Convolutional neural networks can detect orthostatic hypotension in Parkinson's disease using resting-state functional near-infrared spectroscopy data.

Neurological disorders such as Parkinson's disease (PD) often adversely affect the vascular system, leading to alterations in blood flow patterns. Functional near-infrared spectroscopy (fNIRS) is used to monitor hemodynamic changes via signal measurement. This study investigated the potential of using resting-state fNIRS data through a convolutional neural network (CNN) to evaluate PD with orthostatic hypotension. The CNN demonstrated significant efficacy in analyzing fNIRS data, and it outperformed the other machine learning methods. The results indicate that judicious input data selection can enhance accuracy by over 85%, while including the correlation matrix as an input further improves the accuracy to more than 90%. This study underscores the promising role of CNN-based fNIRS data analysis in the diagnosis and management of the PD. This approach enhances diagnostic accuracy, particularly in resting-state conditions, and can reduce the discomfort and risks associated with current diagnostic methods, such as the head-up tilt test.

Critical role of slags in pitting corrosion of additively manufactured stainless steel in simulated seawater.

Pitting corrosion in seawater is one of the most difficult forms of corrosion to identify and control. A workhorse material for marine applications, 316L stainless steel (316L SS) is known to balance resistance to pitting with good mechanical properties. The advent of additive manufacturing (AM), particularly laser powder bed fusion (LPBF), has prompted numerous microstructural and mechanical investigations of LPBF 316L SS; however, the origins of pitting corrosion on as-built surfaces is unknown, despite their utmost importance for certification of LPBF 316L SS prior to fielding. Here, we show that Mn-rich silicate slags are responsible for pitting of the as-built LPBF material in sodium chloride due to their introduction of deleterious defects such as cracks or surface oxide heterogeneities. In addition, we explain how slags are formed in the liquid metal and deposited at the as-built surfaces using high-fidelity melt pool simulations. Our work uncovers how LPBF changes surface oxides due to rapid solidification and high-temperature oxidation, leading to fundamentally different pitting corrosion mechanisms.

Density Functional Theory Study of Synergistic Gas Sensing Using an Electrically Conductive Mixed Ligand Two-Dimensional Metal-Organic Framework.

Two-dimensional conductive metal-organic frameworks (2D-cMOFs) have been adopted in electrochemical sensing applications owing to their superior electrical conductivity and large surface area. Here, we performed a density functional theory (DFT) analysis to study the synergistic impact of introducing a secondary organic ligand to the 2D-cMOF system. In this study, cobalt-hexaiminobenzene (Co-HIB) and cobalt-2,3,6,7,10,11-hexaiminotriphenylene (Co-HITP) were combined to form a mixed ligand MOF named, Co-HIB-HITP. A DFT-level comparative study was designed to access stability, synergistic gas adsorption capability, and gas adsorption mechanism, important factors in sensing material development. A potential energy surface calculation predicted the structural stability of Co-HIB-HITP at larger interlayer displacements around 3.6-4.2 Å regions along the ab-plane than its unmixed states, Co-HIB and Co-HITP, indicating the tunability of the stacking mode using the mixed ligand system. Furthermore, the adsorption capabilities toward toxic gases, NH3, H2S, NO, and NO2, were investigated, and Co-HIB-HITP revealed superiority over unmixed 2D-cMOFs in H2S and NH3 gas adsorption energies by showing 158 and 170% improvement, respectively. Finally, an electron charge density analysis revealed Co-HIB-HITP's unique stacking mode and Co-metal density as contributing factors to its gas-selective synergy effect. The AB stacked layers and an intermediate metal density (5.25%) significantly improved the electrostatic interactions with H2S and NH3 by inducing a change in the chemical environment of the gas binding sites. This work proposes the dual-ligand 2D-cMOF as the promising design strategy for the next-generation sensing material.

Flexible machine-learning interatomic potential for simulating structural disordering behavior of Li7La3Zr2O12 solid electrolytes.

