Reverse Activity Research Articles

Reciprocal tumor-platelet interaction through the EPHB1-EFNB1 axis in the liver metastatic niche promotes metastatic tumor outgrowth in pancreatic ductal adenocarcinoma.

The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation. Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver. However, the role of platelet in the liver metastatic niche of PDAC remains elusive. This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC. An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC. Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis. Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1 (Ephb1), tumor cell-platelet adhesion, recombinant protein, and tryptophan hydroxylase 1 (Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche. The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients. Platelet depletion decreased liver metastatic tumor growth in mice. Mechanistically, tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1 (EFNB1) mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation, and in turn, activated platelet-released 5-HT, further enhancing tumor growth. We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC. Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver. Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.

Optimizing Oxygen Redox Activity by Local Chemical Disorder toward Robust Co-Free Li-Rich Cathode with High Voltage Stability.

Despite extensive investigation on the lattice oxygen redox (LOR) in Li-rich cathodes, significant challenges remain in utilizing LOR activity without compromising structural and electrochemical stability. Related breakthroughs are hindered by the lack of understanding regarding how different LOR activity influences the structural evolution and electrochemical stability, and what is the optimal LOR activity. Herein, the degree of LOR activity is successfully regulated from 22% to 92% in Co-free Li-rich cathodes (Li1+xMn0.62Ni0.18O2) by controlling local chemical disorder, and the relationship between LOR activity and cycling stability is revealed. Conventional consensus is challenged by new findings that the over-suppressive LOR activity also undermines electrochemical/structural stability, and even causes more severe voltage fading compared to cases with excessive LOR. However, their failure mechanisms related to lattice strain present different characteristics. Based on the established understanding, the appropriate LOR activation is necessary to balance the maximum reversible LOR activity and good stability, and the optimal degree is identified as 86% in Li1.18Mn0.62Ni0.18O2 (LR-78). LR-78 exhibits remarkable voltage retention of 96% after 400 cycles at 1 C, and superior high-rate cyclability without capacity decay within 600 cycles at 5 C. These findings significantly broaden the understanding of LOR mechanisms and provide critical guidance for designing durable LOR-based cathodes.

Unmasking the reverse catalytic activity of 'ene'-reductases for asymmetric carbonyl desaturation.

Carbonyl desaturation is a fundamental reaction widely practised in organic synthesis. While numerous methods have been developed to expand the scope of this important transformation, most of them necessitate multi-step protocols or suffer from the use of high loadings of metal or strong oxidizing conditions. Moreover, approaches that can achieve precise stereochemical control of the desaturation process are extremely rare. Here we report a biocatalytic platform for desymmetrizing desaturation of cyclohexanones to generate diverse cyclohexenones bearing a remote quaternary stereogenic centre, by reengineering 'ene'-reductases to efficiently mediate dehydrogenation, the reverse process of their native activity. This 'ene'-reductase-based desaturation system operates under mild conditions with air as the terminal oxidant, tolerates oxidation-sensitive or metal-incompatible functional groups and, more importantly, exhibits unparalleled stereoselectivity compared with those achieved with small-molecule catalysts. Mechanistic investigations suggest that the reaction proceeded through α-deprotonation followed by a rate-determining β-hydride transfer.

Direct Formation of Todorokite Mn Oxide Via Electrodeposition

Todorokite, a manganese oxide with a 3 × 3 tunnel structure (~1 nm), has attracted interest for its potential application in energy storage, desalination, sensor, and catalyst, owing to its reversible ion exchange capacity and catalytic activity. However, conventional synthesis of todorokite involves a time- and energy consuming three-step process: (1) precipitation of a layered Mn oxide, (2) intercalation of Mg2+ into the layer, and (3) transformation to todorokite via hydrothermal reaction. In this study, we propose a novel method for the direct formation of todorokite within 30 minutes using 1 M MgCl2 electrolyte with Mn2+(aq) at pH 8.5 via electrodeposition. Our electrochemical approach enabled the formation of todorokite by stabilizing structured Mn(III), which induces Jahn-Teller distortion and structural rearrangement to form tunnel, through precise adjustment of pH and concentration of Mg2+. Notably, we confirmed, through computational calculations and experimental results, the significant changes in Mn(III) within Mn oxides approximately pH 7.4, as well as range of Mg(OH)+ concentrations that stabilize Mn(III) for todorokite formation. Our electrochemically mediated method not only facilitates the synthesis of todorokite but also provides specific insights into the mechanisms of its direct formation.

