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Objective: Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor (MAPKi) resistance, which is one of the most common forms of resistance that has emerged in many types of cancers. Here, we aimed to systematically identify the genetic interactions underlying MAPKi resistance, and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance. Methods: We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi, and validated 3 genetic combinations through competitive growth, cell viability, and spheroid formation assays. We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations. We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation, Western blot, qRTPCR, and immunofluorescence assays. Results: We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance (ITGB3 + IGF1R, ITGB3 + JNK, and HDGF + LGR5). We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure. Specifically, we discovered a novel protein complex, HDGF-LGR5, that adaptively responded to MAPKi to enhance cancer cell stemness, which was up- or downregulated by the inhibitors of ITGB3 + JNK or ITGB3 + IGF1R. Conclusions: Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells. ITGB3- + IGF1R-targeting drugs (cilengitide + linsitinib) could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex, which enhanced cancer stemness during MAPKi stress.

The rapid growth of polylactic acid (PLA) production and the slow hydrolysis rate make PLA a potential environmental pollutant. In order to make better reuse of the waste PLA in energy fields and solve the potential pollutant, PLA/wood flour (WF) compounds in all different proportions were co-pyrolyzed to study the co-pyrolysis behavior in terms of energy and products. The apparent activation energy of the 50%wtWF50%wtPLA compounds during co-pyrolysis decreased by 28% than PLA and 29.4% than WF. In addition, the pyrolysis of PLA provided additional energy for the co-pyrolysis of compounds which reduced the external input energy. The chemical reactions between WF and PLA during co-pyrolysis could be called synergistic interactions which promoted the free radical reaction of PLA and lead to the increase of lactide production. The yield of the harmful acetaldehyde reduced by 85.9% in the co-pyrolysis of 25%wtWF75%wtPLA compounds. In addition, the production of small molecular benzene ring substances was increased. For example, the phenol yield increased by 31.3% in the co-pyrolysis of 25%wtWF75%wtPLA compounds. The carbon number distribution of the main products was mainly concentrated on C5–C7 which was better for the reuse of bio-fuels during co-pyrolysis.

The aim of this study is to compare the azole synergy across an insect, Chironomus riparius, and a crustacean species, Daphnia magna. We use a combination of in vivo measurements of cytochrome P450 monooxygenase (CYP) biotransformation potential and toxicokinetic (TK) and toxicodynamic (TD) modeling to understand the mechanism behind the synergy of two azole fungicides: the imidazole prochloraz and the triazole propiconazole on the pyrethroid insecticide α-cypermethrin. For both species, the synergistic effect of prochloraz was well-described by its effect on in vivo CYP activity, which corresponded to the biotransformation rate of the TK model parameterized on the survival data of the mixture experiment. For propiconazole, however, there were 100-fold and 50-fold differences between the 50% effect concentration of in vivo CYP activity and the modeled biotransformation rate for C. riparius and D. magna, respectively. Propiconazole, therefore, seems to induce synergy through a mechanism that cannot be quantified solely by the CYP activity assay used in this study in either of the two species. We discuss the differences between prochloraz and propiconazole as synergists across the two species in the light of the type and time dynamics of affected biotransformation processes.

In this study the effects of iron chloride (FeCl 3 ) on the CO 2 gasification kinetics of lower sulphur petroleum coke (PC) and sugar cane bagasse (SCB) via thermogravimetric analyser (TGA) were investigated. The FeCl 3 loading effects on the thermal behaviour and reactivity of CO 2 gasification of PC were studied. The possible synergistic interaction between the PC and SCB was also examined. Then the homogeneous model or first order chemical reaction (O 1 ) and shrinking core models (SCM) or phase boundary controlled reactions (R 2 and R 3 ) were employed through Coats–Redfern method in order to detect the optimum mechanisms for the catalytic CO 2 gasification, describe the best reaction behaviour and determine the kinetic parameters. The results showed that the thermal behaviour of PC is significantly affected by the FeCl 3 loading. Among various catalyst loadings, the addition of 7 wt% FeCl 3 to PC leads to improve the PC reactivity up to 39% and decrease the activation energy up to 22%. On the other hand, for char gasification stage of SCB and blend, the addition 5 wt% FeCl 3 improved their reactivities to 18.7% and 29.8% and decreased the activation energies to 10% and 17%, respectively. The synergistic interaction between the fuel blend was observed in both reaction stages of the blend and became more significant in the pyrolysis stage. For all samples model R 2 shows the lowest values of activation energy ( E ) and the highest reaction rates constant ( k ). Finally, model R 2 was the most suitable to describe the reactions of non-catalytic and catalytic CO 2 gasification.

Synergetic chemical interaction of various phytochemicals in Amruthotharam kashayam, a polyherbal formulation, has been evaluated by different spectroscopic techniques. Comparative chemical profiling was done along with its ingredient plants by HPTLC analysis. Characterization of major chemical constituents was carried out by Fourier transform infrared spectroscopy (FTIR) and tandem mass spectroscopic analyses (LC/MS-MS). The chromatographic profiling and spectrophotometric studies revealed that the chemistry of the finished formulation is different from that of individual plant extracts. FTIR analysis showed the spectral shift in the formulation when compared with corresponding transmittance in the ingredient plants. The synergetic chemical reaction during the process is evidenced by such specific spectral shift. The tandem mass spectroscopic studies also confirmed the chemical transformations happening during the preparation of Amruthotharam kashayam.

