RIG-I contributes to keratinocyte proliferation and wound repair by inducing TIMP-1 expression through NF-κB signaling pathway.

Epithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re-epithelialization. In this study, we examined the functional role of retinoic acid inducible-gene I (RIG-I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP-1 expression. We found that RIG-I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin-induced diabetic mice. Moreover, mice lacking RIG-I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG-I promoted keratinocyte proliferation and wound repair by inducing TIMP-1 via the NF-κB signaling pathway. Indeed, recombinant TIMP-1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58-/- and diabetic mice in vivo. In summary, we demonstrated that RIG-I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.

Atomic Layers of B2 CuPd on Cu Nanocubes as Catalysts for Selective Hydrogenation.

The search for highly active and selective catalysts with high precious metal atom utilization efficiency has attracted increasing interest in both the fundamental synthesis of materials and important industrial reactions. Here, we report the synthesis of Pd-Cu nanocubes with a Cu core and an ordered B2 intermetallic CuPd shell with controllable atomic layers on the surface (denoted as Cu/B2 CuPd), which can efficiently and robustly catalyze the selective hydrogenation of acetylene (C2H2) to ethylene (C2H4) under mild conditions. The optimized Cu/B2 CuPd with a Pd loading of 9.5 at. % exhibited outstanding performance in the C2H2 semi-hydrogenation with 100% C2H2 conversion and 95.2% C2H4 selectivity at 90 °C. We attributed this outstanding performance to the core/shell structure with a high surface density of active Pd sites isolated by Cu in the B2 intermetallic matrix, representing a structural motif of single-atom alloys (SAAs) on the surface. The combined experimental and computational studies further revealed that the electronic states of Pd and Cu are modulated by SAAs from the synergistic effect between Pd and Cu, leading to enhanced performance compared with pristine Pd and Cu catalysts. This study provides a new synthetic methodology for making single-atom catalysts with high precious metal atom utilization efficiency, enabling simultaneous tuning of both geometric and electronic structures of Pd active sites for enhanced catalysis.

Metal-Metal Oxide Catalytic Interface Formation and Structural Evolution: A Discovery of Strong Metal-Support Bonding, Ordered Intermetallics, and Single Atoms.

In-depth investigation of metal-metal oxide interactions and their corresponding evolution is of paramount importance to heterogeneous catalysis as it allows the understanding and maneuvering of the structure of catalytic motifs. Herein, using a series of core/shell metal/iron oxide (M/FeOx, M = Pd, Pt, Au) nanoparticles and through a combination of in situ and ex situ electron and X-ray investigations, we revealed anomalous and dissimilar M-FeOx interactions among different systems under reducing conditions. Pd interacts strongly with FeOx after high-temperature reductive treatment, featured by the formation of Pd single atoms in the FeOx matrix and increased Pd-Fe bonding, while Pt transforms into ordered PtFe intermetallics and Pt single atoms immediately upon the coating of FeOx. In contrast, Au does not manifest strong bonding with FeOx. As a proof of concept of tailoring metal-metal oxide interactions for catalysis, optimized Pd/FeOx demonstrates 100% conversion and 86.5% selectivity at 60 °C for acetylene semihydrogenation.

The predictive value of CT-based radiomics in differentiating indolent from invasive lung adenocarcinoma in patients with pulmonary nodules.

OBJECTIVES: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are assumed to be indolent lung adenocarcinoma with excellent prognosis. We aim to identify these lesions from invasive adenocarcinoma (IA) by a radiomics approach. METHODS: This retrospective study was approved by institutional review board with a waiver of informed consent. Pathologically confirmed lung adenocarcinomas manifested as lung nodules less than 3 cm were retrospectively identified. In-house software was used to quantitatively extract 60 CT-based radiomics features quantifying nodule's volume, intensity and texture property through manual segmentation. In order to differentiate AIS/MIA from IA, least absolute shrinkage and selection operator (LASSO) logistic regression was used for feature selection and developing radiomics signatures. The predictive performance of the signature was evaluated via receiver operating curve (ROC) and calibration curve, and validated using an independent cohort. RESULTS: 402 eligible patients were included and divided into the primary cohort (n = 207) and the validation cohort (n = 195). Using the primary cohort, we developed a radiomics signature based on five radiomics features. The signature showed good discrimination between MIA/AIS and IA in both the primary and validation cohort, with AUCs of 0.95 (95% CI, 0.91-0.98) and 0.89 (95% CI, 0.84-0.93), respectively. Multivariate logistic analysis revealed that the signature (OR, 13.3; 95% CI, 6.2-28.5; p < 0.001) and gender (OR, 3.5; 95% CI, 1.2-10.9; p = 0.03) were independent predictors of indolent lung adenocarcinoma. CONCLUSION: The signature based on radiomics features helps to differentiate indolent from invasive lung adenocarcinoma, which might be useful in guiding the intervention choice for patients with pulmonary nodules. KEY POINTS: • Based on radiomics features, a signature is established to differentiate adenocarcinoma in situ and minimally invasive adenocarcinoma from invasive lung adenocarcinoma.