A highly-proton conductive poly(vinyl alcohol)/silica nanocomposite membrane for PANI@GNP symmetric supercapacitor separator

Polyaniline (PANI) has potential as an anode and cathode for proton based batteries (PBs) owing to its high energy density (295 mAh g−1) and excellent reversible redox activity. Achieving proton electrolytes with fast single-proton conduction behavior, separator-required mechanical properties and good proton transport channel is essential but extremely challenging for the practical success of PBs. Herein, this proton separator is constructed with nano-silica grid points in polyvinyl alcohol (PVA) chains cross-linked by sulfuric acid. Results show that PVA/inorganic composite proton membrane (PIC-PM) can immobilize the sulfate anions and help dissociate H+, which leads to a high ionic conductivity (8.6 × 10−2 S cm−1). Moreover, PIC-PM shows enough toughness and mechanical strength to puncture resistance. When the PIC-PM was applied to assemble a PANI@GNP symmetric supercapacitor, it delivers a high capacity of 943.1 F/g at 0.5 A/g; a rate capability of 74.9 % with the current density increasing from 0.5 to 5 A/g; and a capacity retention rate of 84.3 % after 1000 cycles in a current density of 3.5 A/g.

Parameter Analysis of Anion Exchange Membrane Water Electrolysis System by Numerical Simulation

Anion exchange membrane electrolysis, which combines the advantages of both alkaline electrolysis and proton-exchange membrane electrolysis, is a promising technology to reduce the cost of hydrogen production. The present work focused on the study of the electrochemical phenomena of AEM electrolysis and the investigation of the key factors of the AEM hydrogen production system. The numerical model is established according to electrochemical reactions, polarization phenomena, and the power consumption of the balance of plant components of the system. The effects of operation parameters, including the temperature and hydrogen pressure of the electrolyzer, electrolyte concentration, and hydrogen supply pressure on the energy efficiency are studied. The basic electrochemical phenomena of AEM water electrolysis cells are analyzed by simulations of reversible potential and activation, and ohmic and concentration polarizations. The results reveal that increasing the operating temperature and hydrogen production pressure of the AEM electrolyzer has positive effects on the system’s efficiency. By conducting an optimization analysis of the electrolyzer temperature—which uses the heat energy generated by the electrochemical reaction of the electrolyzer to minimize the power consumption of the electrolyte pump and heater—the AEM system with an electrolyzer operating at 328 K and 30 bar can deliver hydrogen of pressure up to 200 bar under an energy efficiency of 56.4%.

Model benchmarking for PEM Water Electrolyzer for energy management purposes

This research conducts a comprehensive evaluation of various Proton Exchange Membrane Water Electrolyzer (PEMWE) models through a test bench, optimizing parameters and comparing obtained models against real-world data. Key operational factors such as reversible potential, activation overpotential, ohmic overpotential, and concentration overpotential are examined through experimental data. This study addresses critical gaps in current PEMWE research by reviewing modelling approaches, introducing a novel classification of models, and proposing an integrated approach that combines experimental validation with comprehensive model analysis. A novel, systematic methodology for model and submodel selection is presented, enabling practitioners to identify models that balance computational efficiency and predictive accuracy tailored to specific energy management and power allocation needs. This approach bridges the gap between complex modelling and industrial applications, enhancing the practical implementation of PEMWE systems in sustainable hydrogen production. Enhances model reliability for operational and manufacturing differences, provides invaluable guidance for improving the design and operation of these systems, and promotes a more robust and efficient hydrogen energy infrastructure.

Requirement of Bacillus subtilis succinate:menaquinone oxidoreductase activity for membrane energization depends on the direction of catalysis

Succinate:quinone oxidoreductases (SQR) from Bacilli catalyze reduction of menaquinone by succinate, as well as the reverse reaction. The direct activity is energetically unfavorable and lost upon ΔμН+ dissipation, thus suggesting ΔμН+ to be consumed during catalysis. Paradoxically, the generation of ΔμН+ upon fumarate reduction was never confirmed. Thus, the exact role of ΔμН+ in the operation of bacillary-type SQRs remained questionable. The purpose of this work was to clarify this issue.We have described the different operating modes of the membrane-bound SQR from Bacillus subtilis. Tightly coupled membrane vesicles from both wild-type cells and the mutant containing cytochrome bd as the only terminal oxidase were studied. This made it possible to compare the respiratory chains with 2 versus 1H+/e− stoichiometry of ΔμН+ generation. Direct and reverse activities of SQR were determined under either energized or deenergized conditions.The wild-type membranes demonstrated high succinate oxidase activity very sensitive to uncoupling. On the contrary, the mutant showed extremely low succinate oxidase activity resistant to uncoupling. ΔμН+ generation at the cost of ATP hydrolysis restored the uncoupling sensitive succinate respiration in the mutant. Membranes of the both types effectively reduced fumarate by menaquinol. This activity was not affected by energization or uncoupling, neither it was followed by ΔμН+ generation.Thus, B. subtilis SQR demonstrates two regimes: ΔμН+-coupled and not coupled. This behavior can be explained by assuming the presence of two menaquinone binding sites which drastically differ in affinity for the oxidized and reduced substrate.

