Nitrogen fixation is one of the most important issues but a long-standing challenge in chemistry. Here, we propose FeN3-embedded graphene as the catalyst for nitrogen fixation from first-principles calculations. Results show that in view of the chemical coordination, the FeN3 center is highly spin-polarized with a localized magnetic moment substantially to promote N2 adsorption and activate its inert N-N triple bond. The synergy between the graphene and FeN3 equips the system with novel features for the catalytic conversion of the activated N2 into NH3 via a six-proton and six-electron process, following three possible reaction pathways at room temperature. Our findings provide a rational paradigm for catalytic nitrogen fixation that would be conducive to ammonia production.

As a phenotypically plastic cellular population, macrophages change their physiology in response to environmental signals. Emerging evidence suggests that macrophages are capable of tightly coordinating their metabolic programs to adjust their immunological and bioenergetic functional properties, as needed. Upon mitogenic stimulation, quiescent macrophages enter the cell cycle, increasing their bioenergetic and biosynthetic activity to meet the demands of cell growth. Proinflammatory stimulation, however, suppresses cell proliferation, while maintaining a heightened metabolic activity imposed by the production of bactericidal factors. Here, we report that the mitogenic stimulus, colony-stimulating factor 1 (CSF-1), engages a myelocytomatosis viral oncogen (Myc)-dependent transcriptional program that is responsible for cell cycle entry and the up-regulation of glucose and glutamine catabolism in bone marrow-derived macrophages (BMDMs). However, the proinflammatory stimulus, lipopolysaccharide (LPS), suppresses Myc expression and cell proliferation and engages a hypoxia-inducible factor alpha (HIF1α)-dependent transcriptional program that is responsible for heightened glycolysis. The acute deletion of Myc or HIF1α selectively impaired the CSF-1-or LPS-driven metabolic activities in BMDM, respectively. Finally, inhibition of glycolysis by 2-deoxyglucose (2-DG) or genetic deletion of HIF1α suppressed LPS-induced inflammation in vivo. Our studies indicate that a switch from a Myc-dependent to a HIF1α-dependent transcriptional program may regulate the robust bioenergetic support for an inflammatory response, while sparing Myc-dependent proliferation.T he cells of the immune system are constantly exposed to environmental challenges and are capable of tailoring their metabolic programs to meet distinct physiological needs. Macrophages, like other immune cells, rapidly change their physiology in response to various environmental cues. Macrophages undergo proliferation in response to mitogenic stimuli, such as colony-stimulating factor 1 (CSF-1) [also known as macrophage CSF (M-CSF)], and this cellular turnover is essential for macrophage homeostasis and may occur in mature macrophages, bypassing the need for self-renewing progenitors (1, 2). Proliferating macrophages consume considerable amounts of energy and require de novo synthesis of macromolecules to support their growth and proliferation (3-6). Therefore, macrophages must coordinately regulate metabolic programs to meet their bioenergetic and biosynthetic demand during proliferation. Despite the emerging view that extracellular signaling events dictate cell growth, proliferation, and death, in part by modulating metabolic activities in cancer cells and T lymphocytes, the precise mechanisms and crucial players of reprogramming metabolism during macrophage proliferation are incompletely understood.Upon encountering an invading microorganism, the bioenergetic potential in macrophages quickly shifts away from fulfilling the needs of cell proliferation to mount a robust...

Reactive oxygen species (ROS) serve as mediators of signal transduction. However, mechanisms of how ROS influence the target molecules to elicit signaling event have not been defined. Our laboratory recently accumulated evidence for the role of protein carbonylation in the mechanism of ROS signaling. This concept originated from experiments in which pulmonary artery smooth muscle cells were treated with endothelin-1 to understand the mechanism of cell growth. Endothelin-1 was found to promote protein carbonylation in an endothelin receptor- and Fenton reaction-dependent manner. Mass spectrometry identified proteins that are carbonylated in response to endothelin-1, including annexin A1. Our experiments generated a hypothesis that endothelin-1-mediated carbonylation and subsequent degradation of annexin A1 promote cell growth. This mechanism was found also to occur in response to other signaling activators such as serotonin and platelet-derived growth factor in smooth muscle cells of pulmonary circulation, systemic circulation, and the airway, as well as in cardiac muscle cells, suggesting the universal role of this pathway. We also discovered a process of decarbonylation that defines transient kinetics of carbonylation signals in certain conditions. We propose that protein carbonylation and decarbonylation serve as a mechanism of signal transduction.

Single atom catalysts (SACs) with the maximized metal atom efficiency have sparked great attention. However, it is challenging to obtain SACs with high metal loading, high catalytic activity, and good stability. Herein, we demonstrate a new strategy to develop a highly active and stable Ag single atom in carbon nitride (Ag‐N2C2/CN) catalyst with a unique coordination. The Ag atomic dispersion and Ag‐N2C2 configuration have been identified by aberration‐correction high‐angle‐annular‐dark‐field scanning transmission electron microscopy (AC‐HAADF‐STEM) and extended X‐ray absorption. Experiments and DFT calculations further verify that Ag‐N2C2 can reduce the H2 evolution barrier, expand the light absorption range, and improve the charge transfer of CN. As a result, the Ag‐N2C2/CN catalyst exhibits much better H2 evolution activity than the N‐coordinated Ag single atom in CN (Ag‐N4/CN), and is even superior to the Pt nanoparticle‐loaded CN (PtNP/CN). This work provides a new idea for the design and synthesis of SACs with novel configurations and excellent catalytic activity and durability.

Cancer stem cells (CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets.

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Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate–cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells.