Strong Synergistic Interaction Research Articles

Pd nanoparticles on DUT-67-PZDC-derived N-doped carbon for efficient H2 generation from formic acid dehydrogenation

It is important to develop heterogeneous catalysts with high efficiency and stability to catalyze formic acid (FA, HCOOH) dehydrogenation. Herein, through pyrolysis of DUT-67-PZDC and etching in a hydrofluoric acid (HF) solution, the HF-etched N-doped carbon (HNDC) carrier was obtained. Palladium nanoparticles (Pd NPs), with an average particle size of 3.0 nm, were prepared on the HNDC support using a simple chemical co-reduction method. The optimized Pd/HNDC catalyst demonstrates excellent catalytic activity, the initial turnover frequency (TOF) value is 6001 h−1 at 50 °C with the incorporation of sodium formate (SF) as an additive, and the FA conversion and hydrogen (H2) selectivity could be up to 100%, which is comparable to the majority of MOF-derived heterogeneous catalysts published to date. Additionally, the Pd/HNDC can maintain good stability in five consecutive FA dehydrogenation runs with only a slight decrease. Such remarkable catalytic performance of Pd/HNDC is mainly ascribed to the unique structure of HNDC support with high surface area and hierarchical pore characteristic, the strong synergistic interaction between Pd NPs and the N sites on HNDC, as well as the ultrasmall size and high dispersion of Pd NPs as the catalytic active site. This work offers an efficient method for assembling highly active catalysts for FA dehydrogenation.

Synergistic interaction between a toxicant and food stress is further exacerbated by temperature

Global biodiversity is declining at an unprecedented rate in response to multiple environmental stressors. Effective biodiversity management requires deeper understanding of the relevant mechanisms behind such ecological impacts. A key challenge is understanding synergistic interactions between multiple stressors and predicting their combined effects. Here we used Daphnia magna to investigate the interaction between a pyrethroid insecticide esfenvalerate and two non-chemical environmental stressors: elevated temperature and food limitation. We hypothesized that the stressors with different modes of action can act synergistically. Our findings showed additive effects of food limitation and elevated temperature (25°C, null model effect addition (EA)) with model deviation ratio (MDR) ranging from 0.7 to 0.9. In contrast, we observed strong synergistic interactions between esfenvalerate and food limitation at 20°C, considerably further amplified at 25°C. Additionally, for all stress combinations, the synergism intensified over time indicating the latent effects of the pesticide. Consequently, multiple stress substantially reduced the lethal concentration of esfenvalerate by a factor of 19 for the LC50 (0.45 to 0.024 μg/L) and 130 for the LC10 (0.096 to 0.00074 μg/L). The stress addition model (SAM) predicted increasing synergistic interactions among stressors with increasing total stress.

Exploring the Relationship Between Education, Living Environment, and Anxiety/Depression Among Stable Patients: Insights from the COPD-AD China Registry Study.

Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain. The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI). Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06-2.29 and OR:2.15, 95% CI 1.51-2.05) or depression (OR:1.62, 95% CI 1.17-2.27 and OR: 2.01, 95% CI 1.46-2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83-16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77-24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41-95.27; RERI: 6.31, 95% CI 1.60-11.01; AP: 0.8, 95% CI 0.66-0.94) and depression (SI: 31.31, 95% CI 1.59-617.04; RERI: 10.44, 95% CI 2.66-18.23; AP: 0.89, 95% CI 0.8-0.97). Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.