Chiral Co-assembly Based on a Stimuli-Responsive Polymer towards Amplified Full-Color Circularly Polarized Luminescence.

Stimuli-responsive circularly polarized luminescence (CPL) materials have been attaching wide attention in the field of optical information storage and encryption, while still facing the challenge of the realization of high luminescence dissymmetry factors (glum). This work presents a pair of stimuli-responsive chiral co-assemblies P7R3 and P7S3 by combining polymer PFIQ containing iso-quinoline units with chiral inducers. The obtained chiral co-assemblies can reversibly undergo significant modification in CPL behavior under trifluoroacetic acid (TFA) fumigation and annealing treatment, with the |glum| values exhibiting a reversible shift between 0.2 and 0.3. Moreover, the chiral co-assemblies before TFA fumigating can effectively induce achiral emitters to generate intense full-color CPL signals through CPL energy transfer (CPL-ET), with the corresponding |glum| values larger than 0.2. Moreover, information encryption and decryption as well as a multi-level logic gates application are achieved by leveraging the reversible stimuli-responsive CPL activity of the chiral co-assembly. This work provides a new perspective for the construction of stimuli-responsive chiral luminescent materials with large |glum| values and the activation of CPL behavior in achiral emitters.

A Rationally Designed Azobenzene Photoswitch for DNA G-Quadruplex Regulation in Live Cells.

G-quadruplex (G4) DNA structures are increasingly acknowledged as promising targets in cancer research, and the development of G4-specific stabilizing compounds may lay a fundamental foundation in precision medicine for cancer treatment. Here, we propose a light-responsive G4-binder for precise modulation of drug activation, providing dynamic and spatiotemporal control over G4-associated biological processes contributing to cancer cell death. We developed a specialized fluorinated azobenzene (AB) switch equipped with a quinoline unit and a positively charged carboxamide side chain, Q-Azo4F-C, designed for targeted binding to G4 structures within cells. Biophysical studies, combined with molecular dynamics simulations, provide insights into the unique coordination modes of the photoswitchable ligand in its trans and cis configurations when interacting with G4s. The observed variations in complexation processes between the two isomeric states in different cancer cell lines manifest in more than 25-fold reversible cytotoxic activity. Immunostaining conducted with the structure-specific G4 antibody (BG4), establishes a direct correlation between cytotoxicity and the varying extent of G4 induction regulated by the two isoforms. Finally, we demonstrate the photo-driven reversible regulation of G4 structures in lung cancer cells by Q-Azo4F-C. Our findings highlight the potential of light-responsive G4-binders in advancing precision cancer therapy through dynamic control of G4-mediated pathways.

Immobilization β-glucosidase from Dictyoglomus thermophilum on UiO-66-NH2: An efficient catalyst for enzymatic synthesis of kinsenoside via reverse hydrolysis reaction

Kinsenoside is a rare and valuable glycoside with extensive bioactivities. However, the enzymatic synthesis of kinsenoside has been a challenging task due to the limited enzyme toolbox and unsatisfactory yield. Herein, the β-glucosidase from Dictyoglomus thermophilum (DtBGL) was heterologously expressed, purified and enzymatically characterized. The purified DtBGL was successfully immobilized on the metal-organic frameworks of UiO-66-NH2. The DtBGL@UiO-66-NH2 was fully characterized using SEM, XRD, TGA and FTIR. The studies on enzymatic properties demonstrated that DtBGL@UiO-66-NH2 exhibited increased catalytic activity and stability compared to the free DtBGL. Particularly, DtBGL@UiO-66-NH2 could catalyze the synthesis of kinsenoside via the reverse hydrolysis reaction and the kinsenoside yield was 34.12 % under the optimized catalytic system, which was 1.9-fold higher compared with the free DtBGL. Moreover, DtBGL@UiO-66-NH2 displayed good reusability with a kinsenoside yield of 27.02 % after reuse for 3 times. The present work not only identifies and characterizes a highly active β-glucosidase with reverse hydrolysis activity, but also proposes the immobilized enzyme as an effective catalyst for the industrial production of glycosides.