Crystal Structural Effect of AuCu Alloy Nanoparticles on Catalytic CO Oxidation.

Controlling the physical and chemical properties of alloy nanoparticles (NPs) is an important approach to optimize NP catalysis. Unlike other tuning knobs, such as size, shape, and composition, crystal structure has received limited attention and not been well understood for its role in catalysis. This deficiency is mainly due to the difficulty in synthesis and fine-tuning of the NPs' crystal structure. Here, Exemplifying by AuCu alloy NPs with face centered cubic (fcc) and face centered tetragonal (fct) structure, we demonstrate a remarkable difference in phase segregation and catalytic performance depending on the crystal structure. During the thermal treatment in air, the Cu component in fcc-AuCu alloy NPs segregates more easily onto the alloy surface as compared to that in fct-AuCu alloy NPs. As a result, after annealing at 250 °C in air for 1 h, the fcc- and fct-AuCu alloy NPs are phase transferred into Au/CuO and AuCu/CuO core/shell structures, respectively. More importantly, this variation in heterostructures introduces a significant difference in CO adsorption on two catalysts, leading to a largely enhanced catalytic activity of AuCu/CuO NP catalyst for CO oxidation. The same concept can be extended to other alloy NPs, making it possible to fine-tune NP catalysis for many different chemical reactions.

Tailoring N-Terminated Defective Edges of Porous Boron Nitride for Enhanced Aerobic Catalysis.

Tailoring terminated edge of hexagonal boron nitride (h-BN) for enhancing catalysis has turned to be an imperative for the rational design of a highly active aerobic catalyst. Herein, a tailoring N-terminated porous BN (P-BN) strategy is reported with a zinc (Zn) salt as a dual-functional template. The Zn salt acts as both an in situ template and an N-terminated defective edges directing agent. The zinc salt template turns to Zn nanoparticles (Zn NPs) and functions as physical spacers, which are subsequently removed at a higher temperature, for producing P-BN, whose high surface area is high to 1579 m2 g-1 . Moreover, because of the lower electronegativity of Zn, boron (B) atoms are partly replaced by Zn atoms and ultimately preferred to N-terminated edges with the volatilization of Zn NPs. Owing to the moderate dissociative energy of oxygen atoms on N-terminated edges, the N-terminated edges are proved to be the origin of an enhanced aerobic catalytic activity by density functional theory (DFT) calculations. Moreover, the DFT calculation result is experimentally verified.

Development and validation of a nomogram to estimate the pretest probability of cancer in Chinese patients with solid solitary pulmonary nodules: A multi-institutional study.

OBJECTIVES: To develop and validate a nomogram to estimate the pretest probability of malignancy in Chinese patients with solid solitary pulmonary nodule (SPN). MATERIALS AND METHODS: A primary cohort of 1798 patients with pathologically confirmed solid SPNs after surgery was retrospectively studied at five institutions from January 2014 to December 2015. A nomogram based on independent prediction factors of malignant solid SPN was developed. Predictive performance also was evaluated using the calibration curve and the area under the receiver operating characteristic curve (AUC). RESULTS: The mean age of the cohort was 58.9 ± 10.7 years. In univariate and multivariate analysis, age; history of cancer; the log base 10 transformations of serum carcinoembryonic antigen value; nodule diameter; the presence of spiculation, pleural indentation, and calcification remained the predictive factors of malignancy. A nomogram was developed, and the AUC value (0.85; 95%CI, 0.83-0.88) was significantly higher than other three models. The calibration cure showed optimal agreement between the malignant probability as predicted by nomogram and the actual probability. CONCLUSIONS: We developed and validated a nomogram that can estimate the pretest probability of malignant solid SPNs, which can assist clinical physicians to select and interpret the results of subsequent diagnostic tests.

Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis.

Psoriasis is a chronic recurrent inflammatory skin disorder characterized by the dysregulated cross-talk between epidermal keratinocytes and immune cells, leading to keratinocyte hyperproliferation. Several studies demonstrated that Wnt pathway genes were differentially expressed in psoriatic plaques and likely were involved in the pathophysiology of disease. However, the molecular mechanisms underlying Wnt signaling regulation in epidermal hyperplasia in psoriasis remain largely unknown. We report that the expression of secreted frizzled-related protein (SFRP) 4, a negative regulator of the Wnt signaling pathway, was diminished in lesional skin of mouse models and patients with psoriasis. SFRP4 directly inhibited excessive keratinocyte proliferation evoked by proinflammatory cytokines in vitro. Pharmacological inhibition of Wnt signaling or intradermal injection of SFRP4 decreased the severity of the psoriasiform skin phenotype in vivo, including decreased acanthosis and reduced leukocyte infiltration. Mechanistically, we identified that aberrant promoter methylation resulted in epigenetic downregulation of SFRP4 in inflamed skin of patients with psoriasis and in the IL-23-induced mouse model. Our findings suggest that this epigenetic event is critically involved in the pathogenesis of psoriasis, and the downregulation of SFRP4 by CpG island methylation is one possible mechanism contributing to the hyperplasia of epidermis in the disease.

Experimental Study on the Protection of Agrimony Extracts from Different Extracting Methods against Cerebral Ischemia-Reperfusion Injury.

Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony. Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO. Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry, histological changes (hematoxylin-eosin staining), Na+/K+-ATPase, Ca2+-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70) (quantitative real-time PCR). Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05), indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68, P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na+/K+-ATPase and Ca2+-ATPase reduced in the MCAO group (3.67±0.48 U/mg, 1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65, P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group. Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.

Surfactant-Assisted Stabilization of Au Colloids on Solids for Heterogeneous Catalysis.

The stabilization of surfactant-assisted synthesized colloidal noble metal nanoparticles (NPs, such as Au NPs) on solids is a promising strategy for preparing supported nanocatalysts for heterogeneous catalysis because of their uniform particle sizes, controllable shapes, and tunable compositions. However, surfactant removal to obtain clean surfaces for catalysis through traditional approaches (such as solvent extraction and thermal decomposition) can easily induce the sintering of NPs, greatly hampering their use in synthesis of novel catalysts. Such unwanted surfactants have now been utilized to stabilize NPs on solids by a simple yet efficient thermal annealing strategy. After being annealed in N2 flow, the surface-bound surfactants are carbonized in situ as sacrificial architectures that form a conformal coating on NPs and assist in creating an enhanced metal-support interaction between NPs and substrate, thus slowing down the Ostwald ripening process during post-oxidative calcination to remove surface covers.

New approach to fully ordered fct-FePt nanoparticles for much enhanced electrocatalysis in acid.

Fully ordered face-centered tetragonal (fct) FePt nanoparticles (NPs) are synthesized by thermal annealing of the MgO-coated dumbbell-like FePt-Fe3O4 NPs followed by acid washing to remove MgO. These fct-FePt NPs show strong ferromagnetism with room temperature coercivity reaching 33 kOe. They serve as a robust electrocatalyst for the oxygen reduction reaction (ORR) in 0.1 M HClO4 and hydrogen evolution reaction (HER) in 0.5 M H2SO4 with much enhanced activity (the most active fct-structured alloy NP catalyst ever reported) and stability (no obvious Fe loss and NP degradation after 20 000 cycles between 0.6 and 1.0 V (vs RHE)). Our work demonstrates a reliable approach to FePt NPs with much improved fct-ordering and catalytic efficiency for ORR and HER.

Controlled Gas Exfoliation of Boron Nitride into Few-Layered Nanosheets.