Design, sonic solvothermal synthesis, synergistically improved bioactivity and photo-self-degradability of sulfonyl phenylpyrazole two-site alkaloids fused amides and amine units as GABA receptor inhibitors

Amide alkaloids and amine alkaloids play an important role in insecticidal and antibacterial activity, respectively. What activity is produced when they fuse with phenylpyrazole parent structure to form a two-site alkaloid? A series of sulfonyl phenylpyrazole alkaloids (PAs) incorporating amides and amine two-site moiety were diversified designed and one-pot sonic solvothermal synthesized for the first time, which were fully characterized and crystal analysis. Preliminary bioassays indicated that PA5b had excellent insecticidal bioactivity against 3rd instar larvae of P. xylostella and M. separata and 4.1 times more bacteriostatic activity against A. tumefaciens than parent compound. The results of molecular docking revealed that amides and amine units in PAs had strong synergistic interactions with GABA receptors, such as hydrogen, halogen and hydrophobic bonds, resulting in high insecticidal activity and strong bacteriostatic effects through two-site combination. Furthermore, PA5b formed π-cation interactions with the GABA receptor, verified by crystal structure and Hirshfeld surface analysis. Photophysical tests exhibited that amide and amine moiety of PAs expanded the conjugation system to improve their light absorption and fluorescence, and PAs possessed photo-self-degradability under simulated natural light irradiation, which could be reconverted to phenylpyrazole parental fragments, thus improving their bioactivity and reducing residues. The structure-properties relationship of sulfonyl phenylpyrazole two-site alkaloids was analyzed by CoMFA modeling and Hirshfeld surface for the presence of bioactive sites at the sulfone and amine sites. These findings lay the foundation for the development of two-site alkaloid insecticides and provide new ideas for their natural degradation and fluorescent detection.

Susceptibility of Staphylococcus aureus to Anti-Inflammatory Drugs with a Focus on the Combinatory Effect of Celecoxib with Oxacillin In Vitro.

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases due to antibiotic resistance. This has encouraged the development of innovative strategies, such as combination therapy, to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory drugs and the combined antimicrobial effect of celecoxib and oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs against standard strains and clinical isolates of S. aureus, including methicillin-resistant strains (MRSAs), were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated using checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all tested strains (MICs ranging from 32 to 64 mg/L), followed by that of diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/L). Several synergistic effects were observed against the tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/L, with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/L). This is the first report on the combined antistaphylococcal effect of celecoxib and oxacillin. These findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. This study further indicates that celecoxib could resensitize certain MRSA strains, in some cases, to be susceptible to β-lactams (e.g., oxacillin) that were not previously tested. It is essential to mention that the in vitro concentrations of anti-inflammatory drugs are higher than those typically obtained in patients. Therefore, an alternative option for its administration could be the use of a drug delivery system for the controlled slow release from an implant at the infection site.

Catalytic Water Electrolysis by Co-Cu-W Mixed Metal Oxides: Insights from X-ray Absorption Spectroelectrochemistry.

Mixed metal oxides (MMOs) are a promising class of electrocatalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Despite their importance for sustainable energy schemes, our understanding of relevant reaction pathways, catalytically active sites, and synergistic effects is rather limited. Here, we applied synchrotron-based X-ray absorption spectroscopy (XAS) to explore the evolution of the amorphous Co-Cu-W MMO electrocatalyst, shown previously to be an efficient bifunctional OER and HER catalyst for water splitting. Ex situ XAS measurements provided structural environments and the oxidation state of the metals involved, revealing Co2+ (octahedral), Cu+/2+ (tetrahedral/square-planar), and W6+ (octahedral) centers. Operando XAS investigations, including X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS), elucidated the dynamic structural transformations of Co, Cu, and W metal centers during the OER and HER. The experimental results indicate that Co3+ and Cu0 are the active catalytic sites involved in the OER and HER, respectively, while Cu2+ and W6+ play crucial roles as structure stabilizers, suggesting strong synergistic interactions within the Co-Cu-W MMO system. These results, combined with the Tafel slope analysis, revealed that the bottleneck intermediate during the OER is Co3+ hydroperoxide, whose formation is accompanied by changes in the Cu-O bond lengths, pointing to a possible synergistic effect between Co and Cu ions. Our study reveals important structural effects taking place during MMO-driven OER/HER electrocatalysis and provides essential experimental insights into the complex catalytic mechanism of emerging noble-metal-free MMO electrocatalysts for full water splitting.

