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Create Li-ion multichannels and achieve excellent ionic conductivity by doping cost-effective Fe2+ in halospinel.

A sodium polyacrylate (NaPAA) binder induces the formation of a stable and Na-ion conductive NaPO2F2-rich cathode–electrolyte interphase layer via a displacement reaction.

A structure-mechanism-performance relationship of metal-free carbon catalysts for outstanding H2O2 production activity and selectivity in alkaline media.

Controllable synthesis of graphene-coated metal nanoparticles (NPs) presents a major challenge when considering the practical application of these catalysts. Herein, we use silica as a radical sieve to grow graphene over cobalt NPs via chemical vapor deposition. As-prepared single-layer graphene-coated cobalt NPs with and without N doping (Co@N-SG and Co@SG) exhibit noticeable oxygen evolution reaction (OER) activity. Furthermore, a magnet-assisted binder-free Co@N-SG electrode illustrates much improved OER activity and stability over conventional binder-assisted counterparts, suggesting this as an effective way to overcome the recognized issues of high electron transfer resistance and poor adhesion of binder-based electrodes in practical applications. Interestingly, the graphene shell possesses varying defects and major OER benefitting active sites are found around said defects in the shell, while separately isolated Co@SG with a defect-free shell, despite exhibiting a slightly lower initial activity, illustrates a much-improved durable OER performance. The underlying Co affects the electron density of the graphene shell through dipole interaction and the electron density is optimized for adsorption of reaction intermediates, hence accelerating OER performance. This work will provide new clues to design efficient and durable electrocatalysts with further enhanced OER performance.

A solid-state electrolyte (SSE) is a key component in the performance control of all-solid-state Li-ion batteries. The development of a promising material has, however, come to a standstill due to the undesirably low ionic conductivity and stability. Using first-principles calculations, we propose that halospinels, i.e., Li2Sc2/3X4 (X = Cl, Br, and I), should be encouraging materials to surmount the long-standing challenges. Density functional theory (DFT) calculations unveil their underlying mechanisms that the incorporated halogen anion and Sc form unique ionic pairs to create the atomic environment required for the dramatic facilitation of Li-ion diffusion to a superionic conductor level. In addition, collective ionic motions near the halogen species in the halospinel solid electrolyte promote the substantial enhancement of the electrochemical stability and interface compatibility with the electrodes. We demonstrate that a crucial factor is the rational selection of the halogen anion to achieve the maximal performance of the electrolyte. Ab initio molecular dynamics (AIMD) simulations consistently pinpoint that the halospinel with Cl anion, Li2Sc2/3Cl4, is the best choice to maintain the high functionality of Li-ion conductivity, electrochemical stability, and interface compatibility with the LiCoO2 electrode in Li-ion battery applications. Our study provides a fundamental ground on chemical design principles for a breakthrough in advancing solid-state electrolytes towards a wide commercialization of all-solid-state Li-ion batteries.

To acquire a crystal-clear structure-performance relation for heterogeneous nanocatalysts, precise tracking of the structural evolution from the precursor to final product in the real time and space domain is important but also extremely challenging. In archetype preparation, thermal treatment is a crucial step for activation. Especially, for colloidally synthesized nanoparticles, the ligand detachment process to expose surfaces is completed with thermal treatment. Here, we track the three-dimensional atomic structural change of ligand-protected platinum nanoparticles under ligand detachment and thermal annealing processes. The structural transformation with time is shown by experimental decoupling and tracking of each atomic coordinate through molecular dynamics simulations with machine-learning potentials. Acquisition of structural data is integrated with a computational catalysis framework to identify a structure-activity correlation in the CO oxidation reaction. We find that colloidally synthesized platinum nanoparticles create unique atomic tensile strain and that varying the particle size tunes the ensemble effect of active sites.

Composites of different semiconductors are found to show much improved electronic conductivity and decreased charge transfer resistance. In this work, this hypothesis is tested by preparing composi...

