Synergistic Al-Al Dual-Atomic Site for Efficient Artificial Nitrogen Fixation.

Synthesis of ammonia by electrochemical nitrogen reduction reaction (NRR) is a promising alternative to the Haber-Bosch process. However, it is commonly obstructed by the high activation energy. Here, we report the design and synthesis of an Al-Al bonded dual atomic catalyst stabilized within an amorphous nitrogen-doped porous carbon matrix (Al2NC) with high NRR performance. The dual atomic Al2-sites act synergistically to catalyze the complex multiple steps of NRR through adsorption and activation, enhancing the proton-coupled electron transfer. This Al2NC catalyst exhibits a high Faradaic efficiency of 16.56±0.3 % with a yield rate of 29.22±1.2 µg h-1 mgcat -1. The dual atomic Al2NC catalyst shows long-term repeatable, and stable NRR performance. This work presents an insight into the identification of synergistic dual atomic catalytic site and mechanistic pathway for the electrochemical conversion of N2 to NH3.

Comparative Toxicological Effects of Perfluorooctane Sulfonate and Its Alternative 6:2 Chlorinated Polyfluorinated Ether Sulfonate on Earthworms.

High levels of 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), which is a substitute for perfluorooctane sulfonate (PFOS), are detected in various environmental matrices, wildlife, and humans. Chlorinated polyfluorinated ether sulfonate has received increased attention due to its potential risk to ecosystems. However, its toxicity in the soil organisms remains unclear. In the present study, a comparative investigation was conducted on the toxicities of 6:2 Chlorinated polyfluorinated ether sulfonate (F-53B) and PFOS to the earthworm Eisenia. fetida. F-53B was significantly more acutely toxic to earthworms than PFOS, with median lethal concentrations of 1.43 and 1.83 mmol/kg dry soil (~816 and 984 mg/kg dry soil), respectively. Although both F-53B and PFOS, at 0.4 mmol/kg dry soil (=228 and 215 mg/kg dry soil) caused oxidative stress in earthworms, as evidenced by increased superoxide dismutase, peroxidase, and catalase activities as well as malondialdehyde level, the stress caused by F-53B was higher than that caused by PFOS. In transcriptomic and metabolomic studies, negative effects of PFOS and F-53B were observed on several metabolic processes in earthworms, including protein digestion and amino acid absorption, lipid metabolism, and the immune response. Compared with PFOS, F-53B exhibited a weaker disruption of lipid metabolism, comparable potency for toxicity to the immune response, and a stronger potency in extracellular matrix destruction along with apoptosis and ferroptosis induction. Hence, our data suggest that F-53B is more toxic than PFOS to earthworms. The findings provide some new insights into the potential toxicity of F-53B to soil organisms. Environ Toxicol Chem 2024;43:170-181. © 2023 SETAC.

Selectivity Control in the Direct CO Esterification over Pd@UiO-66: The Pd Location Matters.

The selectivity control of Pd nanoparticles (NPs) in the direct CO esterification with methyl nitrite toward dimethyl oxalate (DMO) or dimethyl carbonate (DMC) remains a grand challenge. Herein, Pd NPs are incorporated into isoreticular metal-organic frameworks (MOFs), namely UiO-66-X (X=-H, -NO2 , -NH2 ), affording Pd@UiO-66-X, which unexpectedly exhibit high selectivity (up to 99 %) to DMC and regulated activity in the direct CO esterification. In sharp contrast, the Pd NPs supported on the MOF, yielding Pd/UiO-66, displays high selectivity (89 %) to DMO as always reported with Pd NPs. Both experimental and DFT calculation results prove that the Pd location relative to UiO-66 gives rise to discriminated microenvironment of different amounts of interface between Zr-oxo clusters and Pd NPs in Pd@UiO-66 and Pd/UiO-66, resulting in their distinctly different selectivity. This is an unprecedented finding on the production of DMC by Pd NPs, which was previously achieved by Pd(II) only, in the direct CO esterification.

A Sulfur-Tolerant MOF-Based Single-Atom Fe Catalyst for Efficient Oxidation of NO and Hg0.

Catalytic oxidation of NO and Hg0 is a crucial step to eliminate multiple pollutants from emissions from coal-fired power plants. However, traditional catalysts exhibit low catalytic activity and poor sulfur resistance due to low activation ability and poor adsorption selectivity. Herein, a single-atom Fe decorated N-doped carbon catalyst (Fe1 -N4 -C), with abundant Fe1 -N4 sites, based on a Fe-doped metal-organic framework is developed to oxidize NO and Hg0 . The results demonstrate that the Fe1 -N4 -C has ultrahigh catalytic activity for oxidizing NO and Hg0 at low and room temperature. More importantly, Fe1 -N4 -C exhibits robust sulfur resistance as it preferably adsorbs reactants over sulfur oxides, which has never been achieved before with traditional catalysts. Furthermore, SO2 boosts the catalytic oxidation of NO over Fe1 -N4 -C through accelerating the circulation of active sites. Density functional theory calculations reveal that the Fe1 -N4 active sites result in a low energy barrier and high adsorption selectivity, providing detailed molecular-level understanding for its excellent catalytic performance. This is the first report on NO and Hg0 oxidation over single-atom catalysts with strong sulfur tolerance. The outcomes demonstrate that single-atom catalysts are promising candidates for catalytic oxidation of NO and Hg0 enabling cleaner coal-fired power plant operations.

Exploring the Effects of Ionic Defects on the Stability of CsPbI3 with a Deep Learning Potential.

Inorganic metal halide perovskites, such as CsPbI3 , have recently drawn extensive attention due to their excellent optical properties and high photoelectric efficiencies. However, the structural instability originating from inherent ionic defects leads to a sharp drop in the photoelectric efficiency, which significantly limits their applications in solar cells. The instability induced by ionic defects remains unresolved due to its complicated reaction process. Herein, to explore the effects of ionic defects on stability, we develop a deep learning potential for a CsPbI3 ternary system based upon density functional theory (DFT) calculated data for large-scale molecular dynamics (MD) simulations. By exploring 2.4 million configurations, of which 7,730 structures are used for the training set, the deep learning potential shows an accuracy approaching DFT-level. Furthermore, MD simulations with a 5,000-atom system and a one nanosecond timeframe are performed to explore the effects of bulk and surface defects on the stability of CsPbI3 . This deep learning potential based MD simulation provides solid evidence together with the derived radial distribution functions, simulated diffraction of X-rays, instability temperature, molecular trajectory, and coordination number for revealing the instability mechanism of CsPbI3 . Among bulk defects, Cs defects have the most significant influence on the stability of CsPbI3 with a defect tolerance concentration of 0.32 %, followed by Pb and I defects. With regards to surface defects, Cs defects have the largest impact on the stability of CsPbI3 when the defect concentration is less than 15 %, whereas Pb defects act play a dominant role for defect concentrations exceeding 20 %. Most importantly, this machine-learning-based MD simulation strategy provides a new avenue to explore the ionic defect effects on the stability of perovskite-like materials, laying a theoretical foundation for the design of stable perovskite materials.

Rapamycin facilitates differentiation of regulatory T cells via enhancement of oxidative phosphorylation.

We explored the interplay between energy metabolism and the impact of rapamycin (Rapa) on regulatory T cell (Treg) differentiation. Naïve CD4+ T cells were stimulated under Treg-polarizing conditions with or without Rapa. Rapa promoted Treg induction, as the expression of Foxp3 and Treg phenotypic markers were enhanced. Rapa disrupts glycolysis while favoring mitochondrial metabolism in induced Tregs (iTregs). Metabolic profiling showed reduced glycolytic metabolites in Rapa-treated iTregs, in line with the downregulation of glucose uptake and the expression of glycolytic enzymes. Conversely, Rapa increased the ratios of ATP/ADP and ATP/AMP, the production of mitochondrial ATP, and the expression of ATP5A. Treatment with oxidative phosphorylation inhibitors suppressed Foxp3 expression in Rapa-treated cells. Moreover, Rapa decreased oleic acid and palmitoleic acid levels and increased l-carnitine and acetylcarnitine levels and CPT1A expression in iTregs, indicative of augmented fatty acid oxidation. In conclusion, Rapa induces metabolic reprogramming in Tregs, affecting their differentiation.

TGF-ß1 maintains Foxp3 expression and inhibits glycolysis in natural regulatory T cells via PP2A-mediated suppression of mTOR signaling.

Natural regulatory T cells (nTregs) play a dominant role in maintaining immunological homeostasis and they are known to undergo metabolic reprogramming during immune responses. Transforming growth factor-ß1 (TGF-ß1), an anti-inflammatory cytokine, can promote the induction of regulatory T cells. Here, we investigated the effects of TGF-ß1 on the stability and metabolism of nTregs stimulated in vitro. CD4+CD25+ nTregs were isolated from mouse spleens and stimulated with anti-CD3 and anti-CD28 antibodies plus IL-2 in the presence or absence of TGF-ß1. Exposure to TGF-ß1 induced the activation of STAT5 and sustained the expression of the nTregs transcription factor Foxp3. In addition, TGF-ß1 inhibited glycolysis, as shown by reduced lactate production and diminished expression of Glut1, Hk2, Enolase1, and Hif-1α. nTregs treated with TGF-ß1 exhibited downregulated mTORC1 signaling but enhanced activation of the serine-threonine phosphatase PP2A. Moreover, treat with the PP2A inhibitor okadaic acid disrupted the maintenance of Foxp3 expression by TGF-ß1. Thus, TGF-ß1 serves to maintain Foxp3 expression in cultured nTregs, possibly via PP2A activation and suppression of mTORC1-regulated glycolysis.

