Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models.

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

Exploring the stability and aromaticity of rare earth doped tin cluster MSn16- (M = Sc, Y, La).

Rare earth elements have high chemical reactivity, and doping them into semiconductor clusters can induce novel physicochemical properties. The study of the physicochemical mechanisms of interactions between rare earth and tin atoms will enhance our understanding of rare earth functional materials from a microscopic perspective. Hence, the structure, electronic characteristics, stability, and aromaticity of endohedral cages MSn16- (M = Sc, Y, La) have been investigated using a combination of the hybrid PBE0 functional, stochastic kicking, and artificial bee colony global search technology. By comparing the simulated results with experimental photoelectron spectra, it is determined that the most stable structure of these clusters is the Frank-Kasper polyhedron. The doping of atoms has a minimal influence on density of states of the pure tin system, except for causing a widening of the energy gap. Various methods such as ab initio molecular dynamics simulations, the spherical jellium model, adaptive natural density partitioning, localized orbital locator, and electron density difference are employed to analyze the stability of these clusters. The aromaticity of the clusters is examined using iso-chemical shielding surfaces and the gauge-including magnetically induced currents. This study demonstrates that the stability and aromaticity of a tin cage can be systematically adjusted through doping.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Making Sense of the Growth Behavior of Ultra-High Magnetic Gd2-Doped Silicon Clusters.

The growth behavior, stability, electronic and magnetic properties of the Gd2Sin- (n = 3-12) clusters are reported, which are investigated using density functional theory calculations combined with the Saunders 'Kick' and the Artificial Bee Colony algorithm. The lowest-lying structures of Gd2Sin- (n = 3-12) are all exohedral structures with two Gd atoms face-capping the Sin frameworks. Results show that the pentagonal bipyramid (PB) shape is the basic framework for the nascent growth process of the present clusters, and forming the PB structure begins with n = 5. The Gd2Si5- is the potential magic cluster due to significantly higher average binding energies and second order difference energies, which can also be further verified by localized orbital locator and adaptive natural density partitioning methods. Moreover, the localized f-electron can be observed by natural atomic orbital analysis, implying that these electrons are not affected by the pure silicon atoms and scarcely participate in bonding. Hence, the implantation of these elements into a silicon substrate could present a potential alternative strategy for designing and synthesizing rare earth magnetic silicon-based materials.

Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer.

BACKGROUND: Selenium-binding protein 1 (SELENBP1), a member of the selenium-containing protein family, plays an important role in malignant tumorigenesis and progression. However, it is currently lacking research about relationship between SELENBP1 and immunotherapy in colorectal cancer (CRC). METHODS: We first analyzed the expression levels of SELENBP1 based on the Cancer Genome Atlas (TCGA), Oncomine andUALCAN. Chisq.test, Fisher.test, Wilcoxon-Mann-Whitney test and logistic regression were used to analyze the relationship of clinical characteristics with SELENBP1 expression. Then Gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG), Gene set enrichment analysis (GSEA) enrichment analysis to clarify bio-processes and signaling pathways. The cBioPortal was used to perform analysis of mutation sites, types, etc. of SELENBP1. In addition, the correlation of SELENBP1 gene with tumor immune infiltration and prognosis was analyzed using ssGSEA, ESTIMATE, tumor immune dysfunction and rejection (TIDE) algorithm and Kaplan-Meier (KM) Plotter database. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to validate the expression of SELENBP1 in CRC samples and matched normal tissues. Immunohistochemistry (IHC) was further performed to detect the expression of SELENBP1 in CRC samples and matched normal tissues. RESULTS: We found that SELENBP1 expression was lower in CRC compared to normal colorectal tissue and was associated with poor prognosis. The aggressiveness of CRC increased with decreased SELENBP1 expression. Enrichment analysis showed that the SELENBP1 gene was significantly enriched in several pathways, such as programmed death 1 (PD-1) signaling, signaling by interleukins, TCR signaling, collagen degradation, costimulation by the CD28 family. Decreased expression of SELENBP1 was associated with DNA methylation and mutation. Immune infiltration analysis identified that SELENBP1 expression was closely related to various immune cells and immune chemokines/receptors. With increasing SELENBP1 expression, immune and stromal components in the tumor microenvironment were significantly decreased. SELENBP1 expression in CRC patients affects patient prognosis by influencing tumor immune infiltration. Beside this, SELENBP1 expression is closely related to the sensitivity of chemotherapy and immunotherapy. CONCLUSIONS: Survival analysis as well as enrichment and immunoassay results suggest that SELENBP1 can be considered as a promising prognostic biomarker for CRC. SELENBP1 expression is closely associated with immune infiltration and immunotherapy. Collectively, our study provided useful information on the oncogenic role of SELENBP1, contributing to further exploring the underlying mechanisms.