Nickel foam (NF) can be directly utilized as an electrochemical electrode because of its conductive, rigid and porous structure. Herein, a novel robust binder-free Fe–Ni hydroxide-loaded NF electrode is prepared by simple corrosion of NF in a home-made piranha solution with an Fe3+ precursor. The roughened NF surface observed after the sample treatment indicates the formation of active species associated with amorphous Fe-hydroxide and/or FeNi-hydroxide particles. The piranha solution-corroded NF electrode generates more hydroxide groups compared to the water-corroded NF electrode, and exhibits remarkable electrochemical oxygen evolution reaction activity in alkaline medium with a low overpotential of 245 mV at 10 mA cm−2. It also maintains low working potential below 267 mV at 10 mA cm−2 over 500 h operation without any sign of degradation, indicating excellent long-term stability, which can be attributed to the robust binder-free electrode and the cooperative synergistic interaction between Fe-hydroxides and Ni-hydroxides in the FeNi hybrid composite of individually incompetent OER components, generated over the NF. The role of Fe doped in Ni(OH)2 is theoretically studied by DFT calculations, and it is found that the adsorption free energies of OH* and OOH* are significantly reduced by the addition of Fe into Ni(OH)2, accelerating the OER compared to bare Ni(OH)2. Furthermore, when the active electrode is equipped with a solar cell, a high current density of 23–24 mA cm−2 is observed for 10 h under AM 1.5G 1 sun irradiation, suggesting high possibility for the production of green hydrogen from renewable solar energy.

Transition metal single atom catalysts have recently emerged in acid oxygen evolution reactions (OER) due to their maximum atomic efficiency and high durability. Herein, we report a 3d orbital level rearrangement in square planar symmetry according to the ligand type of a cobalt single atom catalyst. We fabricate cobalt single atom catalyst supported on pyrrole type nitrogen doped crumpled graphene (Pyrrolic CoN4-CG) for acidic OER and it shows orbital rearrangement phenomenon because of their longer Co-N bond distance than pyridine type CoN4 sites. When pyrrole type nitrogen is introduced as a ligand of a cobalt single atom catalyst, the degree of oxidation during OER reaction is much greater than when pyridine type nitrogen ligand is introduced, which is confirmed by Operando X-ray absorption spectroscopy measurements. In addition, the reduction of OH- adsorption energy according to the orbital level rearrangement of Pyrrolic CoN4 and the change in the rate determination step are revealed by density functional theory calculations.

Machine-learning (ML) techniques have drawn an ever-increasing focus as they enable high-throughput screening and multiscale prediction of material properties. Especially, ML force fields (FFs) of quantum mechanical accuracy are expected to play a central role for the purpose. The construction of ML-FFs for polymers is, however, still in its infancy due to the formidable configurational space of its composing atoms. Here, we demonstrate the effective development of ML-FFs using kernel functions and a Gaussian process for an organic polymer, polytetrafluoroethylene (PTFE), with a data set acquired by first-principles calculations and ab initio molecular dynamics (AIMD) simulations. Even though the training data set is sampled only with short PTFE chains, structures of longer chains optimized by our ML-FF show an excellent consistency with density functional theory calculations. Furthermore, when integrated with molecular dynamics simulations, the ML-FF successfully describes various physical properties of a PTFE bundle, such as a density, melting temperature, coefficient of thermal expansion, and Young's modulus.

Using first-principles calculations we developed, for the first time, atomistic-level kinetics model to identify a key descriptor controlling electrochemical behaviors of various rare-earth ions solvated in molten salt electrolyte depositing on a solid electrode. We identified that the thermodynamic adsorption energies of rare-earth elements in the metallic electrode have a universal relation with exchange current densities. Our studies can be very useful guide to separate high-level radioactive nuclear materials and industrially valuable rare-earth materials, which can substantially relieve the environmental protection issues in nuclear waste disposal.

