designed in different architectures for energy conversion electrocatalysis. The as-synthesized trimetallic nanostructures have found unique physiochemical properties due to the synergistic combination of the three different metals in their structures. A vast array of approaches such as hydrothermal, solvothermal, seed-growth, galvanic replacement reaction, biological, and other methods are employed to synthesize the trimetallic nanostructures. Noteworthy, the trimetallic nanostructures showed better performance and durability in the electrocatalytic fuel cells. In the present review, we provide a comprehensive overview of the recent strategies employed for synthesizing trimetallic nanostructures and their energy-related applications. With a particular focus on hydrogen evolution, alcohol oxidations, oxygen evolution, and others, we highlight the latest achievements in the field.

Most studies of animal coloration focus on spectral colours, which are colours evoked by single peaks within the wavelengths of visible light. It is poorly understood how non-spectral colours (those produced by a combination of reflectance peaks) are produced, despite their potential significance to both animal communication and biomimicry. Moreover, although both pigmentary and structural colour production mechanisms have been well characterized in feathers independently, their interactions have received considerably less attention, despite their potential to broaden the available colour spectrum. Here, we investigate the colour production mechanisms of the purple feathers of the purple-breasted cotinga (Cotinga cotinga). The purple feather colour results from both the coherent scattering of light by a sphere-type nanomatrix of β-keratin and air (spongy layer) in the barbs, which produces a blue–green colour, and the selective absorption of light in the centre of the bird-visible spectrum by the methoxy-carotenoid, cotingin. This unusual combination of carotenoid and nanostructure with a central air vacuole, in the absence of melanin, is a blueprint of a synergistic way to produce a non-spectral colour that would be difficult to achieve with only a single colour production mechanism.

Gliomas and glioblastoma comprise the majority of brain malignancies and are difficult to treat despite standard of care and advances in immunotherapy. The challenges of controlling glioma growth and recurrence involve the uniquely immunosuppressive tumor microenvironment and systemic blunting of immune responses. In addition to highlighting key features of glioma and glioblastoma composition and immunogenicity, this review presents several future directions for immunotherapy, such as vaccines and synergistic combination treatment regimens, to better combat these tumors.

The chiral (salen)Cr(III)/BF3·OEt2 catalytic combination was found to be an effective catalyst for intramolecular Friedel–Crafts cyclization of electron-deficient Morita–Baylis–Hillman adducts. In presence of mild reaction conditions the chiral (salen)Cr(III)/BF3·OEt2 complex affords 2-substituted-1H-indenes from unique substrates of Morita–Baylis–Hillman adducts via an easy operating practical procedure.

In the past three years, the use of combinational chemodynamic therapy (CDT) and photodynamic therapy (PDT) for antitumor treatments has exploded. Combinational antitumor CDT/PDT (C/PDT) brings promises of enhanced efficacy by using synergistic mechanisms.

Introduction: TNF-α/NF-kB signaling pathway plays an important role in promoting the inflammatory process and growth of breast cancer. Accordingly, the aim of the present study was to investigate the synergistic combination effect of endurance exercise with curcumin on breast cancer progression through TNF-α/NF-kB signaling axes in female BALB/c mice with breast cancer. Methods: The design of the present study was experimental. After transplanting 4T1 breast cancer into the right flank of 40 BALB/c mice, all mice were randomly divided into four groups, including endurance training (E), endurance training-curcumin (EC), curcumin (CC), and control (C). Then, E and EC groups (5 days per week) were performed for 5 weeks. Curcumin (6 times per week) was given by gavage to EC and CC groups for five weeks. The intratumoral expression of TNF-α and NF-kβ were measured using the qRT-PCR method. One-way analysis of variance and LSD post hoc test with SPSS version 16 were used for statistical analysis. P< 0.05 was considered statistically significant. Results: A significant decline in cancer growth and the gene expression of NF-kβ and TNF-α was observed in E, CC, and EC compared to the C group (P =0.001). Furthermore, a significant decline in expression of both genes was observed in EC compared with E. Conclusion: Endurance training combined with curcumin supplementation has a more effective role in reducing TNF-α and NF-κβ, and slowing the growth of breast cancer cells when compared with either of other interventions alone.