The controlled exfoliation of hexagonal boron nitride (h-BN) into single- or few-layered nanosheets remains a grand challenge and becomes the bottleneck to essential studies and applications of h-BN. Here, we present an efficient strategy for the scalable synthesis of few-layered h-BN nanosheets (BNNS) using a novel gas exfoliation of bulk h-BN in liquid N2 (L-N2 ). The essence of this strategy lies in the combination of a high temperature triggered expansion of bulk h-BN and the cryogenic L-N2 gasification to exfoliate the h-BN. The produced BNNS after ten cycles (BNNS-10) consisted primarily of fewer than five atomic layers with a high mass yield of 16-20 %. N2 sorption and desorption isotherms show that the BNNS-10 exhibited a much higher specific surface area of 278 m(2) g(-1) than that of bulk BN (10 m(2) g(-1) ). Through the investigation of the exfoliated intermediates combined with a theoretical calculation, we found that the huge temperature variation initiates the expansion and curling of the bulk h-BN. Subseqently, the L-N2 penetrates into the interlayers of h-BN along the curling edge, followed by an immediate drastic gasification of L-N2 , further peeling off h-BN. This novel gas exfoliation of high surface area BNNS not only opens up potential opportunities for wide applications, but also can be extended to produce other layered materials in high yields.

Constructing Hierarchical Interfaces: TiO2-Supported PtFe-FeO(x) Nanowires for Room Temperature CO Oxidation.

In this communication, we report a facile approach to constructing catalytic active hierarchical interfaces in one-dimensional (1D) nanostructure, exemplified by the synthesis of TiO2-supported PtFe-FeO(x) nanowires (NWs). The hierarchical interface, constituting atomic level interactions between PtFe and FeO(x) within each NW and the interactions between NWs and support (TiO2), enables CO oxidation with 100% conversion at room temperature. We identify the role of the two interfaces by probing the CO oxidation reaction with isotopic labeling experiments. Both the oxygen atoms (Os) in FeO(x) and TiO2 participate in the initial CO oxidation, facilitating the reaction through a redox pathway. Moreover, the intact 1D structure leads to the high stability of the catalyst. After 30 h in the reaction stream, the PtFe-FeO(x)/TiO2 catalyst exhibits no activity decay. Our results provide a general approach and new insights into the construction of hierarchical interfaces for advanced catalysis.

Stable Cobalt Nanoparticles and Their Monolayer Array as an Efficient Electrocatalyst for Oxygen Evolution Reaction.

Monodisperse cobalt (Co) nanoparticles (NPs) were synthesized and stabilized against oxidation via reductive annealing at 600 °C. The stable Co NPs are active for catalyzing the oxygen evolution reaction (OER) in 0.1 M KOH, producing a current density of 10 mA/cm(2) at an overpotential of 0.39 V (1.62 V vs RHE, no iR-correction). Their catalysis is superior to the commercial Ir catalyst in both activity and stability. These Co NPs are also assembled into a monolayer array on the working electrode, allowing the detailed study of their intrinsic OER activity. The Co NPs in the monolayer array show 15 times higher turnover frequency (2.13 s(-1)) and mass activity (1949 A/g) than the NPs deposited on conventional carbon black (0.14 s(-1) and 126 A/g, respectively) at an overpotential of 0.4 V. These stable Co NPs are a promising new class of noble-metal-free catalyst for water splitting.

Surface Profile Control of FeNiPt/Pt Core/Shell Nanowires for Oxygen Reduction Reaction.

Monodisperse core/shell FeNiPt/FePt nanowires (4.5 × 20-50 nm) are synthesized by seed-mediated growth of FePt over the pre-made 2.5 nm wide FeNiPt nanowires. The surface profile of the FeNiPt/FePt nanowires is tailored by acid and thermal treatment. The FeNiPt/Pt-skin nanowires show higher activities than the FeNiPt/Pt-skeleton nanowires.

Autocrine interleukin-6 drives skin-derived mesenchymal stem cell trafficking via regulating voltage-gated Ca(2+) channels.

Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential for a variety of diseases including autoimmune disorders. A fundamental requirement for MSC-mediated in vivo immunosuppression is their effective trafficking. However the mechanism underlying MSC trafficking remains elusive. Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin-6 (IL-6) in inflammatory conditions. Disruption of the il6 or its signaling transducer gp130 blocks voltage-gated calcium (Ca(2+) ) channels (VGCC) critically required for cell contraction involved in the sequential adhesion and de-adhesion events during S-MSC migration. Deletion of il6 gene leads to a severe defect in S-MSC's trafficking and immunosuppressive function in vivo. Thus, this unexpected requirement of autocrine IL-6 for activating Ca(2+) channels uncovers a previously unrecognized link between the IL-6 signaling and the VGCC and provides novel mechanistic insights for the trafficking and immunomodulatory activities of S-MSCs.