A Rationally Designed Azobenzene Photoswitch for DNA G‐Quadruplex Regulation in Live Cells

AbstractG‐quadruplex (G4) DNA structures are increasingly acknowledged as promising targets in cancer research, and the development of G4‐specific stabilizing compounds may lay a fundamental foundation in precision medicine for cancer treatment. Here, we propose a light‐responsive G4‐binder for precise modulation of drug activation, providing dynamic and spatiotemporal control over G4‐associated biological processes contributing to cancer cell death. We developed a specialized fluorinated azobenzene (AB) switch equipped with a quinoline unit and a positively charged carboxamide side chain, Q‐Azo4F‐C, designed for targeted binding to G4 structures within cells. Biophysical studies, combined with molecular dynamics simulations, provide insights into the unique coordination modes of the photoswitchable ligand in its trans and cis configurations when interacting with G4s. The observed variations in complexation processes between the two isomeric states in different cancer cell lines manifest in more than 25‐fold reversible cytotoxic activity. Immunostaining conducted with the structure‐specific G4 antibody (BG4), establishes a direct correlation between cytotoxicity and the varying extent of G4 induction regulated by the two isoforms. Finally, we demonstrate the photo‐driven reversible regulation of G4 structures in lung cancer cells by Q‐Azo4F‐C. Our findings highlight the potential of light‐responsive G4‐binders in advancing precision cancer therapy through dynamic control of G4‐mediated pathways.

ATP-Triggered Fe(CN)2CO Synthon Transfer from the Maturase HypCD to the Active Site of Apo-[NiFe]-Hydrogenase.

[NiFe]-hydrogenases catalyze the reversible activation of H2 using a unique NiFe(CN)2CO metal site, which is assembled by a sophisticated multiprotein machinery. The [4Fe-4S] cluster-containing HypCD complex, which possesses an ATPase activity with a hitherto unknown function, serves as the hub for the assembly of the Fe(CN)2CO subfragment. HypCD is also thought to be responsible for the subsequent transfer of the iron fragment to the apo-form of the catalytic hydrogenase subunit, but the underlying mechanism has remained unexplored. Here, we performed a thorough spectroscopic characterization of different HypCD preparations using infrared, Mössbauer, and NRVS spectroscopy, revealing molecular details of the coordination of the Fe(CN)2CO fragment. Moreover, biochemical assays in combination with spectroscopy, AlphaFold structure predictions, protein-ligand docking calculations, and crosslinking MS deciphered unexpected mechanistic aspects of the ATP requirement of HypCD, which we found to actually trigger the transfer of the Fe(CN)2CO fragment to the apo-hydrogenase.

Crystal Modulation of Mn-Based Layered Oxide toward Long-Enduring Anionic Redox with Fast Kinetics for Sodium-Ion Batteries.

Mn-based layered oxide cathodes for sodium-ion batteries with anionic redox reactions hold great potential for energy storage applications due to their ultra-high capacity and cost effectiveness. However, achieving high capacity requires overcoming challenges such as oxygen-redox failure, sluggish kinetics, and structural degradation. Herein, we employ an innovative crystal modulation strategy, using Mn-based Na0.72Li0.24Mn0.76O2 as a representative cathode material, which shows that the highly exposed {010} active facets enable an enhanced rate capability (119.6 mAh g-1 at 10C) with fast kinetics. Meanwhile, the reinforced Mn-O bond inhibits excessive oxidation of lattice oxygen and O-O cohesion loss, stabilizing and maintaining a long-enduring reversible oxygen-redox activity (100% high capacity retention after 100 cycles at 0.5C and 84.28% retention after 300 cycles at 5C). Time-resolved operando two-dimensional X-ray diffraction reveals the robust structural stability, zero-strain behavior, and suppressed phase transition with ultra-low volume variation during cycling at different rates (0.1C: 1.75%, 1C: 0.31%, 5C: 0.04%). Additionally, the full cell coupled with hard carbon achieves a high energy density of approximately 211 Wh kg-1 with superior performance. This work highlights the significance of crystal modulation and presents a universal approach in developing Mn-based oxide cathodes with stable anionic redox for high-performance sodium-ion batteries.

