Neutrophil elastase:From mechanisms to therapeutic potential

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Ultrathin two-dimensional medium-entropy oxide as a highly efficient and stable electrocatalyst for oxygen evolution reaction

Medium-entropy oxides(MEOs)with broad compositional tunability and entropy-driven structural stability,are receiving booming attention as a promising candidate for oxygen evolution reaction(OER)electrocatalysts.Meanwhile,ultrathin two-dimensional(2D)nanostructure offers extremely large specific surface area and is therefore considered to be an ideal catalyst structure.However,it remains a grant challenge to synthesize ultrathin 2D MEOs due to distinct nucleation and growth kinetics of constituent multimetallic elements in 2D anisotropic systems.In this work,an ultrathin 2D MEO(MnFeCoNi)O was successfully synthesized by a facile and low-temperature ionic layer epitaxy method.Benefiting from multi-metal synergistic effects within ultrathin 2D nanostructure,this 2D MEO(MnFeCoNi)O revealed excellent OER electrocatalytic performance with a quite low overpotential of 117 mV at 10 mA·cm^(-2) and an impressive stability for 120 h continuous operation with only 6.9%decay.Especially,the extremely high mass activity(5584.3 A·g^(-1))was three orders of magnitude higher than benchmark RuO_(2)(3.4 A·g^(-1))at the same overpotential of 117 mV.This work opens up a new avenue for developing highly efficient and stable electrocatalysts by creating 2D nanostructured MEOs.

Metal matrix nanocomposites in tribology: Manufacturing, performance, and mechanisms

Metal matrix nanocomposites(MMNCs)become irreplaceable in tribology industries,due to their supreme mechanical properties and satisfactory tribological behavior.However,due to the dual complexity of MMNC systems and tribological process,the anti-friction and anti-wear mechanisms are unclear,and the subsequent tribological performance prediction and design of MMNCs are not easily possible:A critical up-to-date review is needed for MMNCs in tribology.This review systematically summarized the fabrication,manufacturing,and processing techniques for high-quality MMNC bulk and surface coating materials in tribology.Then,important factors determining the tribological performance(mainly anti-friction evaluation by the coefficient of friction(CoF)and anti-wear assessment with wear rate)in MMNCs have been investigated thoroughly,and the correlations have been analyzed to reveal their potential coupling/synergetic roles of tuning tribological behavior of MMNCs.Most importantly,this review combined the classical metal/alloy friction and wear theories and adapted them to give a(semi-)quantitative description of the detailed mechanisms of improved anti-friction and anti-wear performance in MMNCs.To guarantee the universal applications of these mechanisms,their links with the analyzed influencing factors(e.g.,loading forces)and characteristic features like tribo-film have been clarified.This approach forms a solid basis for understanding,predicting,and engineering MMNCs’tribological behavior,instead of pure phenomenology and experimental observation.Later,the pathway to achieve a broader application for MMNCs in tribo-related fields like smart materials,biomedical devices,energy storage,and electronics has been concisely discussed,with the focus on the potential development of modeling,experimental,and theoretical techniques in MMNCs’tribological processes.In general,this review tries to elucidate the complex tribo-performances of MMNCs in a fundamentally universal yet straightforward way,and the discussion and summary in this review for the tribological performance in MMNCs could become a useful supplementary to and an insightful guidance for the current MMNC tribology study,research,and engineering innovations.

5-Formylcytosine and 5-Carboxylcytosine Significantly Reduce the Catalytic Activity of Hhal DNA Methyltransferase

DNA methylation is an essential epigenetic modification, and found to be dynamically changed due to the ob- servation of active DNA demethylation. During active demethylation, 5-methylcytosine （5mC） was oxidized step- wise by ten-eleven translocation （TET） enzymes into 5-hydroxymethylcytosine （5hmc）, 5-formylcytosine （5fC）, and 5-carboxylcytosine （5caC）. Then, the subsequent excision of 5fC and 5caC combined with base excision repair further restored cytosine, which completes the demethylation process. Here, we report that 5-formylcytosine and 5-carboxylcytosine significantly reduce the activity of HhaI DNA methyltransferase to methylate target cytosines when present on the hemi-modified sequence of the complementary DNA. This finding demonstrates that 5fC and 5caC function as more than intermediates for active DNA demethylation.