The insertion of nanoparticles into smart hydrogels can diversify their functionalities by a synergistic combination of the components properties within the hydrogels. While these hybrid systems are attractive to the biomaterials field, careful design and control of their properties are required since the new interactions between the polymer and the nanoparticles can result in changes or the loss of hydrogels stimuli response. In order to understand the physicochemical aspects of the thermoresponsive systems, nanocomposites of poly(N-vinylcaprolactam) (PNVCL) and silica nanoparticles with different sizes and concentrations were synthesized. The UV-vis and DLS techniques showed that the PNVCL has a sharp phase transition at 34 °C, while the nanocomposites have a diffuse transition. The nanocomposites showed an initial coil-globule transition before the phase transition takes place. This was identified by the evolution of the hydrodynamic diameter of the nanocomposite globules before the cloud point temperature (Tcp), which remained constant for PNVCL. This new transition profile can be described by two stages in which microscopic volume transitions occur first, followed by the macroscopic transition that forms the hydrogel. These results show that the proposed nanocomposites can be designed to have tunable stimuli response to smaller temperature variations with the formation of intermediate globule states.

The anti-inflammatory properties of the combination of meloxicam and atypical NSAID N-acetyl-L-proline (Groceprol®) after intragastric administration in a model of carrageenan paw edema in mice were studied. The average effective dose of N-acetyl-L-proline calculated by the regression analysis method in this model was 414 mg/kg, and the average effective dose of meloxicam was 2.85 mg/kg. In the combination in a ratio of 40:1, the activity of the compounds increases significantly, the ED50 of meloxicam decreases to 1 mg/kg, a similar value of N-acetyl-L-proline becomes 43 mg/kg. The same trend was also observed with another mass ratio of components of 20:1. The analysis of the pharmacodynamics of the combination of drugs according to the T. Chou method showed an additive type of interaction, typical for compounds with different mechanisms of primary action. It was established that a combination of N-acetyl-L-proline and meloxicam in the weight ratios of 40:1 and 20:1 demonstrate synergism, allowing to reduce the dose of the components in 2.7–9.6 times as compared with the effect of the drugs individually.The results of the study are the experimental justification for the use of anti-inflammatory synergistic combination of N-acetyl-L-proline and meloxicam.

Combination drug therapies have become an integral part of precision oncology, and while evidence of clinical effectiveness continues to grow, the underlying mechanisms supporting synergy are poorly understood. Immortalized human lymphoblastoid cell lines (LCLs) have been proven as a particularly useful, scalable and low-cost model in pharmacogenetics research, and are suitable for elucidating the molecular mechanisms of synergistic combination therapies. In this review, we cover the advantages of LCLs in synergy pharmacogenomics and consider recent studies providing initial evidence of the utility of LCLs in synergy research. We also discuss several opportunities for LCL-based systems to address gaps in the research through the expansion of testing regimens, assessment of new drug classes and higher-order combinations, and utilization of integrated omics technologies.

The activation of molecular oxygen is a fundamental step in almost all catalytic oxidation reactions. We have studied this topic and the role of surface vacancies for Co3O4(100) films with a synergistic combination of experimental and theoretical methods. We show that the as‐prepared surface is B‐layer terminated and that mild reduction produces oxygen single and double vacancies in this layer. Oxygen adsorption experiments clearly reveal different superoxide species below room temperature. The superoxide desorbs below ca. 120 K from a vacancy‐free surface and is not active for CO oxidation while superoxide on a surface with oxygen vacancies is stable up to ca. 270 K and can oxidize CO already at the low temperature of 120 K. The vacancies are not refilled by oxygen from the superoxide, which makes them suitable for long‐term operation. Our joint experimental/theoretical effort highlights the relevance of surface vacancies in catalytic oxidation reactions., Activated molecular oxygen (superoxide, O2 −) can oxidize CO already at 120 K on B‐layer terminated Co3O4(100) with oxygen vacancies. This rendered scheme illustrates how a vibrational spectrum of the adsorbed superoxide is recorded with surface action spectroscopy.