Multifaceted protein-protein interaction prediction based on Siamese residual RCNN.

MOTIVATION: Sequence-based protein-protein interaction (PPI) prediction represents a fundamental computational biology problem. To address this problem, extensive research efforts have been made to extract predefined features from the sequences. Based on these features, statistical algorithms are learned to classify the PPIs. However, such explicit features are usually costly to extract, and typically have limited coverage on the PPI information. RESULTS: We present an end-to-end framework, PIPR (Protein-Protein Interaction Prediction Based on Siamese Residual RCNN), for PPI predictions using only the protein sequences. PIPR incorporates a deep residual recurrent convolutional neural network in the Siamese architecture, which leverages both robust local features and contextualized information, which are significant for capturing the mutual influence of proteins sequences. PIPR relieves the data pre-processing efforts that are required by other systems, and generalizes well to different application scenarios. Experimental evaluations show that PIPR outperforms various state-of-the-art systems on the binary PPI prediction problem. Moreover, it shows a promising performance on more challenging problems of interaction type prediction and binding affinity estimation, where existing approaches fall short. AVAILABILITY AND IMPLEMENTATION: The implementation is available at https://github.com/muhaochen/seq_ppi.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

One-pot solvothermal synthesis of reduced graphene oxide-supported uniform PtCo nanocrystals for efficient and robust electrocatalysis.

Pt-based nanocomposites with low Pt utilization and high-activity by incorporating with other transition metals have received significant interest in catalysis. Meanwhile, loading Pt-based catalysts on graphene has great research value for improved stability and dispersity of the catalysts. Herein, a facile l-proline-mediated solvothermal strategy was reported to construct reduced graphene oxide (rGO) supported sheet-like PtCo nanocrystals (Pt78Co22 NCs/rGO) in ethylene glycol (EG). The as-synthesized nanocomposite manifested remarkably improved catalytic properties and chemical stability for oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER), surpassing home-made Pt29Co71 nanoparticles (NPs)/rGO, Pt83Co17 NPs/rGO, Pt52Co48 NPs, commercial Pt/C and Pt black catalysts. These scenarios demonstrated an improved catalytic performances by tailoring the feeding ratio of Pt:Co and introducing rGO as a support. This work provides some new insights to design rGO-supported Pt-based catalysts by engineering the shapes and compositions in practical fuel cells.

HIF-1α protects against oxidative stress by directly targeting mitochondria.

The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates adaptive responses to oxidative stress by nuclear translocation and regulation of gene expression. Mitochondrial changes are critical for the adaptive response to oxidative stress. However, the transcriptional and non-transcriptional mechanisms by which HIF-1α regulates mitochondria in response to oxidative stress are poorly understood. Here, we examined the subcellular localization of HIF-1α in human cells and identified a small fraction of HIF-1α that translocated to the mitochondria after exposure to hypoxia or H2O2 treatment. Moreover, the livers of mice with CCl4-induced fibrosis showed a progressive increase in HIF-1α association with the mitochondria, indicating the clinical relevance of this finding. To probe the function of this HIF-1α population, we ectopically expressed a mitochondrial-targeted form of HIF-1α (mito-HIF-1α). Expression of mito-HIF-1α was sufficient to attenuate apoptosis induced by exposure to hypoxia or H2O2-induced oxidative stress. Moreover, mito-HIF-1α expression reduced the production of reactive oxygen species, the collapse of mitochondrial membrane potential, and the expression of mitochondrial DNA-encoded mRNA in response to hypoxia or H2O2 treatment independently of nuclear pathways. These data suggested that mitochondrial HIF-1α protects against oxidative stress induced-apoptosis independently of its well-known role as a transcription factor.

Uric acid supported one-pot solvothermal fabrication of rhombic-like Pt35Cu65 hollow nanocages for highly efficient and stable electrocatalysis.