Binary wax oleogels: Improving physical properties and oxidation stability through substitution of carnauba wax with beeswax.

High concentrations of carnauba waxes (CRWs) that can compromise organoleptic properties are required to create self-sustained and functional oleogels. The weak physical properties and stability of 4% w/w CRW-rice bran oil (RBO) oleogel were addressed by substituting CRW with beeswax (BW) in different weight ratios. The texture profile analyzer revealed that substituting only 10% (weight ratio) of CRW with BW improved the hardness compared to the mono-CRW oleogel. The hardness of binary oleogels increased gradually as the proportion of BW increased. At a BW ratio of 70% or more, the hardness was three times higher than that of mono-BW oleogel. Rheology analysis showed the same trend as the large deformation test; however, the hardest binary oleogels had lower critical strain and yield point compared to the mono-wax oleogels, implying that they are more prone to lose their structure upon applied stress. Nevertheless, nearly all binary mixtures (except for 10%BW90%CRW) showed oil-binding capacities above 99%, suggesting improved nucleation and crystallization process. Polarized light microscopy showed the coexistence of BW and CRW crystals and changes in the size and arrangement of wax crystals upon proportional changes of the two waxes. X-ray diffraction confirmed no differences in the peaks' location, and all oleogels had β' polymorphism. Differential scanning calorimetry showed eutectic melting behavior in some binary blends. Oxidation stability in the binary wax oleogels improved as compared to the mono-wax oleogel and bulk RBO. BW and CRW mixtures have promising oil-structuring abilities and have various properties at different ratios that have the potential to be used as solid fat substitutes. PRACTICAL APPLICATION: As a trending green oil-structuring technology, oleogelation has shown great potential to reduce saturated fats in food systems. The current research provides valuable fundamental information on the strong synergistic interactions between beeswax and carnauba wax that have the potential to be used as solid fat substitutes created with a much lower total concentration of the required wax. This will help create wax oleogels with better organoleptic properties and less negative waxy mouthfeel. Such knowledge could prove beneficial for the development of healthy products that have potential applications in meat, bakery, dairy, pharmaceutical, as well as cosmetic industries.

Enhancing selective nitrate-to-ammonia electrocatalysis with high-performing Ni2P embedded nitrogen phosphide doped carbon (NPC) deposited on CP: Unprecedented performance and stability

One of the biggest challenges to the sustainable manufacture of liquid ammonia and the prevention of worldwide water contamination is the development of effective electrocatalysts for the electrochemical reduction of nitrate (NO3−) to NH3 with high stability. Herein, a highly active and serviceable electrocatalyst is synthesized by pyrolysis, composed of nanostructure nickel phosphide (Ni2P) embedded in nitrogen phosphide doped carbon (NPC) followed by deposition on carbon paper (CP) to improve the electrocatalytic nitrate reduction. Various characterization techniques investigate the crystallinity, morphology, and chemical components of the Ni2P-NPC/CP nanoparticles. The results support the formation of nanostructure Ni2P and strong synergistic interactions between Ni2P and NPC, which resulted in substantial active sites and high electrical conductivity. Excellent performance of Ni2P-NPC/CP nanoparticles is achieved for electrocatalytic NO3− reduction with an NH4+ yield rate of 2.468 mg h−1 mgcat.−1 and Faradaic efficiency (FE) of 84.6% at −1.2 V vs. RHE. Additionally, Ni2P-NPC/CP nanoparticles exhibit exceptional robustness and endurance. Studies using isotope labeling have been carried out, and the results show that nitrate reduction produces ammonia. Ni2P-based electrocatalysts can effectively treat nitrate wastewater to recover ammonia and facilitate its use in diverse industrial applications.