Botrytis cinerea, which causes gray mold disease in more than 200 plant species, is an economically important pathogen that is mainly controlled by synthetic fungicides. Synergistic fungicide mixtures can help reduce fungicide residues in the environment and mitigate the development of fungicide-resistant strains. In this study, we screened microbial culture extracts on Botrytis cinerea to identify an antifungal synergist for tebuconazole. Among the 4,006 microbial extracts screened in this study, the culture extract from Schizophyllum commune displayed the most enhanced activity with a sub-lethal dosage of tebuconazole, and the active ingredient was identified as schizostatin. In combination with 5 μg/ml tebuconazole, schizostatin (1 μg/ml) showed disease control efficacy against gray mold on tomato leaf similar to that achieved with 20 μg/ml tebuconazole treatment alone. Interestingly, schizostatin showed demethylation inhibitor (DMI)-specific synergistic interactions in the crossed-paper strip assay using commercial fungicides. In a checkerboard assay with schizostatin and DMIs, the fractional inhibitory concentration values were 0.0938-0.375. To assess the molecular mechanisms underlying this synergism, the transcription levels of the ergosterol biosynthetic genes were observed in response to DMIs, schizostatin, and their mixtures. Treatment with DMIs increased the erg11 (the target gene of DMI fungicides) expression level 15.4-56.6-fold. However, treatment with a mixture of schizostatin and DMIs evidently reverted erg11 transcription levels to the pre-DMI treatment levels. These results show the potential of schizostatin as a natural antifungal synergist that can reduce the dose of DMIs applied in the field without compromising the disease control efficacy of the fungicides.

Encapsulation in alginate beads has always been limited by the leakage due to the too wide distribution of pore sizes. Mixing alginate with other polymers have sometimes reduced the problem. Hydrocolloids from seven tropical vegetal species (barks of Triumfetta cordifolia and Bridelia thermifolia, seeds of Irvingia gabonensis and Beilschmiedia obscura, and leaves of Ceratotheca sesamoides, Adansonia digitata and Corchorus olitorius) were screened for synergistic interactions with alginate in dilute aqueous solution. Mixtures with alginate were made at different volume proportions and deviations from the initial viscosity set at 1 were evaluated. In distilled water, the gums from T. cordifolia, B. obscura, C. sesamoides and C. olitorius presented synergies with alginate. In 2 mM calcium chloride, the seven gums showed positive synergy. Interactions are favored by gum flexibility and the presence of charges, although high charges reduced the interactions. Alginate fraction of maximum viscosity enhancement depends on the ability to conformational order of the gum. The measure by laser diffraction of alginate-gum particles sizes at different fractions showed that the cooperative interactions did not always involve the largest complexes formed in gums associations. The occurrence of these interactions predicts the formation of homogeneous mixed gels at higher polymer and calcium concentrations., Food Science; Food Technology; Physical Chemistry; Alginate; Calcium Chloride; Synergistic interactions; Tropical vegetal gums.

Genetically engineered crops simultaneously produce defensive allelochemicals and Bacillus thuringiensis (Bt) toxin proteins to kill some of the world's most devastating insect pests. How the two types of toxins, when ingested sequentially or simultaneously, interact at both lethal and sublethal doses in these pests remains underexplored. Here, we examined the toxicological interactions between the Bt toxin Cry1Ac and the flavonoid allelochemical flavone in Helicoverpa armigera. Simultaneous exposure of H. armigera neonates to lethal doses (LC25 ) of Cry1Ac and flavone caused a mortality significantly higher than that of either toxin alone and their expected additive mortality. Preexposure for 24 h to a sublethal dose (LC10 ) of Cry1Ac followed by 6-d simultaneous exposure to the same dose of Cry1Ac plus a lethal dose (1.6 mg/g diets, LC50 ) of flavone resulted in a mortality significantly higher than that of the LC50 dose of flavone alone and the expected additive mortality of the LC50 dose of flavone plus the LC10 dose of Cry1Ac. One-day preexposure to the sublethal dose (LC10 ) of flavone followed by 6-d simultaneous exposure to the LC50 dose (6 ng/cm2 ) of Cry1Ac plus the LC10 dose of flavone yielded a mortality significantly higher than that of the LC50 dose of Cry1Ac but similar to the expected additive mortality of the LC50 dose of Cry1Ac plus the LC10 dose of flavone. The results suggest that Cry1Ac induces and synergizes the toxicity of flavone against H. armigera larvae.

Lightweight yet strong paper with high toughness is desirable especially for impact protection. Herein we demonstrated electrically conductive and mechanically robust paper (AP/PB-GP) made of reduced graphene oxide via interfacial crosslinking with 1-aminopyrene (AP) and 1-pyrenebutyrat (PB) small molecules. The AP/PB-GP with thickness of over ten micrometer delivers a record-high toughness (∼69.67 ± 15.3 MJ m−3 in average), simultaneously with superior strength (close to 1 GPa), allowing an impressive specific penetration energy absorption (∼0.17 MJ kg−1) at high impact velocities when used for ballistic impact protection. Detailed interfacial and structural analysis reveals that the reinforcement is synergistically determined by π-π interaction and H-bonding linkage between adjacent graphene lamellae. Especially, the defective pores within the graphene platelets benefit the favorable adsorption of the pyrene-containing molecules, which imperatively maximizes the interfacial binding, facilitating deflecting crack and plastic deformation under loading. Density functional theory simulation suggests that the coupling between the polar functional groups, e.g., −COOH, at the edges of graphene platelets and −NH2 and −COOH of AP/PB are critical to the formation of hydrogen bonding network.

Microalgae, as the most promising raw material for biodiesel, can absorb and transform N, P, and organic matter in wastewater into cell components such as oil, carbohydrate, and protein. The cultivation of microalgae in wastewater provides the possibility to realize harmless treatment and resource utilization of wastewater and reduce the cost of microalgal culture. Whether in a single microalgal culture process or wastewater system, there always be a large number of bacteria interacting with microalgae, forming a complex microecological system. Although microalgal–bacterial coculture system is feasible features for the higher biomass production and better nutrient adaptability from wastewater, the precise understanding of interaction and coexistence in water bodies is still unclear. Some major challenges are to develop sustainability in the microalgal–bacterial coculture system due to the incomplete knowledge about the mechanism of communication, algal growth promotion, and effect of microalgae on the indigenous bacteria in wastewater. In the present review, nutritional interaction and signal transduction, two main interaction models of algae and bacteria, and the effect of synergism of these two models on microalgal system are summarized. Moreover, the impact of algal–bacterial coculture on algal growth and removal of pollutants in wastewater treatment process was expounded systematically to develop highly efficient consortium systems by covering the sustainability limitations. This work would provide guidance for the establishment of efficient algal–bacterial symbiosis system in the wastewater with complex microecology and nutrient environment to improve the accumulation of microalgal biomass and reduce the cost of microalgal culture.

