Significant Synergistic Effect Research Articles

Synergistic potential of teriflunomide with fluconazole against resistant Candida albicans in vitro and in vivo.

Candida albicans is the primary cause of systemic candidiasis, which is involved in high morbidity and mortality. Drug resistance exacerbates these problems. In addition, there are limited antifungal drugs available. In order to solve these problems, combination therapy has aroused great interest. Teriflunomide is an immunosuppressant. In the present work, we aimed to identify whether teriflunomide can reverse the resistance of Candida albicans in the presence of sub-inhibitory concentrations of fluconazole in vitro and in vivo. Seven Candida albicans isolates were used in this study. Susceptibility of Candida albicans in vitro to the drugs was determined using a checkerboard microdilution assay in accordance with the recommendations of the Clinical and Laboratory Standards Institute. The effects of drugs on biofilm biomass of Candida albicans were determined by crystal violet staining. The development ability of Candida albicans hyphae was performed using a modified broth microdilution method. Galleria mellonella was used for testing the in vivo efficacy of the combination therapies. We found that the combination of teriflunomide (64 µg/mL) and fluconazole (0.5-1 µg/mL) has a significant synergistic effect in all resistant Candida albicans isolates (n=4). Also, this drug combination could inhibit the immature biofilm biomass and hyphae formation of resistant Candida albicans. Galleria mellonella was used for testing the in vivo efficacy of this combination therapies. As for the Galleria mellonella larvae infected by resistant Candida albicans, teriflunomide (1.6 µg/larvae) combined with fluconazole (1.6 µg/larvae) significantly increased their survival rates, and reduced the fungal burden, as well as damage of tissue in comparison to that in the control group or drug monotherapy group. These results expand our knowledge about the antifungal potential of teriflunomide as an adjuvant of existing antifungal drugs, and also open new perspectives in the treatment of resistant Candida albicans based on repurposing clinically available nonantifungal drugs.

Electrochemical activation of peroxydisulfate by Ti/IrTaO2 anode for quick degradation of xanthate

High concentrations of residual xanthate in mineral processing wastewater often limit the reuse of tailing water. Targeted removal of xanthate is an effective strategy for improving the tailing water recycling rate. In this study, the degradation efficiency and mechanism of sodium ethyl xanthate (SEX) in an electroactivated peroxydisulfate (EAPDS) system were investigated systematically. To avoid the influence of co-existing organic and inorganic matters in real flotation wastewater, we used simulated SEX wastewater to conduct the efficiency and mechanism investigation. A significant synergistic effect between electrocatalysis and peroxydisulfate was observed during the SEX decomposition. When the initial concentration of SEX was 200 mg/L, it achieved 100% removal rate only in 30 min with PDS dosage of 5 mM at current density of 10 mA/cm2. The introduction of peroxydisulfate boosted the removal efficiency six-fold compared to electrocatalysis alone. UV-Vis spectroscopy and GC-MS analyses revealed that the intermediate products of SEX were C2H5OH and CS2. The reactive oxygen species induced in the EAPDS were identified using a series of detection methods. •OH, 1O2, h+, O2•− and electron transportation process (ETP) all contributed to SEX removal. The degradation mechanism in the EAPDS system was proposed based on the analysis of the reactive oxygen species and products. Application to real flotation wastewater was attempted as well. The effects of different operating conditions were also evaluated, including pH, coexisting anions, PDS dosage, and current density. This study provides a new approach for the rapid removal of residual xanthates from mineral processing wastewater.

Synergistic effect between two quaternary ammonium salts and thiourea as corrosion inhibitors for X70 steels in CO2 saturated 3.5% NaCl solution

Pyridine and quinoline quaternary ammonium salts (1-CPN and 1-CQN) were synthesized. The synergistic effects with different molar ratios of TU were investigated using weight loss, electrochemical measurements, surface characterization and theoretical calculations. The results showed that 1-CPN and 1-CQN had significant synergistic corrosion inhibition effects when combined with TU. The best synergistic effect occurred at 1-CPN/1-CQN:TU = 3:1, which had been proved by weight loss, electrochemical measurements and theoretical calculations. The mixture of 1-CPN/1-CQN with TU produced a denser adsorption film on the X70 steels surface, effectively inhibiting the corrosion process. Additionally, an intermolecular synergistic mechanism was proposed.