Batteries based on solid-state electrolytes, including Li7La3Zr2O12 (LLZO), promise improved safety and increased energy density; however, atomic disorder at grain boundaries and phase boundaries can severely deteriorate their performance. Machine-learning (ML) interatomic potentials offer a uniquely compelling solution for simulating chemical processes, rare events, and phase transitions associated with these complex interfaces by mixing high scalability with quantum-level accuracy, provided that they can be trained to properly address atomic disorder. To this end, we report the construction and validation of an ML potential that is specifically designed to simulate crystalline, disordered, and amorphous LLZO systems across a wide range of conditions. The ML model is based on a neural network algorithm and is trained using ab initio data. Performance tests prove that the developed ML potential can predict accurate structural and vibrational characteristics, elastic properties, and Li diffusivity of LLZO comparable to ab initio simulations. As a demonstration of its applicability to larger systems, we show that the potential can correctly capture grain boundary effects on diffusivity, as well as the thermal transition behavior of LLZO. These examples show that the ML potential enables simulations of transitions between well-defined and disordered structures with quantum-level accuracy at speeds thousands of times faster than ab initio methods.

Heteroatom-Doped Graphenes as Actively Interacting 2D Encapsulation Media for Mg-Based Hydrogen Storage.

Nanoencapsulation using graphene derivatives enables the facile fabrication of two-dimensional (2D) nanocomposites with unique microstructures and has been generally applied to many fields of energy materials. Particularly, metal hydrides such as MgH2 encapsulated by graphene derivatives have emerged as a promising hybrid material for overcoming the disadvantageous properties of Mg-based hydrogen storage. Although the behavior of the graphene-Mg nanoencapsulation interface has been studied for many composite materials, the direct modification of graphene with nonmetal foreign elements for changing the interfacial behavior has been limitedly reported. In this regard, using B-doped graphene and N-doped graphene as nanoencapsulation media for tuning the interfacial behavior of graphene derivative-Mg nanoparticles, we present altered hydrogen storage kinetics of heteroatom-doped (B and N) graphene-Mg composites. The effect of heteroatom doping is studied in terms of bonding configurations and heteroatom doping concentrations. The enhancement in hydrogen uptake was observed for all of the heteroatom-doped graphene-Mg nanocomposites. On the other hand, a few samples exhibit significantly low activation energy at the early stage of desorption, which can be related to the facilitated nucleus formation. Density functional theory calculation indicates that B-doping and N-doping accelerate hydrogen absorption kinetics in different ways, aiding charge transfer and inducing surface deformation of Mg nanoparticles, respectively. Their effects can be augmented in the presence of structural defects on graphene, such as vacancies, pores, or graphene edges. These results demonstrate that hydrogen storage kinetics of Mg-based systems can be altered by utilizing heteroatom-doped graphene oxide derivatives as 2D nanoencapsulation media, suggesting that the addition of a nonmetal doping element can also be applied to Mg-based hydrogen storage by modifying the nanoencapsulation interface without forming Mg alloy phases.

Understanding Hydrogenation Chemistry at MgB2 Reactive Edges from Ab Initio Molecular Dynamics.

Solid-state hydrogen storage materials often operate via transient, multistep chemical reactions at complex interfaces that are difficult to capture. Here, we use direct ab initio molecular dynamics simulations at accelerated temperatures and hydrogen pressures to probe the hydrogenation chemistry of the candidate material MgB2 without a priori assumption of reaction pathways. Focusing on highly reactive (101̅0) edge planes where initial hydrogen attack is likely to occur, we track mechanistic steps toward the formation of hydrogen-saturated BH4- units and key chemical intermediates, involving H2 dissociation, generation of functionalities and molecular complexes containing BH2 and BH3 motifs, and B-B bond breaking. The genesis of higher-order boron clustering is also observed. Different charge states and chemical environments at the B-rich and Mg-rich edge planes are found to produce different chemical pathways and preferred speciation, with implications for overall hydrogenation kinetics. The reaction processes rely on B-H bond polarization and fluctuations between ionic and covalent character, which are critically enabled by the presence of Mg2+ cations in the nearby interphase region. Our results provide guidance for devising kinetic improvement strategies for MgB2-based hydrogen storage materials, while also providing a template for exploring chemical pathways in other solid-state energy storage reactions.

Spontaneous dynamical disordering of borophenes in MgB2 and related metal borides.