A joint experimental and theoretical study on structural, electronic, and magnetic properties of MnGen - (n = 3-14) clusters.

A systematic structure and property investigation of MnGen - (n = 3-14) was conducted by means of density functional theory coupled with mass-selected anion photoelectron spectroscopy. This combined theoretical and experimental study allows global minimum and coexistence structures to be identified. It is found that the pentagonal bipyramid shape is the basic framework for the nascent growth process of MnGen - (n = 3-10), and from n = 10, the endohedral structures can be found. For n = 12, the anion MnGe12 - cluster probably includes two isomers: a major isomer with a puckered hexagonal prism geometry and a minor isomer with a distorted icosahedron geometry. Specifically, the puckered hexagonal prism isomer follows the Wade-Mingos rules and can be suggested as a new kind of superatom with the magnetic property. Furthermore, the results of adaptive natural density partitioning and deformation density analyses suggest a polar covalent interaction between Ge and Mn for endohedral clusters of MnGe12 -. The spin density and natural population analysis indicate that MnGen - clusters have high magnetic moments localized on Mn. The density of states diagram visually shows the significant spin polarization for endohedral structures and reveals the weak interaction between the Ge 4p orbital and the 4s, 3d orbitals of Mn.

Structural and electronic properties of exohedrally doped neutral silicon clusters LnSin (n = 5, 10; Ln = Sm, Eu, Yb).

Lanthanide-doped silicon clusters have been extensively studied in the fields of optoelectronics, magnetism and nanomaterials during the last decade. Herein, systematic structure searches for typical neutral clusters of lanthanide-doped silicon clusters LnSin (n = 5, 10; Ln = Sm, Eu, Yb) have been performed by means of density functional theory coupled with the "stochastic kicking" global search technique. It is found that the Ln atom in LnSin prefers to locate on the surface of Sin to form an exohedral structure, and this exohedral configuration may dominate the nascent structure of LnSin. The spin density and Mulliken population analyses indicate that LnSin clusters possess remarkable magnetic moments (except for YbSin), which are mainly supplied by the Ln 4f electrons (except for Yb). Density of states visually shows the significant spin polarization for open-shell structures of SmSin and EuSin. As for the YbSin (n = 5, 10) system, it has a closed-shell electronic structure with a large HOMO-LUMO gap of 2.72 eV. Bonding analysis, including localized orbital locator and electron density difference, shows that the Si-Si covalent interaction and Sm-Si electrostatic interaction are important for the structural stability of LnSin.

Probing the stability of neutral and anionic transition-metal-doped golden cage nanoclusters: M@Au16 (M = Sc, Ti, V).

The golden Au16(q) (q = 0, -1) cage is doped systematically with an external atom of different valence electrons: Sc, Ti, and V. The structural, electronic, and magnetic properties of the doped clusters, M@Au16(q) (M = Sc, Ti and V; q = 0, -1) are investigated using the Saunders "Kick" (SK) global search technique combined with density-functional theory (DFT) calculations (SK-DFT). It is found that the closeness of the calculated vertical/adiabatic detachment energy for Ti-doped and V-doped (3.09/3.16 eV for Ti-doped, and 3.31/3.38 eV for V-doped) is consistent with the negligible geometry change between the anionic and neutral ground state structures. The characteristics of the Sc@Au16(-) cluster includes its remarkably high average binding energy and doping energy, which reflects its high stability. The different spectral features between doped M@Au16(-) and pure Au16(-) clusters indicate endohedral structures with larger distortion from the parent Au16(-) cage for the doped clusters. The s electrons of the Au16 cage are observed to transfer to Sc, Ti and V atom for doped M@Au16(q) clusters by natural population analysis (NPA). The magnetic moment of the impurity Sc/Ti/V atom is somewhat quenched. Furthermore, the electron localization function analysis does not reveal strong interactions. The current work shows that the electronic properties of the golden cage can be systematically tuned through doping.

Mesenchymal stem/stromal cells armored by FGF21 ameliorate alcohol-induced liver injury through modulating polarization of macrophages.