Synergistic effects of EDTA and lysozyme on the properties of hydroxypropyl starch nano antibacterial films

Hydroxypropyl starch (HPS) nano antibacterial films incorporating Ethylene Diamine Tetraacetic Acid (EDTA) and lysozyme (LY) were fabricated via solvent casting method. The synergistic effects of EDTA and LY on the microstructure, component interactions, color, optical, mechanical, barrier and antibacterial properties of HPS nano antibacterial films were evaluated. The results indicated that EDTA and LY were well dispersed in the matrix of the HPS nano antibacterial films, the film-forming substrates have good compatibility, resulting in a dense multi-layer structure of the HPS nano antibacterial films. The addition of EDTA and LY increased the color parameters (L*, a*, b* and △E*) of the HPS nano antibacterial films. The synergistic effects of EDTA and LY significantly decreased the light transmission of the HPS nano antibacterial films. The presence of EDTA and LY increased the tensile strength (TS) and the elongation at break (EAB) of the HPS nano antibacterial films. The TS and EAB of E2.5L1 reached the highest values of 6.329 MPa and 50.24 %, respectively. The incorporation of EDTA and LY had positive effects on the improvement of water vapor permeability (WVP) and oxygen permeability (OP). The WVP and OP of E2.5L1 reached the highest values of 0.9350 × 10−12 g cm/cm2•s•Pa and 0.297 × 10 −2 g m/m2 •d, respectively. In addition, EDTA and LY had significant synergistic effects on the antibacterial activity against S. aureus (Gram-positive bacteria) and E. coli (Gram-negative bacteria). E2.5L1 exhibited the highest antibacterial activity and the inhibition zone diameters of S. aureus and E. coli were 3.69 mm and 4.28 mm, respectively. The HPS nano antibacterial films incorporating EDTA and LY are potential functional packaging materials.

Oxidative Stress Participates in Age-Related Cataract Formation by Disrupting Connection between Lens Epithelial Cells through c-Src/VEGF Pathway

Purpose To observe the effects of oxidative stress on vascular endothelial growth factor (VEGF) and connections of lens epithelial cells. Methods Human lens epithelium of patients with age-related cataract (ARC), both SRA01/04 cells and whole mice lens stimulated by H2O2 were employed. VEGF in human aqueous humor of ARC-patients and the supernatant of SRA01/04 cells was determined by ELISA. The expressions of VEFG in human lens epithelium were detected by immunofluorescence staining. Multiple linear regression analysis and spearman rank-order correlation were used to determine the associations between VEGF and parameters of ARC individuals. In H2O2-induced SRA01/04 cells, Catalase (CAT), PP1 (inhibitor of c-Src kinase) and Avastin (VEGF antibody) were used to inhibit the effects of H2O2, activation of c-Src kinase and VEGF, which were detected by Western blot. The alterations of ZO-1 and N-cadherin were tested by immunofluorescence staining and Western blot. In H2O2-induced whole lens, the changes of opacification area in different treatment of inhibitors were observed. Results The secretion of VEGF in aqueous humor and expression of VEGF in the lens epithelium of ARC patients increased significantly with age. In H2O2-induced SRA01/04 cells, the VEGF in the supernatant was increased with the culture duration and the dose of H2O2. The expressions of p-Src418 and VEGF were also up-regulated, whereas the expressions of ZO-1 and N-cadherin were down-regulated. CAT effectively prevented these changes induced by H2O2, while PP1 inhibited not only p-Src418 but also up-regulation of VEGF, Avastin partially inhibited VEGF up-regulation. Both PP1 and Avastin prevented down-regulation of ZO-1 and N-cadherin, respectively, but Avastin combined with PP1 had no significant synergistic effects. In H2O2-induced cataract, CAT prevented development of opacification area effectively, and PP1 and Avastin did partially. Conclusions Oxidative stress disrupts connections of lens epithelial cells by activating c-Src/VEGF, inhibiting which may prevent cataract.

Hydrangea-like AuPtRu/ZnO-rGO Nanocomposites with Enhanced Peroxidase Mimiking Activity for Senitive Colorimetric Determination of H2O2.