Layered boron compounds have attracted significant interest in applications from energy storage to electronic materials to device applications, owing in part to a diversity of surface properties tied to specific arrangements of boron atoms. Here we report the energy landscape for surface atomic configurations of MgB2 by combining first-principles calculations, global optimization, material synthesis and characterization. We demonstrate that contrary to previous assumptions, multiple disordered reconstructions are thermodynamically preferred and kinetically accessible within exposed B surfaces in MgB2 and other layered metal diborides at low boron chemical potentials. Such a dynamic environment and intrinsic disordering of the B surface atoms present new opportunities to realize a diverse set of 2D boron structures. We validated the predicted surface disorder by characterizing exfoliated boron-terminated MgB2 nanosheets. We further discuss application-relevant implications, with a particular view towards understanding the impact of boron surface heterogeneity on hydrogen storage performance.

Multichannel near-infrared spectroscopy brain imaging system for small animals in mobile conditions.

Significance: We propose a customized animal-specific head cap and an near-infrared spectroscopy (NIRS) system to obtain NIRS signals in mobile small animals. NIRS studies in mobile small animals provide a feasible solution for comprehensive brain function studies. Aim: We aim to develop and validate a multichannel NIRS system capable of performing functional brain imaging along with a closed-box stimulation kit for small animals in mobile conditions. Approach: The customized NIRS system uses light-weight long optical fibers, along with a customized light-weight head cap to securely attach the optical fibers to the mouse. A customized stimulation box was designed to perform various stimuli in a controlled environment. The system performance was tested in a visual stimulation task on eight anesthetized mice and eight freely moving mice. Results: Following the visual stimulation task, we observed a significant stimulation-related oxyhemoglobin (HbO) increase in the visual cortex of freely moving mice during the task. In contrast, HbO concentration did not change significantly in the visual cortex of anesthetized mice. Conclusions: We demonstrate the feasibility of a wearable, multichannel NIRS system for small animals in a less confined experimental design.

Regional analysis of cerebral hemodynamic changes during the head-up tilt test in Parkinson's disease patients with orthostatic intolerance.

Significance: Cerebral oxygenation changes in the superior, middle, and medial gyri were used to elucidate spatial impairments of autonomic hemodynamic recovery during the head-up tilt table test (HUTT) in Parkinson's disease (PD) patients with orthostatic intolerance (OI) symptoms. Aim: To analyze dynamic oxygenation changes during the HUTT and classify PD patients with OI symptoms using clinical and oxygenation features. Approach: Thirty-nine PD patients with OI symptoms [10: orthostatic hypotension (PD-OH); 29: normal HUTT results (PD-NOR)] and seven healthy controls (HCs) were recruited. Prefrontal oxyhemoglobin (HbO) changes during the HUTT were reconstructed with diffuse optical tomography and segmented using the automated anatomical labeling system. Decision trees were used for classification. Results: HCs and PD-NOR patients with positive rates of HbO change (PD-POS) showed the greatest HbO recovery in the superior frontal gyrus (SFG) during tilt. PD-OH and PD-NOR patients with negative rates of HbO change (PD-NEG) showed asymmetric reoxygenation. The classification accuracy was 89.4% for PD-POS versus PD-NEG, 71% for PD-NOR versus PD-OH, and 55.8% for PD-POS versus PD-NEG versus PD-OH. The oxygenation features were more discriminative than the clinical features. Conclusions: PD-OH showed decreased right SFG function, which may be associated with impaired compensatory autonomic responses to orthostatic stress.

Fully Exploited Oxygen Redox Reaction by the Inter-Diffused Cations in Co-Free Li-Rich Materials for High Performance Li-Ion Batteries.

To meet the growing demand for global electrical energy storage, high-energy-density electrode materials are required for Li-ion batteries. To overcome the limit of the theoretical energy density in conventional electrode materials based solely on the transition metal redox reaction, the oxygen redox reaction in electrode materials has become an essential component because it can further increase the energy density by providing additional available electrons. However, the increase in the contribution of the oxygen redox reaction in a material is still limited due to the lack of understanding its controlled parameters. Here, it is first proposed that Li-transition metals (TMs) inter-diffusion between the phases in Li-rich materials can be a key parameter for controlling the oxygen redox reaction in Li-rich materials. The resulting Li-rich materials can achieve fully exploited oxygen redox reaction and thereby can deliver the highest reversible capacity leading to the highest energy density, ≈1100 Wh kg-1 among Co-free Li-rich materials. The strategy of controlling Li/transition metals (TMs) inter-diffusion between the phases in Li-rich materials will provide feasible way for further achieving high-energy-density electrode materials via enhancing the oxygen redox reaction for high-performance Li-ion batteries.