Optoacoustic (OA, photoacoustic) imaging capitalizes on the synergistic combination of light excitation and ultrasound detection to empower biological and clinical investigations with rich optical contrast while effectively bridging the gap between micro and macroscopic imaging realms. State-of-the-art OA embodiments consistently provide images at micron-scale resolution through superficial tissue layers by means of focused illumination that can be smoothly exchanged for acoustic-resolution images at diffuse light depths of several millimetres to centimetres via ultrasound beamforming or tomographic reconstruction. Taken together, this unique multi-scale imaging capacity opens unprecedented capabilities for high-resolution in vivo interrogations of the skin at scalable depths. Moreover, diverse anatomical and functional information is retrieved via dynamic mapping of endogenous chromophores such as haemoglobin, melanin, lipids, collagen, water and others. This, along with the use of non-ionizing radiation, facilitates a clinical translation of the OA modalities. We review recent progress in OA imaging of the skin in preclinical and clinical studies exploiting the rich contrast provided by endogenous substances in tissues. The imaging capabilities of existing approaches are discussed in the context of initial translational studies on skin cancer, inflammatory skin diseases, wounds and other conditions.

Supramolecular drug self-delivery systems (SDSDSs) involving active drugs as building blocks linked by supramolecular interactions have been well defined as an advanced chemotherapy strategy. However, the lack of detecting release of drugs from SDSDSs at specific tumor sites inevitably leads to unsatisfactory therapeutic effects, owing to the lack of information regarding the administration of these drugs. In this work, predesigned platinum-containing supramolecular drug self-delivery nanomicelles (SDSDNMs) were employed to synchronously realize drug monitoring by computed tomography imaging, immediately reflecting the evolution of drug release and real-time treatment at the tumor site. The appropriate administration dosage (1.2 mg mL-1,100 μL) and the injection interval (once every 3 days) needed to guide the antitumor activity of SDSDNMs were then defined, thereby attaining the aim of efficient synergistic combination chemotherapy. In vivo tumor inhibition and histological analyses showed that SDSDNMs exhibited a strong tumor inhibition effect and good safety with respect to normal organs. Such a supramolecular drug self-delivery strategy with monitored functions may offer new potential opportunities for application in the field of synergistic combination chemotherapy.

The promotional effects of sodium on Fe5C2 catalysts for CO2 hydrogenation were systematically investigated by a synergistic combination of density functional theory (DFT) calculations and experime...

Background The bio-preservation of food products using various natural ingredients and metabolites from various types of beneficial microorganisms released during targeted fermentation is a method that simultaneously has a preservative effect on the food product and provides a model of its composition in order to ensure its functional and health properties. This double effect can be achieved by incorporating ingredients with proven preservative and functional effects into the food product, such as essential oils from various plant species and probiotic bacteria. The aim of the present research was to study the synergistic effect of selected probiotic lactic acid bacteria (LAB) and essential oils with high antimicrobial activity against pathogenic and spoilage microorganisms for the bio-preservation of chocolate mousse food emulsion. Methods The susceptibility of the selected probiotic strain Lactobacillus plantarum D2 to different concentrations of the selected lemon or grapefruit essential oil was examined using the disc-diffusion method. Nine chocolate mousse variants were prepared with the inclusion of free or immobilized cells of the probiotic strain L. plantarum D2 and/or lemon or grapefruit zest essential oils. The chocolate mousse variants were stored for 20 days in refrigerated conditions, and changes in the concentration of viable lactobacilli cells, the pH and the microbiological purity were monitored in accordance with standard requirements by taking samples on the 0th, 5th, 10th, 15th, and 20th days of storage. An organoleptic evaluation of the chocolate variants was performed on the 0th day. Results Concentrations of up to 1% lemon or grapefruit essential oil did not affect the growth of the probiotic strain L. plantarum D2, which revealed opportunities for their joint application for the bio-preservation of food emulsions. The obtained chocolate mousse variants were characterized by preserved organoleptic characteristics and microbiological safety. Free or immobilized probiotic L. plantarum D2 cells applied alone or in combination with lemon or grapefruit essential oils provided bio-preservation of the food emulsions, maintaining a high concentration of viable cells (106-107 cfu/g) during storage under refrigerated conditions for 20 days. Conclusions The combined application of free or immobilized probiotic LAB and lemon or grapefruit essential oils resulted in better bio-preservation results than in the use of probiotic LAB or essential oils alone, thus suggesting a synergistic effect between the two bio-preservative agents. Moreover, the obtained chocolate mousse emulsions can be classified as functional foods and the chocolate mousse food matrix can successfully be used as a vehicle for delivery of probiotic LAB to a wide range of food consumers. The obtained results and the developed successful bio-preservation strategy for the production of chocolate mousse food emulsions would provide grounds for the future selection of other probiotic lactobacilli strains, essential oils and synergistic combinations of them for the development of successful bio-preservation strategies for other types of food and beverage products.