Conventionally neglected mechanism of reversible redox reactions by oxygen ions in lithium-nickel oxide materials (LNO; Li2xNi2-2xO2, 0 O Li configuration. They enable an active oxygen redox reaction involving peroxo (O22−) and superoxo (O2−) ions, shown to dramatically increase the energy density of the LNO cathode. Using Monte Carlo simulations, we identify the proportional information to find the Li O Li configurations around the synthetic temperature of LNO materials. Our results indicate that the cation-disorder is a driving force for the oxygen redox via formation of the specific bondings. On the basis of our study, it is expected to provide useful guidelines for the design of Li-ion batteries with high energy densities beyond conventional ones.

Background Fast growing cancer cells require greater amounts of ATP than normal cells. Although glycolysis was suggested as a source of anabolic metabolism based on lactate production, the main source of ATP to support cancer cell metabolism remains unidentified. Methods We have proposed that the oxoglutarate carrier SLC25A11 is important for ATP production in cancer by NADH transportation from the cytosol to mitochondria as a malate. We have examined not only changes of ATP and NADH but also changes of metabolites after SLC25A11 knock down in cancer cells. Findings The mitochondrial electron transport chain was functionally active in cancer cells. The cytosolic to mitochondrial NADH ratio was higher in non-small cell lung cancer (NSCLC) and melanoma cells than in normal cells. This was consistent with higher levels of the oxoglutarate carrier SLC25A11. Blocking malate transport by knockdown of SLC25A11 significantly impaired ATP production and inhibited the growth of cancer cells, which was not observed in normal cells. In in vivo experiments, heterozygote of SLC25A11 knock out mice suppressed KRASLA2 lung tumor formation by cross breeding. Interpretation Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production. Therefore blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production. Fund The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to SYK (NRF-2017R1A2B2003428).

Controllable synthesis of graphene-coated metal nanoparticles (NPs) presents a big challenge because the shell thickness plays a key role in activity of these catalysts. Herein, we use silica as a radical sieve to grow graphene over cobalt NPs via chemical vapor deposition. As-prepared single-layer graphene-coated cobalt NPs with and without N doping (Co@N-SG and Co@SG) exhibit noticeable oxygen evolution reaction (OER) activity of 316 and 334 mV, respectively at a current density of 10 mA cm-2. Furthermore, a magnet-assisted binder-free Co@N-SG electrode illustrates much improved OER activity and stability over conventional binder-assisted counterparts, suggesting this as an effective way to overcome the recognized issues of high electron transfer resistance and poor adhesion of binder-based electrodes in practical applications. Interestingly, the graphene shell possesses varying defects and major OER active sites are found around the defects in the shell. On the other hand, separately isolated Co@SG with a defect-free shell, despite exhibiting a slightly lower initial activity, illustrates a much-improved durable OER performance. The underlying Co affects the electron density of the graphene shell through dipole interaction and the electron density is optimized for adsorption of reaction intermediates, hence accelerating OER performance. This work will provide new clues to design efficient and durable electrocatalysts with further enhanced OER performance.

Design of highly active and stable electrocatalyst is a major objective in a fuel cell. The special situation imposed to the electrocatalyst such as one of the most sluggish catalysis of oxygen reduction reaction, inherent structural instability of dispersed nanoparticle, harsh electrochemical conditions of electric potential and nonzero pH aqueous solution requires unique attention in the design. Considering that various attempts have been made for the purpose, high-speed but rigorous formalisms to evaluate the performance of candidates are crucial. This review article briefly introduces recently developed first-principles computational methodologies mainly applied to catalytic activity and electrochemical stability of electrocatalysts in proton exchange membrane fuel cells. Innovative design principles deduced from the outcomes are clearly discussed.

