An Active and Regenerable Nanometric High-Entropy Catalyst for Efficient Propane Dehydrogenation.

Propane dehydrogenation (PDH) is crucial for propylene production, but commercially employed Pt-based catalysts face susceptibility to deactivation due to the Pt sintering during reaction and regeneration steps. Here, we report a SiO2 supported nanometric (MnCoCuZnPt) high-entropy PDH catalyst with high activity and stability. The catalyst exhibited a super high propane conversion of 56.6% with 94% selectivity of propylene at 600 °C. The propylene productivity reached 68.5 molC3H6·gPt-1·h-1, nearly three times that of Pt/SiO2 (23.5 molC3H6·gPt-1·h-1) under a weight hourly space velocity of 60 h-1. In a high-entropy nanoparticle, Pt atoms were atomically dispersed through coordination with other metals and exhibited a positive charge, thereby showcasing remarkable catalytic activity. The high-entropy effect contributes to the catalyst a superior stability with a low deactivation constant of 0.0004 h-1 during 200 hours of reaction under the industrial gas composition at 550 °C. Such high-entropy PDH catalyst is easy regenerated through simple air combustion of deposited coke. After the fourth consecutive regeneration cycle, satisfactory catalytic stability was observed, and the element distribution of spent catalysts almost returned to their initial state, with no detectable Pt sintering. This work provides new insights into designing active, stable, and regenerable novel PDH catalysts.

A thermodynamic model of the surface hydroxylation of γ-Al2O3.

Rational design of γ-alumina-based catalysts relies on an extensive understanding of the distribution of hydroxyl groups on the surface of γ-alumina and their physicochemical properties, which remain unclear and challenging to determine experimentally due to the structural complexity. In this work, by means of DFT and thermodynamic calculations, various hydroxylation modes of γ-alumina (110) and (100) surfaces at different OH coverages were evaluated, based on which a thermodynamic model to reflect the relationship between temperature and the surface structure was established and the stable hydroxylation modes under experimental conditions were predicted. This enables us to identify the experimentally measured IR spectra. The effect of hydroxyl coverages on the surface Lewis acidity was then analyzed, showing that the presence of hydroxyl groups could promote the Lewis acidity of neighboring Al sites. This work provides fundamental insights into the molecular level understanding of the surface properties of γ-alumina and benefits the rational design of alumina-based catalysts.

Multidimensional plasma lipid composition and its causal association with type 2 diabetes mellitus: A Mendelian randomization study.

BACKGROUND AND AIM: Recent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment. METHODS AND RESULTS: This study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034-1.109, P = 1.36 × 10-4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028-1.077, P = 1.80 × 10-5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108-1.243, P = 4.65 × 10-8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892-0.966, P = 2.37 × 10-4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897-0.967, P = 2.37 × 10-4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812-0.935, P = 1.24 × 10-4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified. CONCLUSIONS: This MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.

Balancing the Kinetic and Thermodynamic Synergetic Effect of Doped Carbon Molecular Sieves for Selective Separation of C2H4/C2H6.

Selective separation of ethylene and ethane (C2H4/C2H6) is a formidable challenge due to their close molecular size and boiling point. Compared to industry-used cryogenic distillation, adsorption separation would offer a more energy-efficient solution when an efficient adsorbent is available. Herein, a class of C2H4/C2H6 separation adsorbents, doped carbon molecular sieves (d-CMSs) is reported which are prepared from the polymerization and subsequent carbonization of resorcinol, m-phenylenediamine, and formaldehyde in ethanol solution. The study demonstrated that the polymer precursor themselves can be a versatile platform for modifying the pore structure and surface functional groups of their derived d-CMSs. The high proportion of pores centered at 3.5 Å in d-CMSs contributes significantly to achieving a superior kinetic selectivity of 205 for C2H4/C2H6 separation. The generated pyrrolic-N and pyridinic-N functional sites in d-CMSs contribute to a remarkable elevation of Henry selectivity to 135 due to the enhancement of the surface polarity in d-CMSs. By balancing the synergistic effects of kinetics and thermodynamics, d-CMSs achieve efficient separation of C2H4/C2H6. Polymer-grade C2H4 of 99.71% purity can be achieved with 75% recovery using the devised d-CMSs as reflected in a two-bed vacuum swing adsorption simulation.

Therapeutic Effectiveness of Leukocyte- and Platelet-rich Fibrin for Diabetic Foot Ulcers: A Retrospective Study.