In this study, a facile and cost-effective hydrothermal synthesis method was used to synthesize zinc oxide nanoflowers modified by reduced graphene oxide, and subsequently, trimetallic AuPtRu nanoparticles(AuPtRuNPs) were supported via the reduction method for high-sensitivity colorimetric detection of H2O2 in weakly acidic solutions. Compared to monometallic and bimetallic nanoparticles, trimetallic nanoparticles exhibit significant synergistic effects and enhanced catalytic activity. After providing a three-dimensional structure with multiple pores by zinc oxide and enhancing electron transfer ability by reduced graphene, the trimetallic nanocomposites (AuPtRu/ZnO-rGO) exhibited excellent peroxidase-mimicking activity, which can effectively catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue oxidation product (oxTMB) in the presence of H2O2. Compared to horseradish peroxidase (HRP), AuPtRu/ZnO-rGO demonstrated significantly enhanced catalytic velocity (Vmax = 6.16 × 10-8 M/s) and affinity (Km = 0.02) for H2O2. The study of the catalytic mechanism showed that trimetallic Au, Pt, and Ru could effectively catalyze H2O2 to produce hydroxyl radicals (•OH) to accelerate the oxidation of TMB and enhance the peroxidase-mimicking activity of the AuPtRu/ZnO-rGO nanocomposites. The results showed that the as-synthesized hydrangea-like AuPtRu/ZnO-rGO nanocomposites showed enhanced peroxidase-mimicking activity. It could be used for the colorimetric detection of H2O2 in the range 5-1000 μM with a LOD of 3.0 μM (S/N = 3), and the recoveries are 93.0-101.7%. In addition, the AuPtRu/ZnO-rGO nanocomposites have good applicability for sensitive colorimetric determination of H2O2 in milk, and it has broad application prospects as a multifunctional sensing platform in the food processing industry.

Correlation Analysis of Key Residue Sites between Computational-Aided Design Thermostability d-Amino Acid Oxidase and Ancestral Enzymes.

The d-amino acid oxidase (DAAO) from Rhodotorula taiwanensis has proven to have great potential for applications due to its excellent catalytic kinetic parameters. However, its poor thermal stability has limited its performance in biocatalysis. Herein, starting from the variant SHVG of RtwDAAO, this study employed a comprehensive computational design approach for protein stability engineering, resulting in positive substitutions at specific sites (A43S, T45M, C234L, E195Y). The generated variant combination, SHVG/SMLY, exhibited a significant synergistic effect, leading to an extension of the half-life and Tmapp. The ancestral sequence reconstruction revealed the conservation of the variant sites. The association of the variant sites with the highly stable ancestral enzyme was further explored. After determining the contribution of the variant sites to thermal stability, it was applied to other homologous sequences and validated. Molecular dynamics simulations indicated that the increased hydrophobicity of the variant SHVG/SMLY was a key factor for the increased stability, with strengthened intersubunit interactions playing an important role. In addition, the physical properties of the amino acids themselves were identified as crucial factors for thermal stability generality in homologous enzymes, which is important for the rapid acquisition of a series of stable enzymes.

Numerical analysis on the direction to improve thermal conductivity of polymer composites filled with spherical particles

The research on thermal conductivity of insulating polymer-matrix composites filled with spherical particles (PMCs-SP) is far below the requirements for industrial utility. To find the improving direction for the thermal conductivity of PMCs-SP (KPMCs-SP), a series of PMCs-SP models filled with randomly distributed spherical particles were established. The PMCs-SP models were validated by comparing the calculated KPMCs-SP with the experimental data. It is found that KPMCs-SP increases with the increasing volume fraction of spherical particles, and the influence of filler size and interfacial thermal resistance on KPMCs-SP shows a significant synergistic effect. The formation of heat conduction chains could effectively improve KPMCs-SP. Increasing the number of heat conduction chains and decreasing the spacing of spherical particles can both increase the KPMCs-SP. To quantify the effect of heat conduction chains on KPMCs-SP, the concept of compactness of heat flow chains (C) was creatively proposed. The KPMCs-SP-C curve presences a threshold value, C0 = 0.6372, beyond which KPMCs-SP could be significantly enhanced. In addition, the theoretical specific thermal resistance of PMCs-SP (Rλ,PMCs-SP) was first calculated. For PMCs-SP with the default parameters, the theoretical minimum Rλ,PMCs-SP converged to ∼ 0.72 m·K·W−1.