Anti-inflammatory potential of Patrineolignan B isolated from Patrinia scabra in LPS-stimulated macrophages via inhibition of NF-κB, AP-1, and JAK/STAT pathways.

Patrineolignan B (PB), a lignan compound isolated from the radix and rhizomes of Patrinia scabra, was previously reported to possess a strong tumor-specific cytotoxic activity and beneficial effects on nitric oxide (NO) levels in macrophages induced by lipopolysaccharide (LPS). In this study, we assessed the effects of PB on LPS-induced inflammation in RAW 264.7 cells and clarified its molecular mechanisms. PB reversed LPS-induced increase in NO levels and prostaglandin E2 (PGE2) production, as well as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and mRNA levels in macrophages. Besides, PB prevented the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in a concentration-dependent manner. The regulatory effects of PB on LPS-induced inflammatory mediators and overproduction of pro-inflammatory cytokines were shown to depend partly on the suppression of nuclear factor kappa B (NF-κB)-mediated transcription and AP-1 activation regulated by a c-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK). Its anti-inflammatory activity was also mediated by regulating the phosphorylation of Janus kinase (JAK)/signal transducers and activators of transcription 1/3 (STAT1/3) signaling pathway. Taken together, our results suggest that PB exhibits anti-inflammatory potency through interfering with the NF-κB, AP-1, and JAK/STAT signaling pathway in LPS-stimulated macrophages.

Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by mitochondrial dysfunction, Lewy body formation, and loss of dopaminergic neurons. Parkin, an E3 ubiquitin ligase, is thought to inhibit PD progression by removing damaged mitochondria and suppressing the accumulation of α-synuclein and other protein aggregates. The present study describes a protein-based therapy for PD enabled by the development of a cell-permeable Parkin protein (iCP-Parkin) with enhanced solubility and optimized intracellular delivery. iCP-Parkin recovered damaged mitochondria by promoting mitophagy and mitochondrial biogenesis and suppressed toxic accumulations of α-synuclein in cells and animals. Last, iCP-Parkin prevented and reversed declines in tyrosine hydroxylase and dopamine expression concomitant with improved motor function induced by mitochondrial poisons or enforced α-synuclein expression. These results point to common, therapeutically tractable features in PD pathophysiology, and suggest that motor deficits in PD may be reversed, thus providing opportunities for therapeutic intervention after the onset of motor symptoms.

Cerebral hemodynamic monitoring of Parkinson's disease patients with orthostatic intolerance during head-up tilt test.

Significance: Monitoring of cerebral perfusion rather than blood pressure changes during a head-up tilt test (HUTT) is proposed to understand the pathophysiological effect of orthostatic intolerance (OI), including orthostatic hypotension (OH), in Parkinson's disease (PD) patients. Aim: We aim to characterize and distinguish the cerebral perfusion response to a HUTT for healthy controls (HCs) and PD patients with OI symptoms. Approach: Thirty-nine PD patients with OI symptoms [10 PD patients with OH (PD-OH) and 29 PD patients with normal HUTT results (PD-NOR)], along with seven HCs participated. A 108-channel diffuse optical tomography (DOT) system was used to reconstruct prefrontal oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT) changes during dynamic tilt (from supine to 70-deg tilt) and static tilt (remained tilted at 70 deg). Results: HCs showed rapid recovery of cerebral perfusion in the early stages of static tilt. PD-OH patients showed decreasing HbO and HbT during dynamic tilt, continuing into the static tilt period. The rate of HbO change from dynamic tilt to static tilt is the distinguishing feature between HCs and PD-OH patients. Accordingly, PD-NOR patients were subgrouped based on positive-rate and negative-rate of HbO change. PD patients with a negative rate of HbO change were more likely to report severe OI symptoms in the COMPASS questionnaire. Conclusions: Our findings showcase the usability of DOT for sensitive detection and quantification of autonomic dysfunction in PD patients with OI symptoms, even those with normal HUTT results.

Patriscabrin F from the roots of Patrinia scabra attenuates LPS-induced inflammation by downregulating NF-κB, AP-1, IRF3, and STAT1/3 activation in RAW 264.7 macrophages.