OBJECTIVE: Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Leukocyte- and platelet-rich fibrin (L-PRF) is a second-generation autologous platelet-rich plasma. This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice. METHODS: Patients with DFU who received L-PRF treatment and standard of care (SOC) from 2018 to 2019 in Tongji Hospital were enrolled. The clinical information including patient characteristics, wound evaluation (area, severity, infection, blood supply), SOC of DFU, and images of ulcers was retrospectively extracted and analyzed. L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction (PVR) greater than 80%. Therapeutic effectiveness, including overall PVR and the overall and weekly healing rates, was evaluated. RESULTS: Totally, 26 patients with DFU were enrolled, and they had an ulcer duration of 47.0 (35.0, 72.3) days. The severity and infection of ulcers varied, as indicated by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) scores of 2-6, Wagner grades of 1-4, and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) scores of 2-4. The initial ulcer volume before L-PRF treatment was 4.94 (1.50, 13.83) cm3, and the final ulcer volume was 0.35 (0.03, 1.76) cm3. The median number of L-PRF doses was 3 (2, 5). A total of 11 patients achieved complete epithelialization after the fifth week of treatment, and 19 patients achieved at least an 80% volume reduction after the seventh week. The overall wound-healing rate was 1.47 (0.63, 3.29) cm3/week, and the healing rate was faster in the first 2 weeks than in the remaining weeks. Concurrent treatment did not change the percentage of complete epithelialization or healing rate. CONCLUSION: Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index, SINBAD score, or Wagner grade, indicating that this method is appropriate for DFU treatment under different clinical conditions.

Spatially distributed metabolites SWEETen the root for microbes.

Limited understanding exists on the spatial configuration of underground plant-microbe interactions. In this issue of Cell Host & Microbe, Loo et al. illustrate the sugar transporter-involved interdependent interaction between root metabolites and microbial spatial colonization, providing insights into metabolic-associated organization of plant-microbe interactions.

Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced ß-Cell Dysfunction by Activating Nrf2.

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent ß-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet ß-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent ß-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated ß-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated ß-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced ß-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of ß-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.

A new method for vascular age estimation based on relative risk difference in vascular aging.

OBJECTIVE: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk. METHODS: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA. RESULTS: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease. CONCLUSION: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors.

Synergistic evolution of water-energy-food system resilience and efficiency in urban agglomerations.

With increasing internal and external risks to the WEF system, a single emphasis on efficiency or a lopsided pursuit of resilience can lead to difficulties in adapting to complex changes and resource redundancy. Revealing the synergistic evolutionary characteristics between efficiency and resilience of the WEF system is an effective method to deal with systemic internal and external risks. However, the current study of the WEF system lacks a synergistic perspective on resilience and efficiency. Thus, taking Chengdu-Chongqing Economic Circle (CCEC) as the research object and its geospatial boundary as the system boundary, this paper adopted the entropy-topsis model to evaluate the WEF resilience, and applied the super-efficient SBM model to measure the WEF efficiency accurately, which fully considered the non-expected outputs in the process of resource utilization. Then, applying the development coordination degree model, the synergistic relationship between the two was measured. The results indicated that: the average value of WEF resilience in CCEC increased from 0.414 to 0.485 and showed spatial characteristics of west＞east＞central. The WEF efficiency interval was 0.79-0.93, and cities with average WEF efficiency reaching the effective production frontier accounted for only 37.5%. The clustered distribution of the synergy levels intensified. The number of cities with primary, medium, more advanced, and advanced levels was 6, 6, 1, and 3, respectively, with primary and medium synergy levels dominating. The findings suggest that cities should strengthen regional exchanges and formulate targeted measures based on their own situations. In addition, CCEC should possess a comprehensive understanding of the interdependencies and conflicts that arise between resilience and efficiency throughout the decision-making procedure.

Microbial species pool-mediated diazotrophic community assembly in crop microbiomes during plant development.

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil-plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with Methylobacterium, Azospirillum, Bradyrhizobium, and Rhizobium. Furthermore, eight dominant taxa belonging to Azospirillum and Methylobacterium were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to Pseudomonas mendocina. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.IMPORTANCEPlants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.

Streptomyces-triggered coordination between rhizosphere microbiomes and plant transcriptome enables watermelon Fusarium wilt resistance.