For photocatalytic CO2 reduction, the synergistic effect of Lewis acidity and basicity on CO2 activation is worthy of study. On the basis of a large number of oxygen defects (Lewis acidity) and hyd...

Interactions among antiwear additives (AWs), friction modifiers (FMs), and dispersant in a lubricating oil are critical for tribological performance. This study investigates compatibilities of three oil-soluble ionic liquids (ILs, candidate AWs) with an FM, molybdenum dithiocarbamate (MoDTC), and a dispersant, polyisobutene succinimide (PIBSI) under boundary lubrication. Either synergistic or antagonistic effects were observed depending on the IL's chemistry. Adding an aprotic phosphonium-alkylphosphate or phosphonium-alkylphosphinate IL into the oil containing MoDTC and PIBSI had detrimental impact on the friction and wear behavior. PIBSI was found to preferably interact/react with the aprotic IL to lose its ability of suspending MoDTC and to partially consume or even deplete the IL. In contrast, a protic ammonium-alkylphosphate IL seemed to be able to coexist with PIBSI and work synergistically with MoDTC, yielding a sustainable, ultralow boundary friction. A three-stage tribochemical process is proposed to explain how this IL + MoDTC pair interacts with the contact surface to form a chemically reacted, wear-protective tribofilm supporting a physically adsorbed, friction-reducing film on top. This study provides fundamental insights of the compatibilities among three common lubricant components, antiwear, friction modifier, and dispersant, which can be used to guide future lubricant development.

Cel48A of Thermobifida fusca (TfCel48A) is a processive exocellulase that contains an active site tunnel and digests lignocellulosic biomass via synergistic interactions between different cellulases. Cel48A possesses a number of aromatic amino acids lining the tunnel entrance, which are highly conserved across a diverse number of microbial species and appear to play a role in the selection and threading of individual strands of cellulose from highly recalcitrant substrates. In this study, we sought to further elucidate the roles of these tunnel entrance aromatic amino acids by creating a series of double mutants and examining their effect on TfCel48A activity, processivity, and synergistic interactions with the well-studied processive endocellulase TfCel9A. Our results provide further insight concerning the mechanism of Cel48A kinetics with soluble and insoluble substrates and could play an influential role in the application of Cel48A and other exocellulases for industrial purposes.

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of CBD and its synergistic combination with SN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.

Due to biological safety and negligible toxicity, nitric oxide (NO) therapy has gained increasing interest in the field of cancer therapy during the past few years. However, individual NO cancer therapy normally exhibited limited therapeutic efficiency. In order to acquire satisfactory therapeutic outcomes, the NO therapy is usually combined with other therapeutic treatments, mostly chemotherapy. Herein, we constructed HA-TPP@NORM nanoparticles based on the co-assembly of an NO donor (NORM) and tetraphenylporphyrin (TPP)-modified hyaluronic acid, which can efficiently generate a highly biocidal molecule of peroxynitrite (ONOO−) via the synergistic interactions of the nitric oxide (NO) therapy and photodynamic therapy (PDT) to enhance the cancer therapeutic efficiency. In addition, MTT results exhibited that without light irradiation, the HA-TPP@NORM nanoparticles have favourable biocompatibility with the cell viability above 95% at the maximum TPP concentration (20 μg mL−1). Under simultaneous irradiation with 365 nm and 650 nm light, ONOO− can be efficiently produced in cancer cells via the direct coupling reaction of the generated NO and superoxide anion radical (O2˙−), which significantly enhanced the anticancer effect, when compared with individual NO therapy or PDT therapy. Therefore, the HA-TPP@NORM nanoparticles may provide a new insight into the design of efficiently NO-related cancer therapeutic systems.

Biophysical and structural studies of peptide–lipid interactions, peptide topology and dynamics have changed our view of how antimicrobial peptides insert and interact with membranes. Clearly, both peptides and lipids are highly dynamic, and change and mutually adapt their conformation, membrane penetration and detailed morphology on a local and a global level. As a consequence, peptides and lipids can form a wide variety of supramolecular assemblies in which the more hydrophobic sequences preferentially, but not exclusively, adopt transmembrane alignments and have the potential to form oligomeric structures similar to those suggested by the transmembrane helical bundle model. In contrast, charged amphipathic sequences tend to stay intercalated at the membrane interface. Although the membranes are soft and can adapt, at increasing peptide density they cause pronounced disruptions of the phospholipid fatty acyl packing. At even higher local or global concentrations the peptides cause transient membrane openings, rupture and ultimately lysis. Interestingly, mixtures of peptides such as magainin 2 and PGLa, which are stored and secreted naturally as a cocktail, exhibit considerably enhanced antimicrobial activities when investigated together in antimicrobial assays and also in pore forming experiments applied to biophysical model systems. Our most recent investigations reveal that these peptides do not form stable complexes but act by specific lipid-mediated interactions and the nanoscale properties of phospholipid bilayers.

A series of HPW/Zn-Ti layered double hydroxides (LDHs) were prepared by immobilizing phosphotungstic acid (HPW) on the Zn-Ti LDHs. Systematically characterizations were performed to elucidate their structure. These HPW/Zn-Ti LDHs hybrids were used as heterogeneous catalysts in the epoxidation of fatty acid methyl ester (FAMEs) with H2O2. The HPW/Zn-Ti LDHs showed higher activity than bulk HPW and Zn-Ti LDHs. The conversion of FAMEs and the selectivity to epoxy fatty acid methyl ester (EFAME) were up to 90.6 and 86.0%, respectively. (PO4[WO2(O2)]4)3- was presumed to be the active site for the epoxidation in this work. The formed oxygen-donating intermediate Ti-OOH transferred oxygen free radicals to (PO4[WO2(O2)]4)3- in the catalytic process, accelerating the transfer of oxygen free radicals. Therefore, high catalytic activity of HPW/Zn-Ti LDHs is related to the potential synergistic interactions of Ti-OOH and PW anions.