Lithium-sulfur batteries have theoretical specific energy higher than state-of-the-art lithium-ion batteries. However, from a practical perspective, these batteries exhibit poor cycle life and low energy content owing to the polysulfides shuttling during cycling. To tackle these issues, researchers proposed the use of redox-inactive protective layers between the sulfur-containing cathode and lithium metal anode. However, these interlayers provide additional weight to the cell, thus, decreasing the practical specific energy. Here, we report the development and testing of redox-active interlayers consisting of sulfur-impregnated polar ordered mesoporous silica. Differently from redox-inactive interlayers, these redox-active interlayers enable the electrochemical reactivation of the soluble polysulfides, protect the lithium metal electrode from detrimental reactions via silica-polysulfide polar-polar interactions and increase the cell capacity. Indeed, when tested in a non-aqueous Li-S coin cell configuration, the use of the interlayer enables an initial discharge capacity of about 8.5 mAh cm−2 (for a total sulfur mass loading of 10 mg cm−2) and a discharge capacity retention of about 64 % after 700 cycles at 335 mA g−1 and 25 °C.

Recent findings indicate that (a) mitochondria in proliferating cancer cells are functional, (b) cancer cells use more oxygen than normal cells for oxidative phosphorylation, and (c) cancer cells critically rely on cytosolic NADH transported into mitochondria via the malate-aspartate shuttle (MAS) for ATP production. In a spontaneous lung cancer model, tumor growth was reduced by 50% in heterozygous oxoglutarate carrier (OGC) knock-out mice compared with wild-type counterparts. To determine the mechanism through which OGC promotes tumor growth, the effects of the OGC inhibitor N-phenylmaleimide (NPM) on mitochondrial activity, oxygen consumption, and ATP production were evaluated in melanoma cell lines. NPM suppressed oxygen consumption and decreased ATP production in melanoma cells in a dose-dependent manner. NPM also reduced the proliferation of melanoma cells. To test the effects of NPM on tumor growth and metastasis in vivo, NPM was administered in a human melanoma xenograft model. NPM reduced tumor growth by approximately 50% and reduced melanoma invasion by 70% at a dose of 20 mg/kg. Therefore, blocking OGC activity may be a useful approach for cancer therapy.

The greatest challenge in cancer therapy is posed by drug-resistant recurrence following treatment. Anticancer chemotherapy is largely focused on targeting the rapid proliferation and biosynthesis of cancer cells. This strategy has the potential to trigger autophagy, enabling cancer cell survival through the recycling of molecules and energy essential for biosynthesis, leading to drug resistance. Autophagy recycling contributes amino acids and ATP to restore mTOR complex 1 (mTORC1) activity, which leads to cell survival. However, autophagy with mTORC1 activation can be stalled by reducing the ATP level. We have previously shown that cytosolic NADH production supported by aldehyde dehydrogenase (ALDH) is critical for supplying ATP through oxidative phosphorylation (OxPhos) in cancer cell mitochondria. Inhibitors of the mitochondrial complex I of the OxPhos electron transfer chain and ALDH significantly reduce the ATP level selectively in cancer cells, terminating autophagy triggered by anticancer drug treatment. With the aim of overcoming drug resistance, we investigated combining the inhibition of mitochondrial complex I, using phenformin, and ALDH, using gossypol, with anticancer drug treatment. Here, we show that OxPhos targeting combined with anticancer drugs acts synergistically to enhance the anticancer effect in mouse xenograft models of various cancers, which suggests a potential therapeutic approach for drug-resistant cancer.

More than 50% of human cancers harbor TP53 mutations and increased expression of Mouse double minute 2 homolog (MDM2), which contribute to cancer progression and drug resistance. Renal cell carcinoma (RCC) has an unusually high incidence of wild-type p53, with a mutation rate of less than 4%. MDM2 is master regulator of apoptosis in cancer cells, which is triggered through proteasomal degradation of wild-type p53. Recently, we found that p53 protein levels in RCC are regulated by autophagic degradation. Transglutaminase 2 (TGase 2) was responsible for p53 degradation through this pathway. Knocking down TGase 2 increased p53-mediated apoptosis in RCC. Therefore, we asked whether depleting p53 from RCC cells occurs via MDM2-mediated proteasomal degradation or via TGase 2-mediated autophagic degradation. In vitro gene knockdown experiments revealed that stability of p53 in RCC was inversely related to levels of both MDM2 and TGase 2 protein. Therefore, we examined the therapeutic efficacy of inhibitors of TGase 2 and MDM2 in an in vivo model of RCC. The results showed that inhibiting TGase 2 but not MDM2 had efficient anticancer effects.