High activity and good durability of electrocatalysts are of significance in practical applications of fuel cells. Among them, multi-component metallic hollow nanocages/nanoframes show great potential as advanced catalysts because of their highly open structures, large surface area and good stability. Herein, we report a general uric acid-mediated solvothermal method for shape-controlled synthesis of rhombic-like Pt35Cu65 hollow nanocages (HNCs) with uric acid as co-reductant and co-structure-directing agent. Uric acid and cetyltrimethylammonium chloride (CTAC) played important roles in the hollow cages. The specific architectures showed remarkably enhanced catalytic properties towards glycerol oxidation reaction (GOR), ethylene glycol oxidation reaction (EGOR) and oxygen reduction reaction (ORR) with the enhanced specific activity, outperforming commercial Pt/C (20 wt%). This work provides a new avenue for rational design of novel bimetallic nanocatalysts with enhanced characters in energy storage and conversion.

Facile solvothermal synthesis of Pt71Co29 lamellar nanoflowers as an efficient catalyst for oxygen reduction and methanol oxidation reactions.

The research for highly efficient and stable electrocatalysts in fuel cells has attracted substantial interest. Herein, bimetallic alloyed Pt71Co29 lamellar nanoflowers (LNFs) with abundant active sites were obtained by a one-pot solvothermal method, where cetyltrimethylammonium chloride (CTAC) and 1-nitroso-2-naphthol (1-N-2-N) served as co-structure-directors, while oleylamine (OAm) as the solvent and reducing agent. The fabricated Pt71Co29 LNFs exhibited the higher mass activity (MA, 128.29 mA mg-1) for oxygen reduction reaction (ORR) than those of home-made Pt48Co52 nanodendrites (NDs), Pt79Co21 NDs and commercial Pt black with the values of 39.46, 49.42 and 22.91 mA mg-1, respectively. Meanwhile, the MA (666.23 mA mg-1) and specific activity (SA, 2.51 mA cm-2) of the constructed Pt71Co29 LNFs for methanol oxidation reaction (MOR) are superior than those of Pt48Co52 NDs (213.91 mA mg-1, 1.99 mA cm-2), Pt79Co21 NDs (210.09 mA mg-1, 1.12 mA cm-2) and Pt black (57.03 mA mg-1, 0.25 mA cm-2). Also, the Pt71Co29 LNFs catalyst exhibited the best durable ability relative to the references. This work demonstrates that the developed strategy provides a facile platform for synthesis of high-performance, low-cost and robust catalysts in practical catalysis, energy storage and conversion.

Facile solvothermal fabrication of polypyrrole sheets supported dendritic platinum-cobalt nanoclusters for highly efficient oxygen reduction and ethylene glycol oxidation.

Herein, uniform dendritic PtCo nanoclusters supported on sheet-like polypyrrole (PtCo NCs/PPy) were prepared by a facile one-pot solvothermal method. Cetyltrimethylammonium chloride (CTAC) and pyrrole worked as the capping agent and reductant, respectively, and pyrrole was in-situ polymerized to form PPy sheets under solvothermal conditions. The dendritic PtCo NCs/PPy had the enlarged electrochemically active surface area (EASA, 30.95 m2g-1), and showed the superior catalytic performance and durability towards oxygen reduction reaction (ORR) and ethylene glycol oxidation reaction (EGOR) in comparison with Pt1Co3 nanoparticles (NPs), Pt3Co1 NPs and commercial Pt/C catalysts. This work displays a new strategy for rational design and synthesis of advanced functional nanocomposites as electrocatalysts in fuel cells.

Facile solvothermal fabrication of Pt47Ni53 nanopolyhedrons for greatly boosting electrocatalytic performances for oxygen reduction and hydrogen evolution.

Pt-based bimetallic nanostructures with low content of Pt were considered as one of the attractive nanocatalysts for their high Pt utilization efficiency, remarkable catalytic characters and cost-effectiveness in facilitating the sluggish cathodic reactions in fuel cells. Herein, three-dimensional Pt47Ni53 nanopolyhedrons (NPHs) with abundant active sites were constructed by a facile one-pot solvothermal strategy, in which cytosine and cetyltrimethylammonium chloride (CTAC) worked as the co-structure directing agents. The Pt47Ni53 NPHs were mainly characterized by a series of techniques, showing the high catalytic activity and stability towards oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) in comparison to Pt13Ni87 nanocrystals (NCs), Pt63Ni37 NCs, commercial Pt black and/or Pt/C catalysts. Impressively, the mass activity of Pt47Ni53 NPHs was about 215.80 mA mgPt-1 for ORR, approximately 4-time increase relative to Pt black (49.60 mA mgPt-1). These results demonstrate the promising applications of the synthesized nanocatalysts in energy storage and transformation.

Celastrol mediates Th17 and Treg cell generation via metabolic signaling.