Background Mortality rate of invasive Candida infections is raising mainly amongst immunocompromised patients. These infections are hard-to-treat mainly due to the increasing incidence of resistance. The overexpression of ATP-binding cassette and major facilitator superfamily transporters is the main responsible for the failure of antifungal therapies. In a Saccharomyces cerevisiae model, β-lapachone inhibited Pdr5p, a transporter homologous to those found in Candida albicans. Aims To determine whether β-lapachone reverses the resistance phenotype mediated by efflux transporters in C. albicans clinical isolates. Methods The antifungal activity of β-lapachone combined with fluconazole was measured by agarose chemosensitization and microdilution assays. CaCdr2p and CaMdr1p activities were evaluated through fluorescent dyes accumulation. ATPase activity was assessed using transporter-enriched plasma membranes. Results β-lapachone reverted antifungal resistance of S. cerevisiae and C. albicans strains overexpressing CaCdr2p and CaMdr1p transporters by inhibiting these proteins activities. CaCdr2p ATPase activity was not impaired by the compound. Conclusions β-lapachone is a promising drug candidate to be used as an adjuvant in the treatment of candidiasis caused by fluconazole-resistant C. albicans strains.

Random peptide mixtures (RPMs) have been recently proposed as powerful antimicrobial compounds. These are unique mixtures of peptides synthesized by random combination of a cationic and a hydrophobic amino acid. Here, we introduce a new type of antimicrobial compounds, short lipo-RPMs, which result from N-palmitoylation of RPMs. We report the characterization of 5-mer lipo-RPMs containing l-phenylalanine and d-lysine, named p-FdK5. p-FdK5 had high antibacterial activity against several bacterial strains and was able to reduce disease severity caused by a plant pathogen. We further synthesized and studied all 32 (25) possible lipopeptides that compose the p-FdK5 mixture. We showed that the antibacterial activity of specific lipopeptides depends on the peptide hydrophobicity and on the location of the hydrophobic amino acids relative to the palmitic acid. Interestingly, synergism assays revealed positive interactions between different sequence-specific lipopeptides in terms of antimicrobial activity.

Farnaz Minooei,1 Joel R Fried,1 Joshua L Fuqua,2– 4 Kenneth E Palmer,3– 5 Jill M Steinbach-Rankins2– 5 1Department of Chemical Engineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 2Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 3Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA; 4Center for Predictive Medicine, University of Louisville, Louisville, KY, USA; 5Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USACorrespondence: Jill M Steinbach-RankinsDepartment of Bioengineering, University of Louisville Speed School of Engineering, 505 S. Hancock St., Room 623, Louisville, KY, 40202, USATel +1 502-852-5486Email jmstei01@louisville.eduIntroduction: Human immunodeficiency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1. While ARV co-administration has been shown to enhance virus inhibition, synergistic interactions between ARVs and the oxidation-resistant variant of GRFT (Q-GRFT) have not yet been explored. Here, we co-administered Q-GRFT with TFV, RAL, and DAP, in free and encapsulated forms, to identify unique protein-drug synergies.Methods: Nanoparticles (NPs) were synthesized using a single or double-emulsion technique and release from each formulation was assessed in simulated vaginal fluid. Next, each ARV, in free and encapsulated forms, was co-administered with Q-GRFT or Q-GRFT NPs to evaluate the impact of co-administration in HIV-1 pseudovirus assays, and the combination indices were calculated to identify synergistic interactions. Using the most synergistic formulations, we investigated the effect of agent incorporation in NP-fiber composites on release properties. Finally, NP safety was assessed in vitro using MTT assay.Results: All active agents were encapsulated in NPs with desirable encapsulation efficiency (15– 100%), providing ∼ 20% release over 2 weeks. The co-administration of free Q-GRFT with each free ARV resulted in strong synergistic interactions, relative to each agent alone. Similarly, Q-GRFT NP and ARV NP co-administration resulted in synergy across all formulations, with the most potent interactions between encapsulated Q-GRFT and DAP. Furthermore, the incorporation of Q-GRFT and DAP in NP-fiber composites resulted in burst release of DAP and Q-GRFT with a second phase of Q-GRFT release. Finally, all NP formulations exhibited safety in vitro.Conclusions: This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis.Keywords: griffithsin, nanoparticles, electrospun fibers, antiretrovirals, synergy, HIV-1 prevention, microbicide

The mechanical and barrier properties of plant-based enteric polymer films were enhanced by synergistic interactions between binary gum mixtures and adding plasticizers. The results indicated that the best ratio of gellan gum (GG) and xanthan gum (XG) was 7:3 by comparing tensile strength, tensile elongation, transmittance, and water vapor permeability of plant-based enteric polymer films and rheological properties of solutions. Polyethylene glycol 400 (PEG-400) was an effective plasticizer in improving plasticity and water vapor barrier property of the plant-based enteric polymer film. Rheology measurement and different characterization methods, including Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy, were used to explain interactions between GG and XG as well as PEG-400 and components of the film. The new mixed system, composed of GG/XG mixture with ratio of 7:3 as a novel gelling agent and PEG-400 as a plasticizer, was applied to prepare plant-based enteric hard capsules, which have potential applications in medicines and functional food preparations.

The biotechnological application of microorganisms for rhizoremediation of contaminated sites requires the development of plant-microbe symbionts capable of plant growth promotion and hydrocarbon degradation. Studies focusing on microbial consortia are often difficult to reproduce, thereby necessitating the need for culturable single bacterial species for biotechnological applications. Through genomic analyses and plant growth experiments, we examined the synergistic interactions ofMedicago sativaL. andParaburkholderia tropicafor enhanced remediation of diesel fuel-contaminated soils. Comparative genomics revealed strong potential ofP. tropicafor plant growth-promotion, chemotaxis and motility, root nodulation and colonization, and diesel fuel degradation. Plant growth experiments confirmed thatP. tropicathrived in the contaminated soils and effectively enhancedM. sativagrowth. Geochemical analysis showed that theM. sativa+P. tropicatreatment resulted in an efficient degradation of diesel fuel hydrocarbons within two months, offering great prospects for enhanced biodegradation of organic pollutants.