BACKGROUND: Alcohol-associated liver disease (ALD) is a major health care challenge worldwide with limited therapeutic options. Although mesenchymal stem/stromal cells (MSCs) represent a newly emerging therapeutic approach to treat ALD, thus far, there have been extensive efforts to try and enhance their efficacy, including genetically engineering MSCs. FGF21, an endocrine stress-responsive hormone, has been shown to regulate energy balance, glucose, and lipid metabolism and to enhance the homing of MSCs toward injured sites. Therefore, the purpose of this study was to investigate whether MSCs that overexpress FGF21 (FGF21-MSCs) improve the therapeutic effect of MSCs in treating ALD. METHODS: Human umbilical cord-derived MSCs served as the gene delivery vehicle for the FGF21 gene. Human umbilical cord-derived MSCs were transduced with the FGF21 gene using lentiviral vectors to mediate FGF21 overexpression. We utilized both chronic Lieber-DeCarli and Gao-binge models of ethanol-induced liver injury to observe the therapeutic effect of FGF21-MSCs. Liver injury was phenotypically evaluated by performing biochemical methods, histology, and inflammatory cytokine levels. RESULTS: Compared with MSCs alone, administration of MSCs overexpressing FGF21(FGF21-MSCs) treatment significantly enhanced the therapeutic effect of ALD in mice, as indicated by the alleviation of liver injury with reduced steatosis, inflammatory infiltration, oxidative stress, and hepatic apoptosis, and the promotion of liver regeneration. Mechanistically, FGF21 could facilitate the immunomodulatory function of MSCs on macrophages by setting metabolic commitment for oxidative phosphorylation, which enables macrophages to exhibit anti-inflammatory inclination. CONCLUSIONS: Our data elucidate that MSC modification by FGF21 could enhance their therapeutic effect in ALD and may help in the exploration of effective MSCs-based cell therapies for the treatment of ALD.

The Identification of Gamma-Glutamyl Hydrolase in Uterine Corpus Endometrial Carcinoma: a Predictive Model and Machine Learning.

BACKGROUND: Poor neoplastic differentiation contributes to the rapid progression of uterine corpus endometrial carcinoma (UCEC). Thus, it is essential to identify candidate genes, clarifying the carcinogenesis and progression of UCEC. METHODS: We screened genes that affect differentiation and prognosis in UCEC. Least absolute selection and shrinkage operator (LASSO) regression, univariate Cox, and multivariate Cox proportional risk regression analyses were performed to screen out γ-glutamyl hydrolase (GGH) as the candidate gene. The clinical value of GGH on prognosis was evaluated. The relationship between GGH and immune infiltration was assessed by CIBERSORT, EPIC, ssGSEA, unsupervised clustering and immunohistochemistry (IHC). Additionally, we investigated the effect of GGH knockdown in vitro. RESULTS: Among the GGH, CDKN2A, and SIX1 genes, the impact of GGH was predominant on immune infiltration in UCEC. A nomogram containing GGH and other clinical features showed good predictive performance via curve analysis (DCA). In the functional analysis, GGH affected differentiation, tumour proliferation, and immune regulation. The immunosuppressive components were enriched in the GGH-high group, with poor immunotherapy efficacy. The study suggests that GGH may influence the progression of UCEC by regulating the glycolytic process. CONCLUSIONS: GGH is closely associated with various immune cell infiltrations. Our study demonstrates the prognostic role of GGH in carcinogenesis in UCEC.

Mesenchymal stromal/stem cells and their extracellular vesicles in liver diseases: insights on their immunomodulatory roles and clinical applications.

Liver disease is a leading cause of mortality and morbidity that is rising globally. Liver dysfunctions are classified into acute and chronic diseases. Various insults, including viral infections, alcohol or drug abuse, and metabolic overload, may cause chronic inflammation and fibrosis, leading to irreversible liver dysfunction. Up to now, liver transplantation could be the last resort for patients with end-stage liver disease. However, liver transplantation still faces unavoidable difficulties. Mesenchymal stromal/stem cells (MSCs) with their broad ranging anti-inflammatory and immunomodulatory properties can be effectively used for treating liver diseases but without the limitation that are associated with liver transplantation. In this review, we summarize and discuss recent advances in the characteristics of MSCs and the potential action mechanisms of MSCs-based cell therapies for liver diseases. We also draw attention to strategies to potentiate the therapeutic properties of MSCs through pre-treatments or gene modifications. Finally, we discuss progress toward clinical application of MSCs or their extracellular vesicles in liver diseases.

Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), as one of the main causes of chronic liver disease worldwide, encompasses a spectrum of liver conditions that are not caused by other etiology, such as overt alcohol consumption, from simple steatosis to more aggressive non-alcoholic steatohepatitis (NASH) that involves liver inflammation and fibrosis, and to the lethal cirrhosis that may result in liver cancer and liver failure. The molecular mechanisms governing the transition from steatosis to NASH remain not fully understood, but the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis, which also correlate with disease progression. With the tremendous advancement in the field of lipidomics in last two decades, a better understanding of the specific role of sphingolipids in fatty liver disease has taken shape. Among the numerous lipid subtypes that accumulate, ceramides are particularly impactful. On the one hand, excessive ceramides deposition in the liver cause hepatic steatosis. On the other hand, ceramides as lipotoxic lipid have significant effects on hepatic inflammation, apoptosis and insulin resistance that contribute to NAFLD. In this review, we summarize and evaluate current understanding of the multiple roles of ceramides in the onset of fatty liver disease and the pathogenic mechanisms underlying their effects, and we also discuss recent advances and challenges in pharmacological interventions targeting ceramide metabolism for the treatment of NAFLD.

GDF15 Ameliorates Liver Fibrosis by Metabolic Reprogramming of Macrophages to Acquire Anti-Inflammatory Properties.

BACKGROUND & AIMS: Liver fibrosis/cirrhosis is significant health burden worldwide, resulting in liver failure or cancer and accounting for many deaths each year. The pathogenesis of liver fibrosis is very complex, which makes treatment challenging. Growth differentiation factor 15 (GDF15), a cysteine knot protein belonging to the transforming growth factor ß (TGF-ß) superfamily, has been shown to play a protective role after tissue injury and to promote a negative energy balance during obesity and diabetes. However, paucity of literature is available about GDF15 function in liver fibrosis. This study aimed to investigate the immunomodulatory role and therapeutic potential of GDF15 in progression of hepatic fibrosis. METHODS: GDF15 expression was studied in patients with fibrosis/cirrhosis and in 2 murine models of liver fibrosis, including mice treated with CCl4 or DDC diet. GDF15 involvement in the pathogenesis of liver fibrosis was assessed in Gdf15 knockout mouse using both CCl4 and DDC diet experimental models. We used the CCl4 and/or DDC diet-induced liver fibrosis model to examine the antifibrotic and anti-inflammatory effects of AAV8-mediated GDF15 overexpression in hepatocytes or recombinant mouse GDF15. RESULTS: GDF15 expression is decreased in the liver of animal models and patients with liver fibrosis/cirrhosis compared with those without liver disease. In vivo studies showed that GDF15 deficiency aggravated CCl4 and DDC diet-induced liver fibrosis, while GDF15 overexpression mediated by AAV8 or its recombinant protein alleviated CCl4 and/or DDC diet-induced liver fibrosis. In Gdf15 knockout mice, the intrahepatic microenvironment that developed during fibrosis showed relatively more inflammation, as demonstrated by enhanced infiltration of monocytes and neutrophils and increased expression of proinflammatory factors, which could be diminished by AAV8-mediated GDF15 overexpression in hepatocytes. Intriguingly, GDF15 exerts its effects by reprogramming the metabolic pathways of macrophages to acquire an oxidative phosphorylation-dependent anti-inflammatory functional fate. Furthermore, adoptive transfer of GDF15-preprogrammed macrophages to mouse models of liver fibrosis induced by CCl4 attenuated inflammation and alleviated the progression of liver fibrosis. CONCLUSION: GDF15 ameliorates liver fibrosis via modulation of liver macrophages. Our data implicate the importance of the liver microenvironment in macrophage programming during liver fibrosis and suggest that GDF15 is a potentially attractive therapeutic target for the treatment of patients with liver fibrosis.

Curcumin alleviates orofacial allodynia and improves cognitive impairment via regulating hippocampal synaptic plasticity in a mouse model of trigeminal neuralgia.

OBJECTIVE: Cognitive impairment, one of the most prevalent complications of trigeminal neuralgia, is troubling for patients and clinicians due to limited therapeutic options. Curcumin shows antinociception and neuroprotection pharmacologically, suggesting that it may have therapeutic effect on this complication. This study aimed to investigate whether curcumin alleviates orofacial allodynia and improves cognitive impairment by regulating hippocampal CA1 region synaptic plasticity in trigeminal neuralgia. METHODS: A mouse model of trigeminal neuralgia was established by partially transecting the infraorbital nerve (pT-ION). Curcumin was administered by gavage twice daily for 14 days. Nociceptive thresholds were measured using the von Frey and acetone test, and the cognitive functions were evaluated using the Morris water maze test. Dendritic spines and synaptic ultrastructures in the hippocampal CA1 area were observed by Golgi staining and transmission electron microscopy. RESULTS: Curcumin intervention increased the mechanical and cold pain thresholds of models. It decreased the escape latency and distance to the platform and increased the number of platform crossings and dwell time in the target quadrant of models, and improved spatial learning and memory deficits. Furthermore, it partially restored the disorder of the density and proportion of dendritic spines and the abnormal density and structure of synapses in the hippocampal CA1 region of models. CONCLUSION: Curcumin alleviates abnormal orofacial pain and cognitive impairment in pT-ION mice by a mechanism that may be related to the synaptic plasticity of hippocampal CA1, suggesting that curcumin is a potential strategy for repairing cognitive dysfunction under long-term neuropathic pain conditions.