Effects of straw addition on biological nitrogen fixation under continuous and intermittent flooding irrigation in a rice cropping system

Both straw addition and water management affect biological nitrogen fixation (BNF), but it is still unclear how straw addition impacts BNF under continuous or intermittent flooding irrigation in a rice cropping system. A 15N2-labelling chamber system placed in a rice field was used to evaluate BNF under straw addition with continuous or intermittent flooding irrigation for 90 days. The nitrogenase reductase (nifH) gene and reverse transcription gene (cDNA) in the soil were amplified using Real-time polymerase chain reaction (qPCR), and nifH gene high-throughput sequencing was applied. The BNF in the straw addition treatment (14.0 g straw added to 1.40 kg soil) under continuous flooding (14.3 kg ha-1) was 116% higher than that under intermittent flooding (6.62 kg ha-1). Straw addition and continuous flooding showed significant synergistic effects on BNF and the gene copy numbers of nifH DNA and nifH cDNA. The increase in BNF was mainly due to the increase in the abundance of heterotrophic diazotrophs such as Desulfovibrio, Azonexus, and Azotobacter. These results indicate that straw addition under continuous flooding stimulates BNF relative to intermittent flooding, which may ultimately lead to a rapid enhancement of soil fertility.

Impact of Nitrogen on Growth and Yield of Broccoli (Brassica oleracea L. var. italica) under Open and Protected Environment

A field experiment was conducted at Vegetable Research Farm, Department of Agriculture, Khalsa College, Amritsar during the year 2020-21. Ten treatments with three replications were designed in a Factorial Randomized Block Design to conduct the research. The obtained results showed the significant synergistic effect of environmental conditions and nitrogen doses on the growth, yield and quality of broccoli as compared to the control. Better vegetative and yield characters were observed in the protected environment with a 125% nitrogen application, while the utmost quality was observed under the protected environment with a 100% nitrogen application, and control recorded the poorest result of all.

Investigation of the inhibitory combined effect and mechanism of (−)-epigallocatechin gallate and chlorogenic acid on amylase: Evidence of synergistic interaction

Both (−) -epigallocatechin gallate (EGCG) and chlorogenic acid (CHA) have shown inhibitory effects on α-amylase. However, there may be synergistic or antagonistic effects among them. This study utilized the ZIP model to examine the inhibitory impact of EGCG and CHA on amylase and analyze the mechanism of inhibition. The results showed that EGCG and CHA had a significant synergistic effect when the EGCG was between 0.25 and 0.5 mg/mL and the CHA was 2–4 mg/mL. The optimal synergistic ratio was EGCG:CHA = 1:8. The inhibitory kinetics indicate that EGCG, CHA, and the complex exhibit competitive inhibition, mixed inhibition, and mixed inhibition towards α-amylase, respectively. Fluorescence spectroscopy revealed that the combined use of EGCG and CHA exhibited a more significant quenching effect. The findings from synchronous fluorescence and molecular docking analyses further demonstrated that EGCG and CHA exhibited interactions with distinct amino acids and occupied separate binding sites simultaneously. This study aims to provide valuable insights into the blending of tea and coffee, with the hope of generating new ideas for the development of hypoglycemic food products.

A boost lubrication performance of reduced graphene oxide synergizing with carbonized polymer dots via tribochemistry

Reduced graphene oxide (rGO) can become a new generation of lubricating materials because of its unique physicochemical properties. However, the aggregation phenomenon of rGO in base oils remains a significant bottleneck for its sustainable and industrial applications. To address this issue, we developed a strategy to enhance the lubricating properties of rGO using carbonized polymer dots (CPDs) assisted by the dispersant Span 80 (SP). This study demonstrated the effectiveness of this approach using various analytical techniques. Experimental data showed that the prepared CPD/rGO/SP nanofluid exhibited significant dispersion stability in sedimentation tests. From a macroscopic tribological viewpoint, the CPD/rGO/SP nanofluid exhibited excellent friction reduction and antiwear properties. Compared with the base oil, its average friction coefficient and wear scar diameter were reduced by 33.1 % and 39.8 %, respectively. Further experiments also revealed that the nanofluid exhibited efficient lubrication characteristics under certain loads, certain rotational speeds, and prolonged lubrication conditions. Mechanism analysis indicated that the interfacial interaction between CPDs and rGO produced a significant synergistic effect, which provided the conditions for the formation of a continuous and dense tribofilm, effectively isolating frictional mating surfaces, and achieving efficient lubrication. Therefore, this study presents a simple and universal solution to address the key issue of rGO in oil-based lubrication, laying the foundation for its large-scale industrial production.

NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment.