The reactivity and functionality of nanoparticles (NPs) are determined by the material- and size-dependent physicochemical properties at nanoscale. While single-type metallic NPs have been extensiv...

Interactions between multiple functional groups are key to catalysis. Previously, we reported synergistic interactions in catalytic amyloids formed by mixtures of heptameric peptides that lead to significant improvements in esterase activity. Herein, we describe the in-depth investigation of synergistic interactions within a family of amyloid fibrils, exploring the results of functional group interactions, the effects of chirality and the use of mixed enantiomers within fibrils. Remarkably, we find that synergistic interactions (either positive or negative) are found in the vast majority of binary mixtures of catalytic amyloid-forming peptides. The productive arrangements of functionalities rapidly identified by mixing different peptides will undoubtedly lead to the development of more active catalysts for a variety of different transformations.

The interactions between six commonly occurring fungal species in damp or water-damaged houses in southern California were studied. These fungal species were Alternaria alternata, Aspergillus niger, Chaetomium globosum, Cladosporium herbarum, Penicillium chrysogenum and Stachybotrys chartarum. In the damp building materials, S. chartarum was found to be associated with A. niger, C. globosum, and P. chrysogenum but not with A. alternata and C. herbarum. Stachybotrys chartarum showed strong antagonistic effect against A. alternata and C. herbarum and significantly inhibited in vitro growth of A. alternata and C. herbarum but had no effect on A. niger, C. globosum, and P. chrysogenum. Two trichothecenes, produced by S. chartarum, trichodermin and trichodermol, significantly inhibited spore germination and in vitro growth of A. alternata and C. herbarum but had no effect on A. niger, C. globosum, P. chrysogenum and S. chartarum. In the damp building materials (drywall, ceiling tile, and oak woods), S. chartarum significantly inhibited the growth of A. alternata and C. herbarum and had no effect on the growth and colonization of A. niger, C. globosum, P. chrysogenum in these substrata.

It is possible that Pickering emulsions can optimize the transport of nutraceuticals, pharmaceuticals, and other bioactive compounds in human physiology. So-called ultrastable Pickering emulsions are often destabilized in the gastric digestion regime if the particles are proteinaceous in nature. The present study seeks to test how the interfacial structure can be engineered via synergistic particle-particle interactions to impact the gastric coalescence of Pickering emulsions. In this study, we designed plant-based protein-particle-stabilized oil-in-water emulsions (PPM-E, with 20 wt % sunflower oil) via pea protein microgels (PPM at 1 wt %). The PPM hydrodynamic diameter is ∼250 nm. In vitro gastric digestion of PPM-E confirmed droplet coalescence within 30 min of pepsin addition. Supposedly surface-active cellulose nanocrystals (CNCs, 1-3 wt %) were added to PPM-E at pH 3.0 to determine if they could act as a barrier to interfacial pepsinolysis due to the CNC and PPM being oppositely charged at this gastric pH value. A combination of confocal microscopy, zeta potential, and Langmuir trough measurements suggested that CNCs and PPMs might form a combined layer at the O/W interface, owing to the electrostatic attraction between them. CNCs at >2 wt % inhibited the pepsinolyis of the adsorbed PPM film and thus droplet coalescence. However, increasing concentrations of CNC also increased the bulk viscosity of the PPM-E and eventually caused gelation of the emulsions, which would also delay their gastric breakdown. In conclusion, tuning the bulk and interfacial structure of Pickering emulsions via synergistic interactions between two types of particles could be an effective strategy to modify the enzymatic breakdown of such emulsions, which would have important applications in pharmaceuticals, foods, and other soft-matter applications.

A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. Retinoic acid (RA), a vitamin A derivative, is a promising agent that can induce differentiation in NB cells. Its isoform, 13-cis RA or isotretinoin, is used in NB therapy; however, its effectiveness is limited to treating a minimal residual disease as maintenance therapy. As such, research focuses on RA derivatives that might increase the anti-NB action or explores the potential synergy between RA and other classes of drugs, such as cellular processes mediators, epigenetic modifiers, and immune modulators. This review summarises the in vitro, in vivo, and clinical data of RA, its derivatives, and synergising compounds, thereby establishing the most promising RA derivatives and combinations of RA for further investigation.

Background: The combination effect of 5-fluorouracil (5-FU) with either CX-4945 or a new inhibitor of protein kinase CK2, namely 14B (4,5,6,7-tetrabromo-1-(3-bromopropyl)-2-methyl-1H-benzimidazole), on the viability of MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines was studied. Methods: Combination index (CI) values were determined using an MTT-based assay and the Chou-Talalay model. The effect of the tested drug combinations on pro-apoptotic properties and cell cycle progression was examined using flow cytometry. The activation of FAK, p38 MAPK, and ERK1/2 kinases and the expression of selected pro-apoptotic markers in MDA-MB-231 cell line after the combined treatment were evaluated by the western blot method. Confocal microscopy was used to examine actin network in MDA-MB-231. Results: Our results showed that a synergistic effect (CI &lt, 1) occurred in MDA-MB-231 after treatment with both combinations of 5-FU with 14B or CX-4945, whereas the combination of 5-FU and 14B evoked an antagonistic effect in MCF-7. We conclude that the synergistic interactions (CI &lt, 1) observed for both the combinations of 5-FU and 14B or CX-4945 in MDA-MB-231 correlated with an activation of p38 MAPK, inhibition of FAK, increased expression of apoptogenic markers, prolongation of S-phase of cell cycle, and destabilization of actin network. Conclusions: The obtained results support the recent observation that CK2 inhibitors can improve 5-FU-based anticancer therapy and FAK kinase can be an attractive molecular target in breast cancer therapy.