Integrating Multiple Redox‐Active Units into Conductive Covalent Organic Frameworks for High‐Performance Sodium‐Ion Batteries

AbstractThe rational design of porous covalent organic frameworks (COFs) with high conductivity and reversible redox activity is the key to improving their performance in sodium‐ion batteries (SIBs). Herein, we report a series of COFs (FPDC‐TPA‐COF, FPDC‐TPB‐COF, and FPDC‐TPT‐COF) based on an organosulfur linker, (trioxocyclohexane‐triylidene)tris(dithiole‐diylylidene))hexabenzaldehyde (FPDC). These COFs feature two‐dimensional crystalline structures, high porosity, good conductivity, and densely packed redox‐active sites, making them suitable for energy storage devices. Among them, FPDC‐TPT‐COF demonstrates a remarkably high specific capacity of 420 mAh g−1 (0.2 A g−1), excellent cycling stability (~87 % capacity retention after 3000 cycles, 1.0 A g−1) and high rate performance (339 mAh g−1 at 2.0 A g−1) as an anode for SIBs, surpassing most reported COF‐based electrodes. The superior performance is attributed to the dithiole moieties enhancing the conductivity and the presence of redox‐active carbonyl, imine, and triazine sites facilitating Na storage. Furthermore, the sodiation mechanism was elucidated through in situ experiments and density functional theory (DFT) calculations. This work highlights the advantages of integrating multiple functional groups into redox‐active COFs for the rational design of efficient and stable SIBs.

Integrating Multiple Redox-Active Units into Conductive Covalent Organic Frameworks for High-Performance Sodium-Ion Batteries.

The rational design of porous covalent organic frameworks (COFs) with high conductivity and reversible redox activity is the key to improving their performance in sodium-ion batteries (SIBs). Herein, we report a series of COFs (FPDC-TPA-COF, FPDC-TPB-COF, and FPDC-TPT-COF) based on an organosulfur linker, (trioxocyclohexane-triylidene)tris(dithiole-diylylidene))hexabenzaldehyde (FPDC). These COFs feature two-dimensional crystalline structures, high porosity, good conductivity, and densely packed redox-active sites, making them suitable for energy storage devices. Among them, FPDC-TPT-COF demonstrates a remarkably high specific capacity of 420 mAh g-1 (0.2 A g-1), excellent cycling stability (~87 % capacity retention after 3000 cycles, 1.0 A g-1) and high rate performance (339 mAh g-1 at 2.0 A g-1) as an anode for SIBs, surpassing most reported COF-based electrodes. The superior performance is attributed to the dithiole moieties enhancing the conductivity and the presence of redox-active carbonyl, imine, and triazine sites facilitating Na storage. Furthermore, the sodiation mechanism was elucidated through in situ experiments and density functional theory (DFT) calculations. This work highlights the advantages of integrating multiple functional groups into redox-active COFs for the rational design of efficient and stable SIBs.

Interaction law between mining stress and fault activation and the effect of fault dip angle in longwall working face

Study of the interaction between fault activation and mining stress evolution in the longwall working face is helpful to provide a targeted area for fault type heavy mine pressure disaster control. Combining theoretical analysis, physical and numerical simulation, the mechanical mechanism of fault activation is analyzed, the interaction law between mining stress and fault activation is studied, and the influence of fault dip angle on the evolution of fault activation and mining stress is discussed. The minimum critical dip angles α of normal and reverse fault activation are π/4 + φ/2 and π/4-φ/2, respectively. During the mining process, the activation position of the fault surface, the peak values of stress and displacement gradually increase and transfer from the high position of the fault to the low position, and the peak value of the advance abutment pressure reaches the maximum at the fault. The advancing distance of the working face required for fault activation gradually decreases with the decrease of the fault dip angle, and the peak elevation area of the working face gradually increases with the decrease of the fault dip angle. Combined with the on-site microseismic monitoring results, it can be seen that when the working face is about 20 m away from the fault, the stress and energy increase sharply, which is the main control area of the impact disaster.