Lung adenocarcinoma cells express high levels of ALDH1L1, an enzyme of the one-carbon pathway that catalyzes the conversion of 10-formyltetrahydrofolate into tetrahydrofolate and NAD(P)H. In this study, we evaluated the potential of ALDH1L1 as a therapeutic target by deleting the Aldh1l1 gene in KrasLA2 mice, a model of spontaneous non-small cell lung cancer (NSCLC). Reporter assays revealed KRAS-mediated upregulation of the ALDH1L1 promoter in human NSCLC cells. Aldh1l1&minus, /&minus, mice exhibited a normal phenotype, with a 10% decrease in Kras-driven lung tumorigenesis. By contrast, the inhibition of oxidative phosphorylation inhibition using phenformin in Aldh1l1&minus, KrasLA2 mice dramatically decreased the number of tumor nodules and tumor area by up to 50%. Furthermore, combined treatment with pan-ALDH inhibitor and phenformin showed a decreased number and area of lung tumors by 70% in the KrasLA2 lung cancer model. Consistent with this, previous work showed that the combination of ALDH1L1 knockdown and phenformin treatment decreased ATP production by as much as 70% in NSCLS cell lines. Taken together, these results suggest that the combined inhibition of ALDH activity and oxidative phosphorylation represents a promising therapeutic strategy for NSCLC.

Safe control and removal of radioactive iodine gases (I-129 and I-131) leaking from the accidents in chemical factories or nuclear industries are of importance because of their critical damage to the biosphere. We study the adsorptive removal of the off-gaseous iodine using transition metals of group 10 and group 11 under humid conditions. First-principles calculations enable to capture key adsorption natures of iodine and water molecules on the adsorbent surfaces. The underlying mechanism is analyzed by thermodynamic free energies, electronic structures, and surface work function changes. Our results unveil why silver metal shows notably outstanding efficiency for the iodine removal. We propose an innovative and insightful map to guide sorting out the best metal adsorbents and impregnants for dramatic improvement of the adsorptive removal of the radioactive iodine gas. Our study is useful for preventing critical risks from chemical and nuclear accidents.

Hydrogen gas has been regarded as a promising fuel for securing energy and environmental sustainability of our society. Accordingly, efficient and large scale production of hydrogen is central issue due to high activation barrier unless costly transition metal catalysts are used. Here, we screen optimum catalysts toward hydrogen evolution among cheap pyrites using first-principles density functional theory calculations and rigorous thermodynamic approach. A key thermodynamic state variable accurately describes the catalytic activity, of which the mechanism is unveiled by a universal linear correlation between kinetic exchange current density in hydrogen evolution reaction and thermodynamic adsorption energy of hydrogen atom over various pyrites. On the basis of the results, we propose a design principle for substantial tuning the catalytic performance.

The solid electrolyte interphase (SEI) of Li-ion batteries (LIBs) has been extensively studied, with most research focused on the anode, because of its significant impact on the prolonged cycle life, initial capacity loss, and safety issues. Using first-principles density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations with the Hubbard correction, we examine the thermodynamic structure prediction and electrochemical stability of a spinel LiMn2O4 cathode interfaced with a carbonate electrolyte. The electronic energy levels of frontier orbitals of the electrolyte and the work function of the cathode offer clear characterization of the interfacial reactions. Our results based on both DFT calculations and AIMD simulations propose that the proton transfer mechanism at the hybrid interface is essential for initiating the SEI layer formation on the LiMn2O4 surface. Our results can be useful for identifying design concepts in the development of stable and high capacity LIBs with optimized electrodes and high-performance electrolytes.