Notch corrosion fatigue behaviour and simplified strain energy density-based notch fatigue life assessment of Grade-A shipbuilding steel

Corrosion fatigue is a key challenge in lifecycle management of ship hull structures. Although sea wave fatigue stresses are linear-elastic, highly-damaging elastic–plastic conditions occur at geometrical discontinuities or notches. Estimation of notch stress-strains to characterize notch fatigue behaviour conventionally requires large computational efforts. Also, constant strain energy density (SED), as a driving force, is far more effective in realistic applications versus constant stress and strain fatigue life approaches. Identified research gaps were the development of a simplified SED approach for fatigue life assessment of hole-notched structures. Fatigue studies were conducted on hole-notched specimens of Grade-A shipbuilding steel in air and corrosion mediums. Strong synergistic interactions of corrosion and fatigue damage mechanisms were studied by scanning electron microscope (SEM) fractography. Notch corrosion fatigue life was reduced by 70% from notch air fatigue life due to environmental effect. Two new parameters are proposed to improve the efficiency of notch fatigue life assessment, namely “fatigue notch strain energy density concentration factor (K_SED) and “fatigue notch toughness”. This improved fatigue life assessment method was demonstrated as equally reliable but much simpler to implement, eliminating the complex computational analysis. This improved method has promising applications in real-time structural health monitoring (SHM) of ship hull structures.

MnS-BaS Heterostructures as Effective Catalysts for Oxygen Reduction Reaction.

The inadequate electrical conductivity of metal sulfides, along with their tendency to agglomerate, has hindered their use in energy storage and catalysis. The construction of a heterojunction can ameliorate these deficiencies to some extent. In this paper, MnS-BaS heterojunction catalysts were prepared by a hydrothermal method, which is a simple and inexpensive process. The MnS-BaS heterojunction catalysts exhibited superior performance owing to the strong synergistic interaction between MnS and BaS. Density functional theory (DFT) calculations reveal strong interactions at the heterojunction interface and significant electron transfer between MnS and BaS, which further modulates the electronic structure of Mn. The elevation of the center of the d-band enhances the adsorption of oxygen and oxygen-containing intermediates on the catalyst, thus promoting the oxygen reduction reaction (ORR). The practical application of MnS-BaS catalysts was tested by assembling zinc-air batteries. This study provides a rational strategy for designing transition metal catalysts that are efficient and low cost.

Abstract 1251: Tobacco smoke alters the adaptive landscape of lung adenocarcinoma and influences the strength of epistatic interactions

Abstract Tobacco smoke produces both mutagenic and physiological effects, altering the mutation rate of cells and the selection acting on them in the damaged lung environment, and facilitating its role in driving cancer progression. In addition to these gene-by-environment interactions, gene-by-gene epistatic interactions also shape the adaptive landscape, influencing the evolutionary trajectories of cancer. Understanding the influence of tobacco smoke on the epistatic trajectories of lung cancer progression would help guide the development of targeted therapies that are more effective for smoker or never-smoker populations. To address this need, we constructed a continuous-time Markov chain model for the evolutionary trajectories of lung adenocarcinoma (LUAD), the most common subtype of lung cancer and the most frequent subtype among never-smokers. Using thousands of tumor sample sequences aggregated across studies, we profiled the trajectories of LUAD in smokers and never-smokers and estimated the rates at which mutations are gained from each possible set of pre-existing mutations, or genetic states. We then accounted for differences in baseline mutation rates to quantify the selective benefit of mutations. We find that epistasis is prevalent in LUAD, with several strong synergistic interactions—such as between RB1 and EGFR mutations- and antagonistic interactions-such as between EGFR and KEAP1 or KRAS mutations. Additionally, we identify non-additive epistatic effects: STK11 mutations are synergistic with KEAP1 and KRAS mutations but do not experience additional selection when both are mutated. In contrast, GNAS mutations are not synergistic with KEAP1 or RBM10 mutations alone but are synergistic with their co-mutation. Smoking has a large influence on the adaptive landscape, with several common mutations being preferentially selected in never-smoker cancers, including EGFR, SMAD4, GNAS, and PIK3CA mutations. KEAP1, STK11, and KRAS mutations are preferentially selected in smoker cancers. Smoking’s physiological influence also affects the strength of certain epistatic interactions, such as between STK11 and KEAP1 mutations. Overall, we find that smoking not only increases the mutation rate of lung cells but also substantially alters the adaptive landscape of lung adenocarcinoma, leading to clinically relevant differences in selection on mutations between smoker and never-smoker cancers. We additionally detect frequent pairwise and higher-order epistatic effects in LUAD that may inform the personalized application of targeted therapies. Citation Format: Krishna Dasari, Jorge Alfaro-Murillo, Jeffrey Townsend. Tobacco smoke alters the adaptive landscape of lung adenocarcinoma and influences the strength of epistatic interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1251.