Fueled by CRISPR-Cas technology, a synergistic combination of advances in genomics, synthetic biology and bioinformatics have ushered in an era of genome-guided natural product discovery and engineering. As a versatile, programmable DNA targeting tool, CRISPR-Cas is increasingly employed to accelerate host and pathway engineering of actinomycetes, which are prolific producers of bioactive natural products. Here, we discuss the current state of the art, challenges and opportunities of CRISPR-Cas strategies to discover, diversify and improve the production of natural products from actinomycetes. Special emphasis is placed on the rapidly expanding CRISPR-Cas toolboxes for genome editing of non-Streptomyces actinomycetes.

Microbially influenced corrosion (MIC) is responsible for significant damage to major marine infrastructure worldwide. While the microbes responsible for MIC typically exist in the environment in a synergistic combination of different species, the vast majority of laboratory-based MIC experiments are performed with single microbial pure cultures. In this work, marine grade steel was exposed to a single sulfate reducing bacterium (SRB, Desulfovibrio desulfuricans) and various combinations of bacteria (both pure cultures and mixed communities), and the steel corrosion studied. Differences in the microbial biofilm composition and succession, steel weight loss and pitting attack were observed for the various test configurations studied. The sulfate reduction phenotype was successfully shown in half-strength marine broth for both single and mixed communities. The highest corrosion according to steel weight loss and pitting, was recorded in the tests with D. desulfuricans alone when incubated in a nominally aerobic environment. The multispecies microbial consortia yielded lower general corrosion rates compared to D. desulfuricans or for the uninoculated control.

The understanding of drug-carrier interactions is essential for the design and applications of metal-organic framework (MOF)-based drug delivery systems. While such drug-carrier interactions can be fundamentally different for MOFs with or without defects. In this work, we revealed that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host-guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOF without defects, the loading capacity is greatly reduced. We employed solid-state nuclear magnetic resonance (NMR) and molecular simulations to elucidate the drug-carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects have been revealed.

Background Laser hair reduction is one of the most common laser procedures in dermatology. Laser systems available are Ruby at 694 nm, Alexandrite (755 nm), Diode (810nm), and Nd:YAG (1064 nm). Recently, devices presenting a combination of wavelengths have shown to produce high effective hair reduction with no related risks. This study was conducted with the Soprano Ice Platinum (Alma Lasers, GMBH, Germany) that emits a combination of three wavelengths at 755, 810, and 1064 nm in a single pulse. Aims To establish the efficacy and safety of novel triple wavelength laser hair reduction technology in skin types IV to V. Patients and methods This was an investigator initiated, single-center, prospective clinical study conducted between December 2017 and June 2019 with a total of 25 patients (23 female and two male) above 18 years with skin types IV and V, areas included are face, beard, neck, chest, and others. Results Hair reduction was assessed using the physician GAIS (global esthetic improvement scale) score: no results 0% reduction, poor 0%-25% reduction, average 25%-50%, good 50%-75%, and excellent 75%-100%. All 25 patients (mean age 28 years, range 18-52 y/o) completed all six sessions of the study. Conclusion Objective clinical assessment of hair reduction using the physician GAIS score in 90 anatomical sites scores an excellent reduction in 95.5% areas and good reduction in 80% areas. This current study shows that a synergistic combination of three diode laser wavelengths used for hair removal (755, 810, 1064 nm) is effective and safe to use in subjects skin types IV and V for facial and body hair.