Using first principles calculations we unveil fundamental mechanism of hydrolysis reactions of two hazardous chemicals PCl3 and POCl3 with explicit molecular water clusters nearby. It is found that the water molecules play a key role as a catalyst significantly lowing activation barrier of the hydrolysis via transferring its protons to reaction intermediates. Interestingly, torsional angle of the molecular complex at transition state is identified as a vital descriptor on the reaction rate. Analysis of charge distribution over the complex further reinforces the finding with atomic level correlation between the torsional angle and variation of the orbital hybridization state of phosphorus (P) in the complex. Electronic charge separation (or polarization) enhances thermodynamic stability of the activated complex and reduces the activation energy through hydrogen bonding network with water molecules nearby. Calculated potential energy surfaces (PES) for the hydrolysis of PCl3 and POCl3 depict their two contrastingly different profiles of double- and triple-depth wells, respectively. It is ascribed to the unique double-bonding O=P in the POCl3. Our results on the activation free energy show well agreements with previous experimental data within 7kcalmol-1 deviation.

The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonenal, which was converted to fatty acids with NADH production by ALDH3A1, resulting in further fatty acid oxidation. Inhibition of ALDH3A1 by knock down using siRNA of ALDH3A1 resulted in significantly reduced ATP production by cancer cells, leading to apoptosis. Oxidative phosphorylation by mitochondria in gastric cancer cells was driven by NADH supplied via fatty acid oxidation. Therefore, blockade of ALDH3A1 together with mitochondrial complex I using gossypol and phenformin led to significant therapeutic effects in a preclinical gastric cancer model.

In the Cancers paper, we observed the increase ALDH1L1 protein expression following oncogenesis, as well as a therapeutic effect, by deleting the Aldh1l1 gene in KrasLA2 mice, a model of spontaneous non-small cell lung cancer (NSCLC) [...]

Composition modulation by Ar bombardment on the Co0.5Cu0.5 alloy and the CoAl B2 phase was investigated on atomic scale by molecular dynamics simulation. The Ar bombardment on alloys at 300 K revealed that this bombardment induces a surface composition modulation in the layer-by-layer mode. In both the Co0.5Cu0.5 alloy and the CoAl B2 phase, the element of higher-sputtering yield is accumulated on the top surface layer, whereas it is depleted in lower layers, which is puzzling in the framework the conventional sputtering theory. A phenomenological kinetic model derived from the MD simulation results considering both the rearrangement and the sputtering of the substrate atoms successfully demonstrated that the rearrangement of the substrate atoms plays a significant role in the observed composition modulation.

Correction for ‘High performance binder-free Fe–Ni hydroxides on nickel foam prepared in piranha solution for the oxygen evolution reaction’ by Cheol-Hwan Shin et al., Sustainable Energy Fuels, 2020, 4, 6311–6320, DOI: 10.1039/D0SE01253J.

Using first principles density functional theory (DFT) calculations we obtain thermodynamic and kinetic properties of U in an electrorefining process for spent nuclear fuels using a LiCl-KCl eutectic molten salt and Mo as a cathode. The thermodynamic stability of electrodeposited U from the molten salt onto the Mo(110) surface electrode is evaluated by activity coefficients as function of surface coverages of U and Cl. Additionally, ab-initio molecular dynamic simulations combined with the Stokes-Einstein-Sutherland relation enables us to calculate the viscosity of the LiCl-KCl eutectic molten salt. Our results well agree with previously reported experimental data endorsing the credibility. Based on our atomic-level mechanical understanding we propose that an accurate computational model system incorporating the electrochemical conditions of the electrorefining process essential for the purpose of establishing thermodynamic and kinetic database of U, otherwise critical deviations are inevitable. More interestingly, the effect of coadsorption of Cl with U on the Mo(110) surface plays a key role in stabilizing electrodeposited U on the cathode. Our approach can be useful for validating published experimental database and for identifying key factors guiding a rational design of highly efficient electrorefining system for spent nuclear fuels, and thus reducing high-level radioactive nuclear wastes.