The use of microbial inoculant is a promising strategy to improve plant health, but their efficiency often faces challenges due to difficulties in successful microbial colonization in soil environments. To this end, the application of biostimulation products derived from microbes is expected to resolve these barriers via direct interactions with plants or soil pathogens. However, their effectiveness and mechanisms for promoting plant growth and disease resistance remain elusive. In this study, we showed that root irrigation with the extracts of Streptomyces ahygroscopicus strain 769 (S769) solid fermentation products significantly reduced watermelon Fusarium wilt disease incidence by 30% and increased the plant biomass by 150% at a fruiting stage in a continuous cropping field. S769 treatment led to substantial changes in both bacterial and fungal community compositions, and induced a highly interconnected microbial association network in the rhizosphere. The root transcriptome analysis further suggested that S769 treatment significantly improved the expression of the MAPK signalling pathway, plant hormone signal transduction and plant-pathogen interactions, particular those genes related to PR-1 and ethylene, as well as genes associated with auxin production and reception. Together, our study provides mechanistic and empirical evidences for the biostimulation products benefiting plant health through coordinating plant and rhizosphere microbiome interaction.

Dynamic root microbiome sustains soybean productivity under unbalanced fertilization.

Root-associated microbiomes contribute to plant growth and health, and are dynamically affected by plant development and changes in the soil environment. However, how different fertilizer regimes affect quantitative changes in microbial assembly to effect plant growth remains obscure. Here, we explore the temporal dynamics of the root-associated bacteria of soybean using quantitative microbiome profiling (QMP) to examine its response to unbalanced fertilizer treatments (i.e., lacking either N, P or K) and its role in sustaining plant growth after four decades of unbalanced fertilization. We show that the root-associated bacteria exhibit strong succession during plant development, and bacterial loads largely increase at later stages, particularly for Bacteroidetes. Unbalanced fertilization has a significant effect on the assembly of the soybean rhizosphere bacteria, and in the absence of N fertilizer the bacterial community diverges from that of fertilized plants, while lacking P fertilizer impedes the total load and turnover of rhizosphere bacteria. Importantly, a SynCom derived from the low-nitrogen-enriched cluster is capable of stimulating plant growth, corresponding with the stabilized soybean productivity in the absence of N fertilizer. These findings provide new insights in the quantitative dynamics of the root-associated microbiome and highlight a key ecological cluster with prospects for sustainable agricultural management.

miR-665-Mediated Regulation of AHCYL2 and BVES Genes in Recurrent Implantation Failure.

The primary goal of this investigation was to identify mRNA targets affected by dysregulated miRNAs in RIF. This was accomplished by comprehensively analyzing mRNA and miRNA expression profiles in two groups: female subjects with normal reproductive function (control, n = 5) and female subjects experiencing recurrent implantation failure (RIF, n = 5). We conducted transcriptome sequencing and small RNA sequencing on endometrial tissue samples from these cohorts. Subsequently, we validated a selection of intriguing findings using real-time PCR with samples from the same cohort. In total, our analysis revealed that 929 mRNAs exhibited differential expression patterns between the control and RIF patient groups. Notably, our investigation confirmed the significant involvement of dysregulated genes in the context of RIF. Furthermore, we uncovered promising correlation patterns within these mRNA/miRNA pairs. Functional categorization of these miRNA/mRNA pairs highlighted that the differentially expressed genes were predominantly associated with processes such as angiogenesis and cell adhesion. We identified new target genes that are regulated by miR-665, including Blood Vessel Epicardial Substance (BVES) and Adenosylhomocysteinase like 2 (AHCYL2). Our findings suggest that abnormal regulation of genes involved in angiogenesis and cell adhesion, including BVES and AHCYL2, contributes to the endometrial dysfunction observed in women with recurrent implantation failure (RIF) compared to healthy women.

Deep Potential Molecular Dynamics Study of Propane Oxidative Dehydrogenation.

Oxidative dehydrogenation (ODH) of light alkanes is a key process in the oxidative conversion of alkanes to alkenes, oxygenated hydrocarbons, and COx (x = 1,2). Understanding the underlying mechanisms extensively is crucial to keep the ODH under control for target products, e.g., alkenes rather than COx, with minimal energy consumption, e.g., during the alkene production or maximal energy release, e.g., during combustion. In this work, deep potential (DP), a neural network atomic potential developed in recent years, was employed to conduct large-scale accurate reactive dynamic simulations. The model was trained on a sufficient data set obtained at the density functional theory level. The intricate reaction network was elucidated and organized in the form of a hierarchical network to demonstrate the key features of the ODH mechanisms, including the activation of propane and oxygen, the influence of propyl reaction pathways on the propene selectivity, and the role of rapid H2O2 decomposition for sustainable and efficient ODH reactions. The results indicate the more complex reaction mechanism of propane ODH than that of ethane ODH and are expected to provide insights in the ODH catalyst optimization. In addition, this work represents the first application of deep potential in the ODH mechanistic study and demonstrates the ample advantages of DP in the study of mechanism and dynamics of complex systems.

Boundary-Rich Carbon-Based Electrocatalysts with Manganese(II)-Coordinated Active Environment for Selective Synthesis of Hydrogen Peroxide.