Hierarchical FeOxHy@Ni3B hybrid for efficient alkaline oxygen evolution at high current density

Electrocatalysts with high activity and long-term durability are vital toward large-scale hydrogen production from electrocatalytic water splitting. Here, the self-supported electrode (FeOxHy@Ni3B/NF) with hierarchical heterostructure was simply prepared by using Ni3B chunks grown on nickel foam as substrate to in situ form vertical FeOxHy nanosheets. Such hybrid shows efficient oxygen evolution reaction activity with overpotentials as low as 267 and 249 mV at 100 mA cm−2 in 1 M KOH solution and 30 wt% KOH solution, respectively. Meanwhile, it also exhibits excellent catalytic stability, sustaining catalysis at 500 mA cm−2 in 1 M KOH solution for 200 h, and even for 200 h at 1000 mA cm−2 in 30 wt% KOH solution. Further experimental results reveal that the FeOxHy@Ni3B/NF is endowed with superhydrophilic and superaerophobic surface properties, which not only provide more mass transport channels, as well as facilitated the diffusion of reaction intermediates and gas bubbles. Also, it holds faster reaction kinetics, more accessible active sites and accelerated electron transfer rates due to strong synergistic interactions at the heterogeneous interface.

All-Solid-State Supercapacitors Based on Cobalt Magnesium Telluride Microtubes Decorated with Tellurium Nanotubes.

Magnesium (Mg) has received very little exploration on its importance in the realm of battery-type energy storage technologies. They are abundantly present in seawater, and if successfully extracted and utilized in energy storage systems, it could lead to the long-term advancement of human civilization. Here, we fabricated an all-solid-state supercapacitor (ASSSC) using tellurium nanotubes decorated cobalt magnesium telluride microtubes (Te NTs@CoMgTe MTs) clad on nickel foam (NF). Owing to the unique mixed phase hierarchical structure, Te NTs@CoMgTe MTs showcases some advancement in energy storage performance. When tested in a three-electrode system, multiphasic hybrid of elemental Te and metal tellurides, Te NTs@CoMgTe MTs outperforms the monometallic telluride owing to the strong synergistic interaction effect triggered from conductive three components and delivers a long-life span performance up to 15,000 cycles. The fabricated Te NT@CoMgTe MT//AC solid-state device exhibits a maximum areal capacity of 59.2 μAh cm-2 (56.3 mAh g-1) at a current density of 6 mA cm-2 with a maximum energy density of 42.2 Wh kg-1 (46.5 μWh cm-2) at a power density of 6857.1 W kg-1 (7574.6 μW cm-2). The performance of the device is rigid even at different bending angles (0 to 180°) which validates the extensibility of the process for future applications.