BACKGROUND: The roots of Partrinia scabra have been used as a medicinal herb in Asia. We previously reported that the inhibitory effect of patriscabrin F on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was the most potent than that of other isolated iridoids from the roots of P. scabra. PURPOSE: We investigated the anti-inflammatory activity of patriscabrin F as an active compound of P. scabra and related signaling cascade in LPS-activated macrophages. METHOD: The anti-inflammatory activities of patriscabrin F were determined according to its inhibitory effects on NO, prostaglandin E2 (PGE2), and pro-inflammatory cytokines. The molecular mechanisms were revealed by analyzing nuclear factor-κB (NF-κB), activator protein-1 (AP-1), interferon regulatory factor 3 (IRF3), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. RESULTS: Patriscabrin F inhibited the LPS-induced production of NO, PGE2, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in both bone-marrow derived macrophages (BMDMs) and RAW 264.7 macrophages. Patriscabrin F downregulated LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), TNF-α, IL-1ß, and IL-6 at the transcriptional level. Patriscabrin F suppressed LPS-induced NF-κB activation by decreasing p65 nuclear translocation, inhibitory κBα (IκBα) phosphorylation, and IκB kinase (IKK)α/ß phosphorylation. Patriscabrin F attenuated LPS-induced AP-1 activity by inhibiting c-Fos phosphorylation. Patriscabrin F suppressed the LPS-induced phosphorylation of IRF3, JAK1/JAK2, and STAT1/STAT3. CONCLUSION: Taken together, our findings suggest patriscabrin F may exhibit anti-inflammatory properties via the inhibition of NF-κB, AP-1, IRF3, and JAK-STAT activation in LPS-induced macrophages.

A Mechanistic Analysis of Phase Evolution and Hydrogen Storage Behavior in Nanocrystalline Mg(BH4)2 within Reduced Graphene Oxide.

Magnesium borohydride (Mg(BH4)2, abbreviated here MBH) has received tremendous attention as a promising onboard hydrogen storage medium due to its excellent gravimetric and volumetric hydrogen storage capacities. While the polymorphs of MBH-alpha (α), beta (ß), and gamma (γ)-have distinct properties, their synthetic homogeneity can be difficult to control, mainly due to their structural complexity and similar thermodynamic properties. Here, we describe an effective approach for obtaining pure polymorphic phases of MBH nanomaterials within a reduced graphene oxide support (abbreviated MBHg) under mild conditions (60-190 °C under mild vacuum, 2 Torr), starting from two distinct samples initially dried under Ar and vacuum. Specifically, we selectively synthesize the thermodynamically stable α phase and metastable ß phase from the γ-phase within the temperature range of 150-180 °C. The relevant underlying phase evolution mechanism is elucidated by theoretical thermodynamics and kinetic nucleation modeling. The resulting MBHg composites exhibit structural stability, resistance to oxidation, and partially reversible formation of diverse [BH4]- species during de- and rehydrogenation processes, rendering them intriguing candidates for further optimization toward hydrogen storage applications.

Chemical Constituents from the Aerial Parts of Agastache rugosa and Their Inhibitory Activities on Prostaglandin E2 Production in Lipopolysaccharide-Treated RAW 264.7 Macrophages.

A new flavone glucoside, acacetin-7-O-(3″-O-acetyl-6″-O-malonyl)-ß-d-glucopyranoside (1), two new phenolic glucosides, (3R,7R)-tuberonic acid-12-O-[6'-O-(E)-feruloyl]-ß-d-glucopyranoside (14) and salicylic acid-2-O-[6'-O-(E)-feruloyl]-ß-d-glucopyranoside (15), and two new phenylpropanoid glucosides, chavicol-1-O-(6'-O-methylmalonyl)-ß-d-glucopyranoside (17) and chavicol-1-O-(6'-O-acetyl)-ß-d-glucopyranoside(18), as well as 26 known compounds, 2-13, 16, and 19-31, were isolated from the aerial parts of Agastache rugose. The structures of the new compounds were established by spectroscopic/spectrometric methods such as HRESIMS, NMR, and ECD. The anti-inflammatory effect of the isolated compounds was evaluated by measuring their inhibitory activities on prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. New compounds 1, 15, 17, and 18 inhibited LPS-induced PGE2 production with IC50 values of 16.8 ± 0.8, 33.9 ± 4.8, 14.3 ± 2.1, and 48.8 ± 4.4 µM, respectively. Compounds 5, 7, 9-11, 13, 19, 20, 22, and 27-30 showed potent inhibitory activities with IC50 values of 1.7-8.4 µM.