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2 O2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H2 O2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2 O2 productivity up to 15.1 mol gcat -1 h-1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H2 O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O2 ) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2 . These merits together ensure the efficient formation of H2 O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

Clamparene: Synthesis, Structure, and Its Application in Spontaneous Formation of 3D Porous Crystals.

Macrocyclic arenes have emerged as pivotal scaffolds in supramolecular chemistry. Despite their significant contributions to molecular recognition and diverse applications, challenges persist in the development of macrocyclic arene-based crystalline materials, particularly in achieving porosity and addressing limitations in adsorption efficiency resulting from the small cavity sizes of existing macrocyclic arenes. In this study, we present the design and synthesis of a novel macrocyclic arene, clamparene (CLP), featuring a rigid backbone, easy synthesis, and a sizable cavity. CLP self-assembles into one-dimensional sub-nanotubes that further organize into a three-dimensional porous framework in the solid state. The crystalline solid of CLP exhibits potential as a porous crystalline adsorbent for various benzene-based contaminants with rapid adsorption kinetics, large uptake amounts, and good recyclability.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

Oleanolic acid derivative alleviates cardiac fibrosis through inhibiting PTP1B activity and regulating AMPK/TGF-ß/Smads pathway.

Cardiac fibrosis (CF) in response to persistent exogenous stimuli or myocardial injury results in cardiovascular diseases (CVDs). Protein tyrosine phosphatase 1B (PTP1B) can promote collagen deposition through regulating AMPK/TGF-ß/Smads signaling pathway, and PTP1B knockout improves cardiac dysfunction against overload-induced heart failure. Oleanolic acid (OA) has been proven to be an inhibitor of PTP1B, and its anti-cardiac remodeling effects have been validated in different mouse models. To improve the bioactivity of OA and to clarify whether OA derivatives with stronger inhibition of PTP1B activity have greater prevention of cardiac remodeling than OA, four new OA derivatives were synthesized and among them, we found that compound B had better effects than OA in inhibiting cardiac fibrosis both in vivo in the isoproterenol (ISO)-induced mouse cardiac fibrosis and in vitro in the TGF-ß/ISO-induced 3T3 cells. Combining with the results of molecular docking, surface plasmon resonance and PTP1B activity assay, we reported that OA and compound B directly bound to PTP1B and inhibited its activity, and that compound B showed comparable binding capability but stronger inhibitory effect on PTP1B activity than OA. Moreover, compound B presented much greater effects on AMPK activation and TGF-ß/Smads inhibition than OA. Taken together, OA derivative compound B more significantly alleviated cardiac fibrosis than OA through much greater inhibition of PTP1B activity and thus much stronger regulation of AMPK/TGF-ß/Smads signaling pathway.

Hydrogen Spillover-Driven Dynamic Evolution and Migration of Iron Oxide for Structure Regulation of Versatile Magnetic Nanocatalysts.

Magnetic nanocatalysts with properties of easy recovery, induced heating, or magnetic levitation play a crucial role in advancing intelligent techniques. Herein, we report a method for the synthesis of versatile core-shell-type magnetic nanocatalysts through "noncontact" hydrogen spillover-driven reduction and migration of iron oxide with the assistance of Pd. In situ analysis techniques were applied to visualize the dynamic evolution of the magnetic nanocatalysts. Pd facilitates the dissociation of hydrogen molecules into activated H*, which then spills and thus drives the iron oxide reduction, gradual outward split, and migration through the carbonaceous shell. By controlling the evolution stage, nanocatalysts having diverse architectures including core-shell, split core-shell, or hollow type, each featuring Pd or PdFe loaded on the carbon shell, can be obtained. As a showcase, a magnetic nanocatalyst (Pd-loaded split core-shell) can hydrogenate crotonaldehyde to butanal (26 624 h-1 in TOF, ∼100% selectivity), outperforming reported Pd-based catalysts. This is due to the synergy of the enhanced local magnetothermal effect and the preferential adsorption of -C═C on Pd with a small d bandwidth. Another catalyst (PdFe-loaded split core-shell) also delivers a robust performance in phenylacetylene semihydrogenation (100% conversion, 97.5% selectivity) as PdFe may inhibit the overhydrogenation of -C═C. Importantly, not only Pd, other noble metals (e.g., Pt, Ru, and Au) also showed a similar property, revealing a general rule that hydrogen spillover drives the dynamic reduction, splitting, and migration of encapsulated nanosized iron oxide, resulting in diverse structures. This study would offer a structure-controllable fabrication of high-performance magnetic nanocatalysts for various applications.