Synergistic enhancement of interfacial adhesion for CF/PEEK composites through carbene chemistry and water‐based self‐catalyzed cross‐linkable PENK‐NH2 sizing agent

AbstractTo address the issue of inadequate interfacial adhesion in carbon fiber/poly ether ether ketone (CF/PEEK) composites, an innovative approach that combines carbene chemistry and sizing treatment was meticulously designed to achieve remarkable synergistic enhancement. Specifically, cyano groups were chemical‐grafted on CF surface via carbene reaction. Meanwhile, a water‐based self‐catalyzed cross‐linkable PENK‐NH2 sizing agent with good storage stability was prepared. Noteworthy, the presence of amino groups as blocking agents of sizing agent significantly accelerated the rate of cyano‐crosslinking, thus effectively avoiding the adverse effects of excessively prolonged cross‐linking period during composites preparation. As a result, robust interaction between cyano‐modified CF and PEEK was established by cross‐linking reaction, along with chemical bonds generated between amino groups of sizing agent and ketone groups in PEEK. The maximum interlaminar shear strength (ILSS) of CF‐CN‐1.5/PEEK composites was 22.0% and 57.0% higher than CF‐1.5/PEEK and CF/PEEK composites. Furthermore, the presence of cyano‐cross‐linked structure endowed interphase with outstanding solvent‐resistance, the mechanical properties of CF composites after solvent treatment were well‐preserved. The strong synergistic interfacial interactions facilitated by chemical bonds in different components provide an effective and fascinating methodology for producing high‐performance CF/composites.Highlights Water‐based self‐catalyzed cross‐linkable PENK‐NH2 sizing agents for CF/PEEK were prepared. NH2 was introduced to avoid the adverse effects of prolonged cyano‐crosslinking. Designed carbenoid motif with cyano group was grafted on CF via carbene chemistry. The interaction between sizing agent and CF was boosted by the cyano‐crosslinking. Mechanical properties of sized composites corroded by solvent were well‐preserved.

Heterointerface and crystallinity engineering of Ru/RuS2 dual co-catalysts for enhanced photocatalytic hydrogen evolution

In this paper, the Ru/RuS2 nanoparticles as dual co-catalysts were self-assembled on the surface of g-C3N4 nanotubes (Ru/RuS2/g-C3N4 NTs) for photocatalytic H2 production. The Ru/RuS2/g-C3N4 NTs showed greatly enhanced photocatalytic H2 production activity (1409 μmol·g−1·h−1), 1.16 times of RuS2/g-C3N4 NTs (1212 μmol·h−1·g−1), 10.51 times of Ru/g-C3N4 NTs (134 μmol·g−1·h−1), and 82.88 times of the pure g-C3N4 NTs (17 μmol·g−1·h−1). Besides, the apparent quantum yield value (AQE) of Ru/RuS2/g-C3N4 NTs is 3.92% at 370 nm. Ru/RuS2 as dual co-catalysts are self-assembled on the surface of g-C3N4 NTs and show strong electronic synergistic interaction between the interfaces, reduce ΔGH* of RuS2 and desorption energy of Ru, and promote the selectivity and activity of HER kinetically and thermodynamically respectively, which exhibits higher photogenerated carrier concentration and lower charge migration resistance than RuS2 and Ru, showing the synergistic effect to facilitate the generation and migration of carriers and provides active sites for photocatalysis.

Fe-Ni bimetallic atomic catalysts supported on ZIF-8 derived carbon for C3H6-SCR of NO: Catalytic performance and reaction mechanism