With a steady growth in use of engineered nanoparticles (NPs) in consumer products the unintended exposure to humans has increased. The risks associated with introduction of NPs in the environment have been widely investigated, but mostly for single type of NPs. Herein, a single NP and NP co-exposure study is reported: the cellular effects of silver and platinum NPs on the main components of the blood–brain barrier, human cerebral microvascular endothelial cells, and human primary astrocytes. The synergy is quantitatively evaluated as per the Chou–Talalay method. NP co-exposure synergistically inhibits proliferation of both cell types, to a greater extent for endothelial cells. In addition, astrocytes are more tolerant to NPs. The mechanism of synergy with short-duration incubation time points (up to 30 min) is further explored. Although intracellular trafficking studies and quantitative assessments of NP uptake does not explain the mechanisms of synergistic cytotoxicity, a proteomics analysis suggests that it arises from activation of an immune modulating response and deregulation of the extracellular matrix organization. The substantial synergetic effects in the co-exposure studies highlight the importance of this work in relation to assessment of the health risks associated with nanomaterials.

The limited therapeutic options and the recent emergence of multidrug-resistant Candida species present a significant challenge to human medicine and underscore the need for novel therapeutic approaches. Drug repurposing appears as a promising tool to augment the activity of current azole antifungals, especially against multidrug-resistant Candida auris. In this study, we evaluated the fluconazole chemosensitization activities of 1,547 FDA-approved drugs and clinical molecules against azole-resistant C. auris. This led to the discovery that lopinavir, an HIV protease inhibitor, is a potent agent capable of sensitizing C. auris to the effect of azole antifungals. At a therapeutically achievable concentration, lopinavir exhibited potent synergistic interactions with azole drugs, particularly with itraconazole against C. auris (fractional inhibitory concentration index [ΣFICI] ranged from 0.04 to 0.09). Additionally, the lopinavir/itraconazole combination enhanced the survival rate of C. auris-infected Caenorhabditis elegans by 90% and reduced the fungal burden in infected nematodes by 88.5% (P

The reaction parameters including catalyst dosage, oxidant amount, initial contaminant concentration and pH etc. play the crucial roles in the heterogeneous persulfate oxidation processes, while the synergistic interactions among these reaction parameters are still obscure. We herein took an efficient heterogeneous persulfate oxidation system “bimetallic MnxCo3−xO4 solid solution (MnCo) activated peroxymonosulfate (PMS)” for carbamazepine (CBZ) removal from water. MnCo/PMS system exhibited outstanding performance that CBZ was completely removed within 10 min. The CBZ degradation performance was ascribed to the radical oxidation of SO4·- and O2·-, the nonradical oxidation of 1O2, the redox cycles between Mn and Co species and synergistic interactions among MnCo, PMS and CBZ. By monotonously or synchronously adjusting the MnCo dosage, PMS amount and initial CBZ concentration, the inherent connections of different reaction parameters were established. Strong and different synergistic interactions between MnCo and PMS, and among MnCo, PMS and CBZ, were existed due to the formation of three different reaction modes when reaction parameters met certain conditions. The features of the modes were “two-stage, the following auto-deceleration”, “one-stage, constant velocity” and “two-stage, the following auto-acceleration”. This discovery may provide new insights into the synergistic interactions of reaction parameters in advanced oxidation processes for wastewater treatment.

Candida auris is an emerging multidrug-resistant pathogen implicated in numerous outbreaks worldwide, with a notably high mortality rate (ca. 60%). A significant challenge with treatment of these infections is the resistance of C. auris to most antifungal drugs used clinically. Thus, finding co-drugs capable of overcoming resistance to frontline antifungals is of prime clinical importance. In this study, the ability of the combination of different sulfa drugs with azole antifungals to inhibit the growth of azole-resistant C. auris isolates was evaluated. Among the active sulfa drugs, sulfamethoxazole exhibited the most potent in vitro synergistic interactions with voriconazole and itraconazole. The sulfamethoxazole-voriconazole combination restored voriconazole's fungistatic activity against three of eight voriconazole-resistant clinical isolates. Similarly, the sulfamethoxazole-itraconazole combination restored itraconazole's fungistatic activity against three of four itraconazole-resistant clinical isolates. This activity was further confirmed in vivo in a Caenorhabditis elegans model of C. auris infection. The sulfamethoxazole-voriconazole combination enhanced survival of nematodes infected with C. auris by nearly 70%. Notably, these data indicate that the efficacy of this novel combination is dependent on the underlying mechanism of azole resistance. Mutant strains demonstrating azole resistance by either overproduction of or decreased affinity for the azole target (ERG11p) were found highly to be susceptible to the sulfamethoxazole-azole combination. However, this synergistic interaction was ineffective against mutant strains that demonstrated azole resistance via efflux pump hyperactivity. In conclusion, sulfamethoxazole represents a promising co-drug that can restore the efficacy of certain azole antifungal drugs against some azole-resistant isolates of C. auris.

The main reasons for the discontinuation of contact lens wear are ocular dryness and discomfort. Proteoglycan 4 (PRG4), a mucinous glycoprotein, and hyaluronic acid (HA), a nonsulfated linear glycosaminoglycan, are naturally present in the eye and contribute to ocular hydration and lubrication. This study aimed to investigate the impact of the structure of the recombinant human PRG4 (rhPRG4)/HA complex on contact lens properties, when one agent is grafted and the counterpart is physisorbed on the surface of model conventional or silicone contact lens materials. Investigation of the wettability, water retention, antifouling, and boundary lubricant properties of the prepared hydrogels showed that the rhPRG4/HA interactions varied with the rhPRG/HA configuration on the hydrogel surface as well as the composition of the underlying substrate used. The rhPRG4-physisorbed/HA-grafted sample was characterized by better antifouling and boundary lubricant properties on the model conventional hydrogels, while the HA-physisorbed/rhPRG4-grafted sample exhibited improved surface wettability, antifouling, and water-retentive properties on the model silicone hydrogels. The results of this study contribute to the design of biomimetic contact lens surfaces that work synergistically with ocular fluid-phase biological agents to enhance compatibility between the contact lens and the ocular environment, alleviating dry eye symptoms and improving comfort.