Repurposing mosloflavone/5,6,7-trimethoxyflavone-resveratrol hybrids: Discovery of novel p38-α MAPK inhibitors as potent interceptors of macrophage-dependent production of proinflammatory mediators.

Herein, we address repurposing hybrids of mosloflavone or 5,6,7-trimethoxyflavone with amide analogs of resveratrol from anticancer leads to novel potent anti-inflammatory chemical entities. To unveil the potent anti-inflammatory molecules, biological evaluations were initiated in LPS-induced RAW 264.7 macrophages at 1 µM concentration. Promising compounds were further evaluated at various concentrations. Multiple proinflammatory mediators were assessed including NO, PGE2, IL-6, TNF-α and IL-1ß. Compound 5z inhibited the induced production of NO, PGE2, IL-6, TNF-α and IL-1ß at the low 1 µM concentration by 44.76, 35.71, 53.48, 29.39 and 41.02%, respectively. Compound 5z elicited IC50 values as low as 2.11 and 0.98 µM against NO and PGE2 production respectively. Compounds 5q and 5g showed potent submicromolar IC50 values of 0.31 and 0.59 µM respectively against PGE2 production. Reverse docking of compound 5z suggested p38-α MAPK, which is a key signaling molecule within the pathways controlling the transcription of proinflammatory mediators, as the molecular target. Biochemical testing confirmed these compounds as p38-α MAPK inhibitors explaining its potent inhibition of proinflammatory mediators' production. Collectively, the results presented 5z as a promising compound for further development of anti-inflammatory agents for treatment of macrophages-and/or immune mediated inflammatory diseases.

Caffeoyloxy-5,6-dihydro-4-methyl-(2H)-pyran-2-one isolated from the leaves of Olinia usambarensis attenuates LPS-induced inflammatory mediators by inactivating AP-1 and NF-κB.

We have previously reported the isolation of four compounds, caffeoyloxy-5,6-dihydro-4-methyl-(2H)-pyran-2-one (CDMP), olinioside, caffeic acid and 3-hydroxylup-12-en-28-oic acid, from the leaves of Olinia usambarensis. Here, we evaluated the inhibitory effects of these compounds on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages, and found that CDMP is the most potent of these two pro-inflammatory mediators (IC50; 12.12 µM and 10.78 µM, respectively). Consistent with these results, CDMP also down-regulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6) at the protein and mRNA levels in LPS-treated RAW 264.7 macrophages. Furthermore, CDMP suppressed LPS-induced nuclear factor κB (NF-κB) activation by decreasing p65 nuclear translocation through the phosphorylation and degradation of the inhibitory κBα (IκBα). CDMP also attenuated LPS-induced transcriptional and DNA-binding activities of activator protein 1 (AP-1) by suppressing the phosphorylation and expression of c-Fos and c-Jun. Finally, CDMP considerably suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), but did not affect the phosphorylation of p38 or extracellular signal-regulated kinase (ERK). Taken together, our data suggest that CDMP down-regulates genes encoding pro-inflammatory mediators and cytokines, such as iNOS, COX-2, TNF-α, IL-1ß, and IL-6 via NF-κB and JNK/AP-1 inactivation in LPS-induced RAW 264.7 macrophages.

Morphology-Dependent Stability of Complex Metal Hydrides and Their Intermediates Using First-Principles Calculations.

Complex light metal hydrides are promising candidates for efficient, compact solid-state hydrogen storage. (De)hydrogenation of these materials often proceeds via multiple reaction intermediates, the energetics of which determine reversibility and kinetics. At the solid-state reaction front, molecular-level chemistry eventually drives the formation of bulk product phases. Therefore, a better understanding of realistic (de)hydrogenation behavior requires considering possible reaction products along all stages of morphological evolution, from molecular to bulk crystalline. Here, we use first-principles calculations to explore the interplay between intermediate morphology and reaction pathways. Employing representative complex metal hydride systems, we investigate the relative energetics of three distinct morphological stages that can be expressed by intermediates during solid-state reactions: i) dispersed molecules; ii) clustered molecular chains; and iii) condensed-phase crystals. Our results verify that the effective reaction energy landscape strongly depends on the morphological features and associated chemical environment, offering a possible explanation for observed discrepancies between X-ray diffraction and nuclear magnetic resonance measurements. Our theoretical understanding also provides physical and chemical insight into phase nucleation kinetics upon (de)hydrogenation of complex metal hydrides.