N-doped hollow carbon derived from ZIF-8 was utilized as a carrier to prepare the atomically dispersed Fe-Ni bimetallic catalysts, i.e., (Fe, Ni)/NC. The reactivity of C3H6-SCR was evaluated. The strong synergistic interactions between Fe and Ni promoted the activity of C3H6-SCR at low temperatures under different oxygen conditions (0–6 % O2). The NO conversion increased from 74.5 % to 93 % in the 150–300 °C and the N2 selectivity was about 95.5 %. The dual-atom catalysts were characterized by SEM, EELS, XRD, XPS, FTIR, and N2 adsorption/desorption, as well as the AC-HAADF-STEM, XANES, EXAFS, and Wavelet Transform data, etc. Results showed that (Fe, Ni)/NC catalyst showed the rhombic dodecahedral and displayed type IV isotherms with prominent H4 hysteresis loop, suggesting the loading of Fe and Ni atoms on the carbon matrix resulted in the coexistence of micropores and mesopores. Bimetallic active sites can enhance catalytic activity. As reflected by the Fe K-edge EXAFS spectra with k2-weighted Fourier-transform (FT) in R-space, the coordination of active sites Fe-N and Fe-Ni appeared at 1.50 Å and 2.3 Å, respectively. Similarly, the Ni-N and Ni-Fe coordination were found to be positioned at 1.4 Å and 2.3 Å, respectively. The XANES and EXAFS data further confirmed that the (Fe, Ni)/NC catalysts existed in the unique bimetallic active site of the N3-Fe-Ni-N3. In situ DRIFTS showed O2 could promote the production of nitrate and CxHyOz substances, e.g., acetaldehyde and acetate, at Fe-Ni sites or surface defective oxygen sites. Nitrate and acetate species are the main active substances of C3H6-SCR.

Heterostructured FeSe2-CoSe2 Nanorods Supported on Nitrogen and Sulfur co-doped Reduced Graphene Oxide as High‐Performance Electrocatalyst for Oxygen Evolution Reaction

With the aim of hydrogen production from electrochemical water splitting on a high scale, the core challenge is to develop an effective oxygen evolution reaction (OER) electrocatalyst with high activity as well as a low cost. Herein, we developed a heterostructure of Iron and cobalt selenide supported by a dual heteroatom (Nitrogen and Sulphur) doped reduced graphene oxide, synthesized by an easy solvothermal method. The as-synthesized CoSe2-based catalyst consists of urchin-like assembled nanorods resulting in the highly exposed reaction sites and shows excellent electrochemical performance with the much lowest overpotentials of 216 mV and 291 mV at a current density of 10 and 50 mA cm−2, respectively, Tafel slope of 53.4 mV dec−1 and long-term stability for 50 h in an alkaline environment. As a result, the improved OER activity of the as-synthesized electrocatalyst could be attributed to the highly accessible heterointerfaces served as abundant catalytic active sites as well as strong synergistic interaction and enhanced electrical conductivity that increased the movement of electron transfer. The achieved results manifest the superiority of the prepared electrocatalyst towards OER and it can be a remarkable electrocatalyst which is helpful for further development in the practical application of water splitting to decrease energy utilization at a high scale.

Tern-701 (HS-10382) Is a Potent Inhibitor of BCR::ABL1 and Is Synergistic with Active Site Tyrosine Kinase Inhibitors