The fusion of different electroactive components of lithium-ion batteries (LIBs) sometimes brings exceptional electrochemical properties. We herein report the reduced graphene-oxide (rGO)-coated Zn2SnO4z@NiO nanofibers (ZSO@NiO@G NFs) formed by the synergistic fusion of three different electroactive components including ZnO, SnO2, and NiO that exhibit exceptional electrochemical properties as negative electrodes for LIBs. The simple synthetic route comprised of electrospinning and calcination processes enables to form porous one-dimensional (1D) structured ZSO, which is the atomic combination between ZnO and SnO2, exhibiting effective strain relaxation during battery operation. Furthermore, the catalytic effect of Ni converted from the surface-functional NiO nanolayer on ZSO significantly contributes to improved reversible capacity. Finally, rGO sheets formed on the surface of ZSO@NiO NFs enable to construct electrically conductive path as well as a stable SEI layer, resulting in excellent electrochemical performances. Especially, exceptional cycle lifespan of more than 1600 cycles with a high capacity (1060 mAh g-1) at a high current density (1000 mA g-1), which is the best result among mixed transition metal oxide (stannates, molybdates, cobaltates, ferrites, and manganates) negative electrodes for LIBs, is demonstrated.

The abundance of toxic heavy metals, organic and inorganic pollutants, xenobiotic chemicals and contaminants pose a major threat to the environment which is linked to the health of the living systems including human beings and needs an eco-friendly remediation technology. This technology may not only reduce the pollution level by degradation or detoxification of such hazardous pollutants but also does not generate any secondary or intermediate pollutants. Phytoremediation is an advanced and efficient plant-based treatment technology that takes advantage of the remarkable ability of the plants to tolerate and grow at higher concentration of pollutants/contaminants. The mechanisms used by the plants for the removal of toxic components from the surroundings include accumulation, absorption or transformation of the toxic compounds in their tissues, leaf, stem and roots. In addition to this, plant-associated microbes also play an important role to enhance the efficiency of phytoremediation process. In recent years, understanding the knowledge of the synergistic relationship between plants and microbes for the removal of unwanted chemicals becomes an interesting area of research. Understanding the physiological and molecular mechanisms of plant–microbe interaction helps the environmentalists to get an insight of this technology and to improve and expand new horizons of phytoremediation.

Materials based on petroleum-based resources have aroused widespread concern because of their environmental and healthcare footprints. Cellulose nanocrystals (CNCs) are at the cutting edge of current research because of their great promise in developing sustainable and high-performance materials. To establish a comprehensive understanding of the synergistic reinforcement effect of CNCs, we introduced a new method to fabricate all-green, transparent, and mechanically robust nanohybrid materials using CNCs in conjunction with gelatinized starch (GS) and polyhydroxyurethanes (PHUs). The synergistic interaction between the CNC skeleton and the GS/PHU network enabled us to span exceptionally stiff nanohybrids that could withstand up to 8.5 MPa tensile strength. The tunable mechanical properties and enhanced thermal stability in these nanohybrids primarily arise from the presence of dense hydroxyl groups on the CNCs' surface, which offer a robust scaffold for fortified hydrogen bonds to form with GS/PHU domains. The multiple intramolecular hydrogen bonds synergistically served as highly stable associations and concurrently facilitated energy dissipation and transferred the stress across the interfacial region. The rational design of the molecular interactions presented in this work provided increased opportunities to build nanohybrids with outstanding mechanical performance. More broadly, the insights afforded by this study not only delivered a better understanding on the molecular-level interactions in the CNC/GS/PHU system but also enriched the potential for the commercial exploration of tunable cellulosic nanohybrid materials.

The self-assembly of short peptides into catalytic amyloid-like nanomaterials has proven to be a powerful tool in both understanding the evolution of early proteins and identifying new catalysts for practically useful chemical reactions. Here we demonstrate that both parallel and antiparallel arrangements of β-sheets can accommodate metal ions in catalytically productive coordination environments. Moreover, synergistic relationships, identified in catalytic amyloid mixtures, can be captured in macrocyclic and sheet-loop-sheet species, that offer faster rates of assembly and provide more complex asymmetric arrangements of functional groups, thus paving the way for future designs of amyloid-like catalytic proteins. Our findings show how initial catalytic activity in amyloid assemblies can be propagated and improved in more-complex molecules, providing another link in a complex evolutionary chain between short, potentially abiotically produced peptides and modern-day enzymes.

Microbial sulfate-reduction coupling polycyclic aromatic hydrocarbon (PAH) degradation is an important process for the remediation of contaminated sediments. However, little is known about core players and their mechanisms in this process due to the complexity of PAH degradation and the large number of microorganisms involved. Here we analyzed potential core players in a black-odorous sediment using gradient-dilution culturing, isolation and genomic/metagenomic approaches. Along the dilution gradient, microbial PAH degradation and sulfate consumption were not decreased, and even a significant (p = 0.003) increase was observed in the degradation of phenanthrene although the microbial diversity declined. Two species, affiliated with Desulfovibrio and Petrimonas, were commonly present in all of the gradients as keystone taxa and showed as the dominant microorganisms in the single colony (SB8) isolated from the highest dilution culture with 93.49% and 4.73% of the microbial community, respectively. Desulfovibrio sp. SB8 and Petrimonas sp. SB8 could serve together as core players for sulfate-reduction coupling PAH degradation, in which Desulfovibrio sp. SB8 could degrade PAHs to hexahydro-2-naphthoyl through the carboxylation pathway while Petrimonas sp. SB8 might degrade intermediate metabolites of PAHs. This study provides new insights into the microbial sulfate-reduction coupling PAH degradation in black-odorous sediments.