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the piggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45.1% (±26.1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and γ-secretase inhibitors (GSIs), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrates the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

Combinatorial Optimization of Chemotherapeutic Agents on T-Cell Acute Lymphoblastic Leukemia

Introduction: Up to now, treatment options for T-cell acute lymphoblastic leukemia (T-ALL) remain quite limited. This study aims to assess the efficacy of monotherapies and combination of chemotherapeutic agents for T-ALL. Jurkat, CCRF-CEM are late T-cell progenitor (LTP) cell lines, while Loucy is early T-cell progenitor (ETP) cell line characterized by an immature phenotype. The drugs under evaluation include venetoclax, a selective BCL-2 inhibitor; cytarabine, a cytosine analog with established antineoplastic activity; bendamustine, an alkylating agent; and azacitidine, a DNA methyltransferase inhibitor. Given the notable tumor heterogeneity observed in T-ALL, the comprehensive assessment of these therapeutic agents on Jurkat, CCRF-CEM, and Loucy may render valuable insights for treatment strategies in T-ALL. Methods: Cell lines were cultured in RPMI-1640 medium supplemented with 10% FBS and 1% penicillin-streptomycin at 37°C with 5% CO2. Venetoclax, bendamustine, and azacitidine were prepared as stock solutions in DMSO, while cytarabine was prepared in distilled water. Monotherapies (venetoclax, cytarabine, bendamustine and azacitidine) and combination therapies (venetoclax plus cytarabine, venetoclax plus bendamustine and venetoclax plus azacitidine) were administered. A control group received DMSO or distilled water only. Cell viability was assessed after 48 hours by using Trypan blue and colorimetric method (MTS assay) on cells treated with various drug concentrations. Statistical analysis was conducted using the SynergyFinder Plus and drc R package, with significance set at p < 0.05. Results: Our study demonstrated that T-ALL cell lines displayed a different pattern of drug sensitivities according to combination of chemotherapeutic agents. Loucy showed greater sensitivity to venetoclax while Jurkat and CCRF-CEM exhibited higher sensitivity to cytarabine, bendamustine, and azacitidine. When conducting drug combinations on Jurkat and CCRF-CEM, the addition of venetoclax to cytarabine, bendamustine, or azacitidine resulted in an additive effect, with Loewe synergic scores ranging from -10 to 10 for each combination. On the other hand, Loucy demonstrated a distinct pattern of response; the combination of venetoclax with cytarabine showed additivity (Loewe synergic score: 8.45 and 5.82 with MTS and trypan blue assays, respectively), while venetoclax combined with bendamustine or azacitidine showed a synergistic effect (Loewe synergic score > 10 with MTS assay). Notably, among these combination treatments on Loucy, the pairing of venetoclax with bendamustine showed the most significant synergistic effects, with a Loewe score of 16.6. Conclusion: Venetoclax-based chemotherapeutic combinations exhibited various responses in T-ALL cell lines. Of note, the combination of venetoclax plus bendamustine showed potent synergistic effects in all T-ALL cell lines. These findings warrant further study to develop fundamentally curative therapeutic strategies in T-ALL.

Lipid-Mediated Modulation of DNA Damage Signaling As a Prognostic and Therapeutic Strategy Against Multiple Myeloma