Probing the structural and electronic properties of small vanadium monoxide clusters.

The structural evolution and bonding of a series of early transition-metal oxide clusters, V(n)O(q) (n = 3-9, q = 0,-1), have been investigated with the aid of previous photoelectron spectroscopy (PES) and theoretical calculations. For each vanadium monoxide cluster, many low-lying isomers are generated using the Saunders "Kick" global minimum stochastic search method. Theoretical electron detachment energies (both vertical and adiabatic) were compared with the experimental measurements to verify the ground states of the vanadium monoxide clusters obtained from the DFT calculations. The results demonstrate that the combination of photoelectron spectroscopy experiments and DFT calculation is not only powerful for obtaining the electronic and atomic structures of size-selected clusters, but also valuable in resolving structurally and energetically close isomers. The second difference energies and adsorption energies as a function of the cluster size exhibit a pronounced even-odd alternation phenomenon. The adsorption energies of one O atom on the anionic (6.64 → 8.16 eV) and neutral (6.41 → 8.13 eV) host vanadium clusters are shown to be surprisingly high, suggesting strong capabilities to activate O by structural defects in vanadium oxides.

Probing the structural and electronic properties of small vanadium dioxide clusters by density functional theory and comparison with experimental photoelectron spectroscopy.

The structural evolution and bonding of a series of early transition-metal dioxide clusters, V(n)O(2)(q)(n = 3-9, q = 0, -1), have been investigated using density functional theory (DFT) calculations and the results are compared with experimental literature data. For each vanadium dioxide cluster, many low-lying isomers are generated using the Saunders "Kick" global minimum stochastic search method. Theoretical electron detachment energies (both vertical and adiabatic) were compared with the experimental measurements to verify the ground states of the vanadium dioxide clusters obtained from the DFT calculations. Five kinds of dissociative adsorption configurations of ground-state structure of V(n)O(2)(q) are identified. The dissociative adsorption of O(2) on V(n)(-1, 0) is more favorable than O(2) molecular adsorption. Furthermore, the adsorption energy of O(2) is higher than that of a single atom on the bare V(n)(-1, 0) clusters, but less than twice the adsorption energy for an atom, indicating that O(2) being adsorbed on vanadium clusters are more difficult than single O atom adsorbed on vanadium clusters.

Relations between plasma von Willebrand factor or endothelin-1 and restenosis following carotid artery stenting.

OBJECTIVE: This study was designed to investigate the relation between plasma von Willebrand factor (VWF) or endothelin-1 (ET-1) and post-carotid artery stenting (CAS) restenosis. MATERIALS AND METHODS: Plasma levels of VWF and ET-1 were measured in 61 patients (36 males, mean age 64.4 ± 6.8 years) before and after CAS. The mean follow-up time was 13.8 ± 1.7 months (range, 6-63). In-stent restenosis was defined as a >10% narrowing of the vascular lumen with or without ischemic symptoms following CAS. RESULTS: In-stent restenosis was identified in 14 (23%) patients, including 3 with >50% restenosis. In the restenosis group, mean VWF and ET-1 levels at 2 weeks, 1 and 6 months after CAS were higher than the baseline levels (p < 0.05 or p < 0.01). Mean levels of VWF and ET-1 in the restenosis group were higher than in the non-restenosis group within 6 months after CAS (p < 0.05 or p < 0.01). CONCLUSION: Persistent elevation in plasma VWF and ET-1 within the first 6 months of CAS was found in patients with in-stent restenosis.

Microsolvation of Co- in water: Density functional theory calculations coupled with stochastic kicking method.

The hydrated clusters [Formula: see text] (n = 1-4) in gas phase are studied by density functional theory calculations (DFT) coupled with stochastic kicking method. The global minimum structure of [Formula: see text] exhibits low-symmetry pattern since only one H atom of water molecules interact with Co- ion and other ones associate with a network of hydrogen bonds. The Co- ion prefers to locate at vertex site of the water molecular clusters in such way to reduce the repulsion with O atom. These results elucidate the formation of these low-lying isomers are determined by the delicate balance between ion-water and water-water interactions.