We study removal of gas-phase organic methyl iodide (CH3I) from an ambient environment via adsorption onto triethylenediamine (TEDA) impregnated activated carbon (AC). First principles density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulations were extensively utilized to understand the underlying mechanism for the chemical reaction of CH3I on the surface. Our results suggest that the adsorption energy of CH3I shows substantial heterogeneity depending on the adsorption site, porosity of the AC, and humidity. It is observed that the CH3I dissociative chemisorption is largely influenced by the adsorption site and porosity. Most importantly, it is clearly shown through free energy diagrams that the impregnated TEDA not only reduces the dissociation activation barrier of CH3I but also attracts H2O molecules relieving the AC surface from poisoning by humidity, and also enhances the removal efficiency of CH3I through the chemical dissociation reaction. Our computational study can help to open new routes to design highly efficient materials for removing environmentally and biologically hazardous materials, for example radioactive iodine gas emitted following accidents at a nuclear power plant.

Simple Summary We found a conserved pathway for the energy supply in cancer. The present study revealed that glucose is not a major source of ATP production, whereas fatty acid is a major source of electrons for ATP production through fatty acid oxidation (FAO) and oxidative phosphorylation (OxPhos) in cancer cells. NADH is mainly recruited from FAO, which is used for ATP synthesis via OxPhos with electron transfer complexes in cancer cells while ATP is synthesized from NADH produced in the TCA cycle in the normal cells. Therefore, a calorie-balanced low-fat diet showed 3-fold reduction of tumor formation, whereas a high-fat diet caused a 2-fold increase of tumor to compare to the control in a human pancreatic ductal adenocarcinoma xenograft and a homograft KC models. Abstract Glycolysis is known as the main pathway for ATP production in cancer cells. However, in cancer cells, glucose deprivation for 24 h does not reduce ATP levels, whereas it does suppress lactate production. In this study, metabolic pathways were blocked to identify the main pathway of ATP production in pancreatic ductal adenocarcinoma (PDAC). Blocking fatty acid oxidation (FAO) decreased ATP production by 40% in cancer cells with no effect on normal cells. The effects of calorie balanced high- or low-fat diets were tested to determine whether cancer growth is modulated by fatty acids instead of calories. A low-fat diet caused a 70% decrease in pancreatic preneoplastic lesions compared with the control, whereas a high-fat diet caused a two-fold increase in preneoplastic lesions accompanied with increase of ATP production in the Kras (G12D)/Pdx1-cre PDAC model. The present results suggest that ATP production in cancer cells is dependent on FAO rather than on glycolysis, which can be a therapeutic approach by targeting cancer energy metabolism.

Angiogenesis and the expression of vascular endothelial growth factor (VEGF) are increased in renal cell carcinoma (RCC). Transglutaminase 2 (TGase 2), which promotes angiogenesis in endothelial cells during wound healing, is upregulated in RCC. Tumor angiogenesis involves three domains: cancer cells, the extracellular matrix, and endothelial cells. TGase 2 stabilizes VEGF in the extracellular matrix and promotes VEGFR-2 nuclear translocation in endothelial cells. However, the role of TGase 2 in angiogenesis in the cancer cell domain remains unclear. Hypoxia-inducible factor (HIF)-1α-mediated VEGF production underlies the induction of angiogenesis in cancer cells. In this study, we show that p53 downregulated HIF-1α in RCC, and p53 overexpression decreased VEGF production. Increased TGase 2 promoted angiogenesis by inducing p53 degradation, leading to the activation of HIF-1α. The interaction of HIF-1α and p53 with the cofactor p300 is required for stable transcriptional activation. We found that TGase 2-mediated p53 depletion increased the availability of p300 for HIF-1α-p300 binding. A preclinical xenograft model suggested that TGase 2 inhibition can reverse angiogenesis in RCC.