Development of novel DNA aptamers and colorimetric nanozyme aptasensor for targeting multi-drug-resistant, invasive Salmonella typhimurium strain SMC25

Invasive, biofilm-forming Non-typhoidal Salmonella (iNTS), propagating through the global food and water supply chain, presents a significant risk to food safety and public health. Developing a robust detection system is crucial for enabling point-of-care, affordable, and equipment-free identification of this pathogen throughout the supply chain. In this study, we screened a novel pool of ssDNA aptamers specific to a multidrug resistant iNTS strain SMC25, previously isolated from Indian poultry products in our earlier research. Through 13 rounds of whole-cell SELEX, we identified, characterized, and selected seven full-length aptamers (ST18, ST19, ST25, ST28, ST29, ST31, and ST32). Flow cytometric analysis reveals superior binding of ST25, ST28, ST29, and ST31. These aptamers were translated onto Nanozyme-based aptasensing system for efficient, cost-effective detection of SMC25. This system harnesses the aptamer-mediated, reversible peroxidase-like activity of gold nanoparticles (GNPs) to oxidize the TMB substrate into a one-electron oxidation state, resulting in a blue-colored Diamine charge transfer complex (DCTC). The catalytic process, coupled with GNP aggregation, induces a visible color change in the test mixture from ruby-red to blue. Post-SELEX truncations identified the optimal aptamer sequence (T_ST31), which selectively detected SMC25 in water with a limit of detection (LOD) of ∼10⁴ CFU/mL. Lower concentrations (10 CFU/mL) of SMC25 could be detected after non-selective enrichment within 120 min. This research introduces a novel pool of iNTS-specific aptamers along with a cost-effective (0.25 USD per sample) solution for colorimetric detection by the naked eye.

High-performance α-Fe2O3 nano cubes as anode for supercapacitors

Abundant availability, high theoretical specific capacitance and low cost of transition metal oxides such as iron oxides, make them attractive as electrode materials for energy storage. In order to achieve improved performance, high conductivity, shorter ion-diffusion path, and faster ion accessibility, rational design of morphology of electrode material is highly desirable. We have successfully synthesized mesoporous α-Fe2O3 nanocubes to achieve high specific capacitance and better retention. The as-prepared and annealed α-Fe2O3 nanocubes show high reversible redox activity along with good thermodynamic stability. These nanostructure give rise to high specific capacitance and ~90 % of the capacitance can be retained even after 1000 redox cycles, suggesting good cyclic stability. The electrochemical performance of mesoporous α-Fe2O3 nanocubes is attributed to the morphological features, which results in efficient K+ ion transport into the pores. A two electrode α-Fe2O3//NiO device is fabricated, which shows excellent power and energy density of ∼627 W/kg and ∼23.32 Wh/kg, respectively. Our work demonstrates that 3D nanoporous α-Fe2O3 electrodes forms promising material system as anode for improved charge storage performance.

Soloxolone N-3-(Dimethylamino)propylamide Restores Drug Sensitivity of Tumor Cells with Multidrug-Resistant Phenotype via Inhibition of P-Glycoprotein Efflux Function.

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, primarily due to the overexpression of transmembrane drug transporters, with P-glycoprotein (P-gp) being a central focus. Consequently, the development of P-gp inhibitors has emerged as a promising strategy to combat MDR. Given the P-gp targeting potential of soloxolone amides previously predicted by us by an absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, the aim of the current study was to experimentally verify their P-gp inhibitory and MDR reversing activities in vitro. Screening of soloxolone amides as modulators of P-gp using molecular docking and cellular P-gp substrate efflux assays revealed the ability of compound 4 bearing a N-3-(dimethylamino)propylamide group to interact with the active site of P-gp and inhibit its transport function. Blind and site-specific molecular docking accompanied by a kinetic assay showed that 4 directly binds to the P-gp transmembrane domain with a binding energy similar to that of zosuquidar, a third-generation P-gp inhibitor (ΔG = -10.3 kcal/mol). In vitro assays confirmed that compound 4 enhanced the uptake of Rhodamine 123 (Rho123) and doxorubicin (DOX) by the P-gp-overexpressing human cervical carcinoma KB-8-5 (by 10.2- and 1.5-fold, respectively (p < 0.05, unpaired t-test)) and murine lymphosarcoma RLS40 (by 15.6- and 1.75-fold, respectively (p < 0.05, unpaired t-test)) cells at non-toxic concentrations. In these cell models, 4 showed comparable or slightly higher activity than the reference inhibitor verapamil (VPM), with the most pronounced effect of the hit compound in Rho123-loaded RLS40 cells, where 4 was 2-fold more effective than VPM. Moreover, 4 synergistically restored the sensitivity of KB-8-5 cells to the cytotoxic effect of DOX, demonstrating MDR reversal activity. Based on the data obtained, 4 can be considered as a drug candidate to combat the P-gp-mediated MDR of tumor cells and semisynthetic triterpenoids, with amide moieties in general representing a promising scaffold for the development of novel therapeutics for tumors with low susceptibility to antineoplastic agents.