Monolayer assembly of ferrimagnetic Co(x)Fe(3-x)O4 nanocubes for magnetic recording.

We report a facile synthesis of monodisperse ferrimagnetic Co(x)Fe(3-x)O4 nanocubes (NCs) through thermal decomposition of Fe(acac)3 and Co(acac)2 (acac = acetylacetonate) in the presence of oleic acid and sodium oleate. The sizes of the NCs are tuned from 10 to 60 nm, and their composition is optimized at x = 0.6 to show strong ferrimagnetism with the 20 nm Co0.6Fe2.4O4 NCs showing a room temperature Hc of 1930 Oe. The ferrimagnetic NCs are self-assembled at the water-air interface into a large-area (in square centimeter) monolayer array with a high packing density and (100) texture. The 20 nm NC array can be recorded at linear densities ranging from 254 to 31 kfci (thousand flux changes per inch). The work demonstrates the great potential of solution-phase synthesis and self-assembly of magnetic array for magnetic recording applications.

Controlled Anisotropic Growth of Co-Fe-P from Co-Fe-O Nanoparticles.

A facile approach to bimetallic phosphides, Co-Fe-P, by a high-temperature (300 °C) reaction between Co-Fe-O nanoparticles and trioctylphosphine is presented. The growth of Co-Fe-P from the Co-Fe-O is anisotropic. As a result, Co-Fe-P nanorods (from the polyhedral Co-Fe-O nanoparticles) and sea-urchin-like Co-Fe-P (from the cubic Co-Fe-O nanoparticles) are synthesized with both the nanorod and the sea-urchin-arm dimensions controlled by Co/Fe ratios. The Co-Fe-P structure, especially the sea-urchin-like (Co(0.54)Fe(0.46))2P, shows enhanced catalysis for the oxygen evolution reaction in KOH with its catalytic efficiency surpassing the commercial Ir catalyst. Our synthesis is simple and may be readily extended to the preparation of other multimetallic phosphides for important catalysis and energy storage applications.

Tuning nanoparticle structure and surface strain for catalysis optimization.

Controlling nanoparticle (NP) surface strain, i.e. compression (or stretch) of surface atoms, is an important approach to tune NP surface chemistry and to optimize NP catalysis for chemical reactions. Here we show that surface Pt strain in the core/shell FePt/Pt NPs with Pt in three atomic layers can be rationally tuned via core structural transition from cubic solid solution [denoted as face centered cubic (fcc)] structure to tetragonal intermetallic [denoted as face centered tetragonal (fct)] structure. The high activity observed from the fct-FePt/Pt NPs for oxygen reduction reaction (ORR) is due to the release of the overcompressed Pt strain by the fct-FePt as suggested by quantum mechanics-molecular mechanics (QM-MM) simulations. The Pt strain effect on ORR can be further optimized when Fe in FePt is partially replaced by Cu. As a result, the fct-FeCuPt/Pt NPs become the most efficient catalyst for ORR and are nearly 10 times more active in specific activity than the commercial Pt catalyst. This structure-induced surface strain control opens up a new path to tune and optimize NP catalysis for ORR and many other chemical reactions.

Monodisperse M(x)Fe(3-x)O4 (M = Fe, Cu, Co, Mn) nanoparticles and their electrocatalysis for oxygen reduction reaction.

Sub-10 nm nanoparticles (NPs) of M(II)-substituted magnetite MxFe3-xO4 (MxFe1-xO•Fe2O3) (M = Mn, Fe, Co, Cu) were synthesized and studied as electrocatalysts for oxygen reduction reaction (ORR) in 0.1 M KOH solution. Loaded on commercial carbon support, these MxFe3-xO4 NPs showed the M(II)-dependent ORR catalytic activities with MnxFe3-xO4 being the most active followed by CoxFe3-xO4, CuxFe3-xO4, and Fe3O4. The ORR activity of the MnxFe3-xO4 was further tuned by controlling x and MnFe2O4 NPs were found to be as efficient as the commercial Pt in catalyzing ORR. The MnFe2O4 NPs represent a new class of highly efficient non-Pt catalyst for ORR in alkaline media.