Multiple myeloma (MM), characterized by the accumulation of tumor plasma cells in the bone marrow, is the second most common hematologic cancer. Occurrence of chemoresistance invariably leads patients to relapse and results in loss of clinical control over the disease. Cancer cells show a deregulation of different pathways, including lipid metabolism alterations and high genomic instability. Yet, no functional relationship between these two features has been identified. We have shown in a previous work that the metabolism of lipids impacts in how DNA damage is detected, signaled and repaired (Ovejero et al 2023 EMBO J). We reported that breaks in the DNA trigger the birth of lipid droplets (LD), a central lipid-storage organelle, and that this event is key for cells to tolerate this specific DNA damage. Given that MM cells are particularly dependent on DNA repair pathways for survival, we postulated that new therapeutic perspectives would emerge by targeting the formation of LD. Analysis of the LD formation gene expression profile of a cohort of newly diagnosed MM patients (UAMS-TT2 MM cohort, n = 345) allowed the establishment of a LD score comprising 13 genes associated with a significant prognostic value after multiple testing correction. The LD score gene expression-based risk score enabled the identification of MM patients with a poor outcome. The prognostic value of the LD score was validated in two other independent cohorts of newly diagnosed patients (HM cohort, n = 206; UAMS-TT3 MM cohort, n = 158) and in a cohort of patients at relapse treated with anti-CD38 MoAb (Mtp-Dara, n = 49). We subsequently studied the presence of LD in primary MM cells obtained from 34 patients. Importantly, we observed a significant positive correlation between the percentage of LD-positive cells and the value of the LD score (p = 0,02). This prompted us to investigate the therapeutic interest of interfering with LD formation to target MM cells. To this end, we treated 26 Human Myeloma Cell Lines (HMCLs) with drugs selected on an educated-guess basis and identified positive hits. These results were validated employing a shRNA strategy in selected HCMLs. Flow cytometry analyses revealed that this regime triggered a cell cycle halt, where cells accumulated in the G 1 phase at the expense of S and G 2. This was accompanied by a decrease in c-MYC expression, as well as an induction of cell proliferation arrest markers such as the G 1-checkpoint CDK inhibitors p21 and p27. Mechanistically, we observed a significant increase in Chk1 and Chk2 phosphorylations, two downstream events of DNA damage signaling despite that basal DNA damage levels remained unchanged. Together, these data convey the notion that limiting LD formation in MM cell lines boosts the detection of endogenously present DNA damage, thus enforcing a more robust DNA damage signaling which culminates in a drastic loss of proliferative capacity and viability. Of major importance, we validated the therapeutic interest of this strategy in primary MM cells from patients (n = 19). A significant higher toxicity in MM cells was found compared to normal cells from the microenvironment (tumoral: ****, p < 0.0001; normal: ***, p = 0,0006). Moreover, we tested the therapeutic interest of combining this approach with conventional treatments used in MM. Interestingly, we identified a synergistic effect when combined with melphalan, a DNA-alkylating agent used in MM treatment. This synergy was observed in HCMLs and in primary MM cells of patients (n = 7). Furthermore, significant synergistic effects were found in HMCLs by combining with the proteasome inhibitors bortezomib and carfilzomib. Altogether, these data unveil both the LD score and LD-bearing cell quantification as new prognostic factors in MM, and open new therapeutic perspectives to improve the treatment of MM patients by targeting LD metabolism.

Revealing the synergy mechanisms of organic components anaerobic co-digestion from the prevailing tendency of endogenous inhibitors

The anaerobic co-digestion (AcoD) test among three organic components (model compounds) under high feeding load was carried out in this study, then the dynamic change of intermediate metabolic inhibitors was detected and analyzed to identify the interaction mechanism among organic components from the prevailing tendency of endogenous inhibitors. Carbohydrate and protein show significant two-way synergistic effects for methane production. The addition of protein can supplement additional alkalinity to alleviate the sharp drop of pH (from 4.56 to 6.73) and avoid the acidification caused by high concentration of carbohydrate. Additionally, volatile fatty acids (VFAs) produced by carbohydrate can transform free ammonia to ammonium ion with the largest drop of 54%, thus reducing ammonia toxicity. Carbohydrate and lipid show one-way synergistic effects, namely, lipid can reduce VFAs accumulation by 49% through long chain fatty acids (LCFAs) inhibiting action, and then avoid complete rancidity of carbohydrate fermentation at high concentration. However, protein and lipid show serious two-way antagonistic effects, especially under high load digestion. On one hand, LCFAs would weaken ammonia volatilization and thus aggravate ammonia inhibition; On the other hand, protein would not only accelerate the formation of LCFAs inhibition by promoting lipid hydrolysis, but also transform the degradation pathway of oleic acid (unsaturated LCFAs) and then increase the proportion of stearic acid from 5.17% to 40.33%, which is of higher toxicity than palmitic acid.