Summary Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model., Graphical Abstract, Highlights • 1-alkyl-3-methylimidazolium RTILs have antimicrobial properties • Alkyl chain length correlates with lethality and permeability • Combinations of RTIL + antimicrobial enhance antimicrobial effects • Combinatorial effect is not evident in human cell lines, Chemistry; Biological Sciences; Biochemistry; Microbiology; Biophysics

Cadmium-free quantum dots (QD) were combined with crystal violet photosensitising dye and incorporated into medical grade polyurethane via a non-covalent dipping process known as ‘swell-encapsulation-shrink’. The antibacterial efficacy of the prepared quantum dot-crystal violet polyurethane substrates (QD + CV PU) was investigated under low power visible light illumination at similar intensities (500 lux) to those present in clinical settings. The antibacterial performance of QD + CV PU was superior to the constituent polymer substrates, eliminating ∼99.9% of an environmental P. aeruginosa strain, a clinical P. aeruginosa strain from a cystic fibrosis patient and a clinical E. coli strain. The nature of the reactive oxygen species (ROS) involved in antibacterial activity of the QD + CV PU surface was investigated using ROS inhibitors and time-resolved optical spectroscopy. The photo-physical interactions of the green-emitting QDs with CV lead to a combination of Type I and II electron transfer and energy transfer processes, with the highly potent ROS singlet oxygen playing a dominant role. This study is the first to demonstrate highly efficient synergistic killing of clinical and environmental strains of intrinsically resistant and multi-drug resistant Gram-negative bacteria using light-activated surfaces containing biocompatible cadmium-free QDs and crystal violet dye at ambient light levels.

Submerged macrophyte Vallisneria spiralis and sediment microbial fuel cell (SMFC) systems are cost-effective methods for the remediation of polycyclic aromatic hydrocarbon (PAH)–polluted sediments. This study evaluates whether the combination of these two ecological approaches could further improve the removal efficiency of PAHs from sediments and investigates the possible mechanisms of removal. Sediments, macrophytes, electrodes, and plexiglass columns were used to construct an experimental microcosm. A 65-day comparative study was performed with six treatments as follows: SMFC without PAH (SMFC); PAH only (PAH); SMFC with PAH (SMFC-PAH); V. spiralis without PAH (macrophyte); V. spiralis with PAH (macrophyte-PAH); V. spiralis with SMFC and PAH (M-SMFC-PAH). Pyrene and phenanthrene were added to raw sediments to obtain initial PAH concentrations of 10 mg kg−1 dry sediment. The monitored parameters were sediment oxidation–reduction potential (ORP); low molecular weight organic acids (LMWOAs) and Fe (II) concentrations in pore water; electron acceptor (sulfate and Fe (III)), humic acid (HA), and PAH concentrations in sediments; and plant morphology and root physiology. High-throughput 16S rRNA gene sequencing was also performed to assist mechanistic understanding. The M-SMFC-PAH treatment obtained the highest sediment ORP and PAH removal efficiency. The average ORP level in M-SMFC-PAH was increased by 57.2, 59.1, and 168.4 mV, compared with the SMFC-PAH, macrophyte-PAH, and PAH-only treatments, respectively, with a mean value of 121.7 mV observed during the whole experimental period. The pyrene (phenanthrene) dissipation ratios at the end of the experimental period were 29.1% (35.4%), 45.5% (56.3%), 59.8% (67.3%), and 79.4% (88.2%) for PAH only, SMFC-PAH, macrophyte-PAH, and M-SMFC-PAH treatments, respectively. The highest correlation was observed between PAH concentration and sediment ORP value, in the coupled M-SMFC-PAH system. Results suggest that the interactions between the anode and rhizosphere of V. spiralis were synergistic during PAH removal. The coexistence of anodic and rhizospheric oxygen loss in sediments had a synergistic effect on PAH degradation. Plant presence facilitated the electrogenic degradation of PAHs. The inhibited growth of V. spiralis due to PAH toxicity was reduced by electrogenesis, thus facilitating the removal of vegetable PAHs from sediments. Coordinated growth of anaerobic and aerobic PAH degrading bacteria on the anode was a key factor in the optimal removal of PAHs in coupled systems.

Objective Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol (CAT) and stachyose (STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes. Methods Streptozotocin (STZ) with the feeding of high-sugar-high-fat diet (HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medical-treated groups: metformin (MET), STA, CAT, and three combinations of CAT:STA (1:1, 1:2, 2:1). Blood, liver, and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues. Results It turned out that CAT, STA and their three combinations (1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c, TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine (Ucr). However, there were no such consistent observations on serum creatinine (Scr) and creatinine clearance rate (Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications, compared to the sole CAT or STA treatment. Conclusion Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.

Equivalent donor and acceptor tendencies in DESs bring strong synergistic interaction into play and result in high CO2 uptake by lowering the ΔH° and ΔS°.

An understanding of the inter-species relationships, especially their metabolic network in a mixed-culture system, is crucial to design an effective inoculum for enhancing the power generation of wastewater fed microbial fuel cell (MFC). In the present study, the influence of microbial mutualistic interactions on the power generation of palm oil mill effluent fed MFCs has been widely investigated by designing several co-culture and mixed culture inoculums. Among the different inoculum compositions, the highest power density of 14.8 W/m3 was achieved by Pseudomonas aeruginosa and Klebsiella variicola co-culture inoculum due to their synergistic relationships which were inter-linked via fermentation-based metabolites. Besides, the interaction of K. variicola and Bacillus cereus positively influenced the power generation resulting in a maximum power density of 11.8 W/m3 whereas the antagonistic relationship between B. cereus and P. aeruginosa resulted in a lower power generation of 1.9 W/m3. The microbial mutualistic interactions were investigated with polarization, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), as well as by using metabolite and biofilm analysis. It was observed that the synergism between bacteria enhanced power generation through the production of higher electron shuttling mediators and efficient biofilm formation as evidenced by polarization, CV and EIS analysis. In contrast, the antagonistic relationship resulted in production of cell inhibiting metabolites leading to the formation of ineffective biofilm. These findings demonstrate that the synergistic interaction between or within microorganisms is emergent in designing co-culture or mixed-culture inoculum for achieving maximum power generation in MFCs.