A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol. Initially, we determined that Interleukin (IL)-17 expression by celastrol-treated Th17 was significantly decreased compared with untreated cells; however, the frequency of Foxp3+ cells was increased in celastrol-treated cells. We verified that celastrol inhibited phospho-STAT3 expression in cultured Th17 cells and up-regulated phospho-STAT5 expression in iTreg cells. Furthermore, T cells treated with celastrol were more likely to participate in FAO metabolism instead of glycolysis. Celastrol suppressed the expression of glucose transporter, Glut1, and the rate-limiting enzyme, HK2, in addition to mTOR, HIF-1α, c-Myc and Akt expression in Th17 cells. Conversely, celastrol promoted FAO of lipids by up-regulating CPT1A and AMPKα expression in iTreg cells. Our results suggest that celastrol suppresses Th17 cell induction, while promoting the generation of iTreg cells. We found that celastrol inhibits glycolysis in Th17 cells and promotes FAO by iTreg cells, suggesting that celastrol could mediate the metabolism of Th17 and iTreg cells.

One-pot fabrication of reduced graphene oxide supported dendritic core-shell gold@gold-palladium nanoflowers for glycerol oxidation.

Herein, a one-pot wet-chemical route was used to prepare well-defined dendritic core-shell gold@gold-palladium nanoflowers supported on reduced graphene oxide (Au@AuPd NFs/rGO), using 2, 4-dihydroxypyridine (2, 4-DHP) asa new stabilizer and structure-director. Their morphology, size, composition, and crystal structure were characterized by a set of characterization techniques. Control experiments demonstrated that the molar ratio of the metal precursors and the dosage of 2,4-DHP play essential roles in this synthesis. The growth mechanism of dendritic core-shell Au@AuPd nanoflowers was investigated in details. The synthesized branched architectures exhibited enlarged electrochemically active surface area (ECSA), improved catalytic properties, enhanced stability and durability toward glycerol oxidation in alkaline media when compared to the home-made Au26Pd74 nanocrystals (NCs)/rGO and Au78Pd22 NCs/rGO, along with commercially available Pd/C catalyst.

Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: An analysis of patient perceptions.

OBJECTIVES: This study aimed to identify factors associated with initiation and adherence of osteoporosis medication from a patient perspective. METHODS: A web-based survey was developed based on health behavior theories. Descriptive analyses were conducted for all survey items. Analyses in a structural equation modeling framework were conducted to identify factors associated with treatment initiation and adherence. RESULTS: Five hundred forty-five women completed the questionnaire. A majority were currently receiving medications for osteoporosis (n = 376, 69.0%) and 25.0% of these patients (n = 94) were considered adherent to their treatment. Knowledge was strongly associated with osteoporosis treatment initiation (standard error [SE], 0.58). Greater knowledge of disease was associated with increased likelihood of initiating medication. Medication complexity (SE, 0.49) and perceived susceptibility to fracture and loss of independence (SE, -0.37) were also associated with initiation. Perceived barriers (SE, -0.85) such as inconvenience, lack of efficacy and financial burden were observed to be the greatest obstacle to adherence. The greater the perceived barriers, the less likely patients were to adhere to medication. Patients' perception of self-efficacy (SE, 0.37) also affected adherence. The greater the patient perception of ability to independently manage their medication, the more likely they were to adhere to the medication. CONCLUSIONS: Different factors were found to be associated with initiation and adherence of osteoporosis medication. Patient knowledge of their disease and the perception of barriers were found to be the most influential. Empowering patients with the knowledge to better understand their disease and decreasing the perception of barriers through education initiatives may be effective in improving patient outcomes.

The effects of rapamycin on regulatory T cells: its potential time-dependent role in inducing transplant tolerance.

The immunosuppressive drug rapamycin (RAPA) has been used clinically to prevent graft rejection since 1999 because of its suppressive effects on T cell activation and proliferation. Recently, many studies have suggested that RAPA also has the potential to promote tolerance by driving the expansion of naturally occurring regulatory T (Treg) cells, and facilitating the de novo generation of induced Treg cells, which has aroused great interest in its potential ability to promote tolerance after transplantation. However, its effect on Treg cells remains controversial both in vitro and in vivo. Here, we systematically analyzed data on the effects of RAPA from both clinical and basic studies: (1) To compare its clinical effect with calcineurin inhibitors in transplant recipients, and discuss whether its effects on graft survival correlates with its effects on Treg cells. (2) To analyze the effects of RAPA on Treg cells from animal and in vitro studies, and to investigate whether the effects of RAPA on Treg cells was dependent on dosage and timing. (3) To discuss the mechanisms involved and how they might be applied to induce transplant tolerance.