Hierarchical 3D porous trimetallic palladium-iron and cobalt on nickel foam as electrocatalyst for large current density oxygen evolution reaction in alkaline seawater

Electrolysis in seawater is a low-cost but difficult method of producing hydrogen. Herein, self-assembled hierarchical three-dimensional (3D) porous trimetallic palladium-iron and cobalt oxide anchored on a cheap and high surface area nickel foam (NF) (PdFeCo3−xO4/NF) were synthesized using a simple and low-cost impregnation-hydrothermal and thermal reduction strategy. The as-fabricated PdFeCo3−xO4/NF electrode showed both superhydrophilic and superaerophobic properties, which favored the fat removal of oxygen bubbles from the electrode surface owing to the close interaction between the electrode and electrolyte. Furthermore, the significant synergistic effect of trimetallics and the NF-matrix resulted in substantially enhanced oxygen evolution reaction (OER) intrinsic activity. The self-assembled PdFeCo3−xO4/NF catalyst exhibited critical low overpotentials of 300 and 340 mV to achieve an extremely large current density of 100 mA cm−2 in 1 M KOH solution and 1 M KOH seawater. Cell voltages as low as 1.44 and 1.51 V were required to drive 10 mA cm−2 in alkaline solution and seawater electrolytes for the full cell overall water splitting performance. This work suggests a promising strategy for developing next-generation electrocatalysts appropriate for natural seawater with cost-effective.

Toxicity of binary-metal mixtures (As, Cd, Cu, Fe, Hg, Pb and Zn) in the euryhaline rotifer Proales similis: Antagonistic and synergistic effects

Data regarding the effects of binary metal mixtures in marine zooplankton are scarce, particularly for rotifers. We examined the toxicity of 21 binary equitoxic mixtures of As, Cd, Cu, Fe, Hg, Pb, and Zn on the euryhaline rotifer Proales similis. The toxic units (TU50) revealed that 20 of these binary mixtures exhibited synergistic effects (TU50 < 1.00). The AsHg mixture showed a strong antagonistic effect (TU50 = 2.39), whereas the HgCu interaction exhibited a significant synergistic effect (TU50 = 0.29) on P. similis. TU50 values were <0.60 in all cases that showed synergism (80 %). Regarding the MIXTOX analysis, 13 binary mixtures presented some level of synergism, while two mixtures presented only additivity. Results emphasize the need for environmental agencies to revise and readjust protection guidelines for marine biota in response to the evident synergistic effects occurring at metal mixtures concentrations below the current permissible limits.

Enhancing mechanical properties and thermal conductivity in polymer bonded explosives by multi-scale surface modification of carbon fibers

Poor interfacial interaction and strength largely restrict the overall performance and practical application of carbon fibers (CFs) reinforced composites. The favorable interfacial properties were the key to realize superior mechanical properties in composites. Herein, we reported a novel multi-scale surface modification strategy of CFs to strengthen interfacial properties. Based on chemical oxidation treatment, the surface of CFs was further in situ grafted by a crosslinked high-strength polymer network consisting of aromatic diisocyanate, graphene oxide (GO) and polyethylenen glycol (PEG), which significantly improved the interfacial bonding and mechanical strength of interface layer itself. Benefitting from this multi-scale surface treatment, a high-efficiency mechanical enhancement of polymer bonded explosives (PBX) was achieved. With only 0.3 wt% fiber content, the maximum tensile and compressive strength PBX composites were both significantly improved, which were 63 % and 39 % higher than those of pure PBX, respectively. Meanwhile, the thermal conductivity was also enhanced, yielding a significant synergistic enhancement effect. The interface failure mechanism of the composite under stress was clarified by the fracture morphology characterization. This study sheds a light for exploring novel surface modification and has the potential application in in high performance polymer composites.

How do energy-saving policies improve environmental quality: Evidence from China’s Top 10,000 energy-consuming enterprises program

Treating China’s Top 10,000 Energy-Consuming Enterprises Program (T10000P) as a quasi-natural experiment, this is the first study to investigate the synergistic effects of the representative energy-saving policy on environmental quality at the micro-level. We create a panel data set by matching China’s Environmental Statistics Database, Industrial Enterprise Database, and State Intellectual Property Office Database, and employ the difference-in-differences model to identify the policy’s environmental effects and their mechanisms. The results show that the T10000P can effectively lower chemical oxygen demand (COD) and sulfur dioxide (SO2) emissions, which still hold after a series of robustness checks, indicating that the policy has a significant synergistic effect on environmental quality improvement. Furthermore, compared with small polluters, the T10000P has a higher pollutant emission inhibition effect on large polluters. Such a positive environmental impact is confirmed for energy-intensive, large, rather than non-energy-intensive and small enterprises, showing heterogeneous effects across different enterprises. We also find that promoting green technology innovation and environmental compliance are the important channels through which the policy improves environmental quality. Therefore, the energy-saving policy can improve environmental quality by setting constrained targets on energy consumption, especially in developing countries.