CONCLUSIONS Although tyrosine kinase inhibitors (TKIs) targeting the ATP-binding site of the BCR::ABL1 oncoprotein are effective therapeutics for chronic myeloid leukemia (CML), patients often develop drug resistance due to ATP-site mutations that inhibit drug binding. TERN-701 is a potent and highly selective inhibitor of BCR::ABL1 that is designed to bind the allosteric myristoyl site on the kinase, circumventing resistance to active site mutations, with potential for synergistic combination with active site TKIs. Competition binding screens were used to assess the selectivity of TERN-701 on more than 450 targets spanning the human kinome. The potency of TERN-701 against the proliferation of wild type and mutant CML cell lines, as well as a panel of 102 cancer cell lines, was assessed using CellTiter-Glo®. Synergy between TERN-701 and active site TKIs was assessed in vitro with interactions quantified using Bliss, combination, and curve-shift analyses. Prospective mutagenesis experiments were conducted by treating BaF/3 cells engineered to overexpress the BCR::ABL1 kinase with various concentrations of both TERN-701 and the TKI imatinib, followed by observation of clonal outgrowth of treated cells over time. We have previously shown that TERN-701 is a potent inhibitor of native CML cell lines such as K562. Here, we show that TERN-701 inhibited cell proliferation in various clinically relevant mutant CML cell lines (including T315I) with IC 50s ranging from 5 to 26 nM and 70 to 1200 nM against active site and myristoyl site mutations, respectively. TERN-701 was highly selective for BCR::ABL1, with no appreciable activity (&amp;gt;50%) against &amp;gt;450 purified kinase targets. Against a panel of cancer cell lines, TERN-701 was more selective than the comparator allosteric BCR::ABL1 inhibitor asciminib while maintaining similar potency. In vitro combination studies previously revealed that TERN-701 works synergistically with multiple TKIs in the non-mutant K562 cell line. Here, expanded studies using KCL22-s and BCR::ABL1-T315I mutant cell lines identified strong synergistic interactions between TERN-701 and active site TKIs, including ponatinib and dasatinib. Furthermore, prospective mutagenesis studies showed that the combination of TERN-701 and imatinib resulted in greater inhibition of the outgrowth of resistant clones relative to either compound alone. TERN-701 is a potent and highly selective allosteric inhibitor of BCR::ABL1 that can act synergistically with active site TKIs in vitro, even against the T315I gatekeeper mutation that confers resistance to all approved active site TKIs except ponatinib, which has known safety liabilities. These data support the continued development of TERN-701 for the treatment of CML using both monotherapy and combination approaches.

Venetoclax Synergizes Sunitinib in Renal Cell Carcincoma through Inhibition of Bcl-2.

More effective treatment options for patients with renal cell carcinoma (RCC) are needed, in particular advanced RCC. Sunitinib, a multitarget tyrosine kinase inhibitor, is a first-line treatment of metastatic RCC. However, the management of sunitinib-induced adverse events and resistance is complex. In hematological malignancies, effective targeting of anti-apoptotic proteins such as Bcl-2 has been achieved, but limited progress has been made in solid tumors. This work systematically investigated the therapeutic potential of the combination of sunitinib and venetoclax, a Bcl-2 inhibitor, in preclinical RCC models. Quantitative analysis of drug interactions was performed. Cell viability was examined after drug treatment or Bcl-2 siRNA depletion. RCC xenograft mouse model was applied to validate the efficacy of sunitinib and venetoclax. A strong synergistic interaction between sunitinib and venetoclax was observed across a range of different dose levels in all tested RCC cell lines. Sequential treatment studies show that the sequential addition of venetoclax and then sunitinib is superior to concurrent treatment and the sequential addition of sunitinib and then venetoclax in decreasing RCC cell viability. The sensitivity of RCC cell lines to venetoclax treatment negatively correlates with their Bcl-2 levels. Specific depletion of Bcl-2 mimics the synergistic effects of venetoclax with sunitinib. Treatment of mice implanted with high Bcl-2-expressing RCC cells reveals that a combination of venetoclax and sunitinib at a non-toxic dose displays complete regression of tumor growth throughout the whole duration of treatment. Our work demonstrates that inhibiting Bcl-2 by venetoclax synergistically enhances sunitinib's efficacy in RCC. Venetoclax holds great potential as a viable option for clinical use.

Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells

Colon cancer is a major cause of cancer-related death. Despite recent improvements in the treatment of colon cancer, new strategies to improve the overall survival of patients are urgently needed. Heat shock protein 90 (HSP90) is widely recognized as a promising target for treating various cancers, including colon cancer. However, no HSP90 inhibitor has been approved for clinical use due to limited efficacy. In this study, we evaluated the antitumor activities of HSP90 inhibitors in combination with piperlongumine in colon cancer cells. We show that combination treatment with HSP90 inhibitors and piperlongumine displayed strong synergistic interaction in colon cancer cells. These agents synergize by promoting ER stress, JNK activation, and DNA damage. This process is fueled by oxidative stress, which is caused by the accumulation of reactive oxygen species. These studies nominated piperlongumine as a promising agent for HSP90 inhibitor-based combination therapy against colon cancer.