Atomic-level understanding of hybrid interface reactions for metal and oxide plays an important role in innovative design of multifunctional materials. We apply first-principles calculations to thin layers of metallic Ni and oxide α-Al2O3 (Ni/α-Al2O3) and unveil reaction mechanism under extreme thermodynamic conditions (T > 2500 K and pressure P ∼ 40 GPa). In such thermally shocked state, we track interface reaction scenario by calculations of thermodynamically feasible structures and energy convex hull: (i) chemical-bond break of α-Al2O3 enabling fast diffusion of O into Ni atomic layers, (ii) formation of NiO, (iii) formation of intermetallic compounds NixAl1-x and followed by (iv) evolution of O2 gas. The NiO is formed locally at around the interface for short time period at the beginning of the interface reactions. Intermetallic compounds NixAl1−x are thermodynamically unstable against the decomposition into Al2O3 and Ni. It is also elucidated that abrupt mechanical shock to the interface by such a high pressure adiabatically raise interface temperature extremely high, in which mixtures of NixAl1−x are stabilized by releasing O2(g). We neatly summarize the interface reactions using an Ellingham diagram.

Anticancer drug resistance is a major challenge of cancer therapy. We found that irinotecan-resistant NSCLC cells showed increased mitochondrial oxidative phosphorylation compared to the drug sensitive NSCLC cells. Previously, we found that combined inhibition of aldehyde dehydrogenase using gossypol, and mitochondrial complex I using phenformin, effectively reduced oxidative phosphorylation in NSCLC. Here, we showed that targeting oxidative phosphorylation with gossypol and phenformin abrogated irinotecan resistance in NSCLC. Furthermore, irinotecan treatment by blocking oxidative phosphorylation induced synergistic anti-cancer effect in NSCLC. The pre-clinical xenograft model of human NSCLC also demonstrated a therapeutic response to the dual targeting treatment. Therefore, this combination of gossypol and phenformin increases irinotecan sensitivity as well as preventing irinotecan resistance.

In general, expression of transglutaminase 2 (TGase 2) is upregulated in renal cell carcinoma (RCC), resulting in p53 instability. Previous studies show that TGase 2 binds to p53 and transports it to the autophagosome. Knockdown or inhibition of TGase 2 in RCC induces p53-mediated apoptosis. Here, we screened a chemical library for TGase 2 inhibitors and identified streptonigrin as a potential therapeutic compound for RCC. Surface plasmon resonance and mass spectroscopy were used to measure streptonigrin binding to TGase 2. Mass spectrometry analysis revealed that streptonigrin binds to the N-terminus of TGase 2 (amino acids 95&ndash, 116), which is associated with inhibition of TGase 2 activity in vitro and with p53 stabilization in RCC. The anti-cancer effects of streptonigrin on RCC cell lines were demonstrated in cell proliferation and cell death assays. In addition, a single dose of streptonigrin (0.2 mg/kg) showed marked anti-tumor effects in a preclinical RCC model by stabilizing p53. Inhibition of TGase 2 using streptonigrin increased p53 stability, which resulted in p53-mediated apoptosis of RCC. Thus, targeting TGase 2 may be a new therapeutic approach to RCC.

Understanding of the fundamental mechanisms causing significant enhancement of Li-ionic conductivity by Al 3+ doping to a solid LiGe 2 (PO 4 ) 3 (LGP) electrolyte is pursued using first principles density functional theory (DFT) calculations combined with experimental measurements. Our results indicate that partial substitution Al 3+ for Ge 4+ in LiGe 2 (PO 4 ) 3 (LGP) with aliovalent (Li 1+x Al x Ge 2−x (PO 4 ) 3 , LAGP) improves the Li-ionic conductivity about four-orders of the magnitude. To unveil the atomic origin we calculate plausible diffusion paths of Li in LGP and LAGP materials using DFT calculations and a nudged elastic band method, and discover that LAGP had additional transport paths for Li with activation barriers as low as only 34% of the LGP. Notably, these new atomic channels manifest subtle electrostatic environments facilitating cooperative motions of at least two Li atoms. Ab-initio molecular dynamics predict Li-ionic conductivity for the LAGP system, which is amazingly agreed experimental measurement on in-house made samples. Consequently, we suggest that the excess amounts of Li caused by the aliovalent Al 3+ doping to LGP lead to not only enhancing Li concentration but also opening new conducting paths with substantially decreases activation energies and thus high ionic conductivity of LAGP solid-state electrolyte.