Constructing the highly efficient and stable quasi-solid-state even solid-state devices is one of the most significant tendency in the field of quantum dots sensitized solar cells (QDSCs). Herein, highly efficient and stable quasi-solid-state (QS)-QDSCs devices were fabricated via synergistically combining the TiO2-sol interconnecting-modified photoanodes with alginate hydrogel (AH)-assisted electrolyte films. TiO2-sol binding agent could incorporate into the surface and voids of TiO2 particles, which increased the surface area and roughness for QDs loading and induced better connection between the neighboring particles. Meanwhile, the AH-assisted QS-electrolyte films possessed the crosslinking hydrogel network structure and exhibited the perfect interfacial contact with the modified TiO2 surface, thus enhancing the ion transport and redox reaction of polysulfide couple. Benefited from the synergistic effect of TiO2-sol modified photoanodes and alginate hydrogel (AH)-assisted electrolytes, a champion power conversion efficiency (PCE) of 8.87% for model ZnCuInSe (ZCISe) based QS-QDSCs was achieved with an enhancement of near 10% related to that of the devices based the pristine devices (8.01%), and very close to that of liquid-junction QDSCs (9.06%). Moreover, the constructed QS-QDSCs devices exhibit the excellent stability. This work thus provides a facile and effective strategy to achieve the QS-QDSCs devices with both of high efficiency and good stability.

Translation of traditional medicine is moving away from the reductionist approach towards harnessing the synergy of poly-pharmacological phyto-combinations that modulate the activity of target networks of underlying disease phenotypes. Metabolomics enabled the profiling of herbal extracts and formulations in high resolution through LC-MS/MS, GC-MS and NMR providing the possibility of multi-component drug discovery. Phytopharmaceuticals are multi-molecular combinations which follow a combinatory treatment module which minimizes off-target toxicity by synergistic potency and improve outcomes by synergistic efficacy. Combination synergy is a multi-dimensional concept where synergy can be observed from a network pharmacology perspective. Network pharmacology uses systems-level drug–response phenotypes originating from various ‘omics’ platforms. This network pharmacology with metabolomics has been proven to be effective in elucidating the mechanisms of action of medicinal plants and complex traditional formulations. LC-MS/MS of medicinal plants along with network pharmacology unveil synergistic molecular combinations which interact with neighbouring targets in a combination synergy network. Case studies on some traditional herbs mentioned in Ayurveda, has been reported based on the combination of network-based methods and metabolomics for establishing the mechanism for their therapeutic potentials. The synergistic combination of molecules interacts with target-disease networks which provide novel, mechanistic insights towards understanding their therapeutic potentials. This review along with case-studies illustrates various strategies to explore the mechanism of action for different synergistic natural products combinations through neighbourhood-based network pharmacology approach.

It is well known that high-temperature curing of natural rubber (NR) with a conventional accelerated-sulfur (CV) system is limited because of reversion. This paper describes the curing behavior and the reversion resistance characteristics of unfilled NR with a CV system in the presence of two different bismaleimides: Perkalink 900 (PL) and Maleide F (MF). Rheometer studies reveal that MF can directly interact with the NR during accelerated-sulfur curing and forms some thermally stable bismaleimide type crosslinks in the beginning via Alder-ene reaction. However, even with the use of 4 phr of MF, a considerable reversion was noticed during the curing of NR with CV at 180 °C for 1 hr. A high dosage (5 phr) of MF was therefore required for a complete reversion free plateau type cure pattern. On the other hand, PL has no direct interaction with the NR at the beginning of the curing reaction. Moreover, even 1 phr PL exhibits a marching modulus curing behavior via Diels-Alder reaction. Therefore, to solve the individual issues of these chemicals, a synergistic combination of MF and PL has been identified and applied to facilitate the high-temperature curing of NR/CV devoid of reversion with a plateau type cure pattern.