Abstract
Tuning metal–support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, ...the understanding of the structure–activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal–support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure–activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt–H/Pt–OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.
Here an excellent trimodality imaging‐guided synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) is proposed. To this end, a mixed‐metal Cu/Zn‐metal‐organic ...framework (MOF) is first assembled at room temperature on a nano‐scale. Interestingly, heating the MOF results in a Cu+/2+‐coexisting hollow porous structure. Subsequent heating treatment is used to integrate Mn2+ and MnO2 in the presence of manganese(II) acetylacetonate. The hollow composite achieves efficient loading of a photosensitizer, indocyanine green (ICG). Under laser irradiation, the aggregated ICG achieves photothermal imaging and PTT. Once released in the tumor site, ICG exhibits fluorescence imaging and PDT capacity. Cu+/Mn2+ ions perform Fenton‐like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Cu2+/MnO2 scavenge glutathione to improve the reactive oxygen species‐based therapy, while the formed Mn2+ ions enable “turn on” magnetic resonance imaging. Significantly, O2 is produced from the catalytic decomposition of endogenous H2O2 to improve ICG‐mediated PDT. Moreover, photothermal‐induced local hyperthermia accelerates •OH generation to enhance CDT. This synergistic drug‐free antitumor strategy realizes high treatment efficacy and low side effects on normal tissues. Thus, this mixed‐metal MOF is an efficient strategy to realize hollow structures for multi‐function integration to improve therapeutic capacity.
A mixed‐metal metal‐organic framework strategy is proposed to form a hollow structure, integrating mixed‐metals with mixed‐valences, and loading indocyanine green. The composite enables photothermal/magnetic resonance/fluorescence imaging‐guided photothermal therapy, photodynamic therapy, and chemodynamic therapy. High therapeutic efficiency and negligible side effects are realized as non‐drug treatment.
Appropriate autophagy has protective effects on ischemic nerve tissue, while excessive autophagy may cause cell death. The inflammatory response plays an important role in the survival of nerve cells ...and the recovery of neural tissue after ischemia. Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke. This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows. (1) Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR, the AMPK pathway, and inhibition of inflammasome activation. (2) Activation of inflammation triggers the formation of autophagosomes, and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1. Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK, reducing the flux and autophagy level, thereby inducing inflammatory activity. (3) By blocking the activation of autophagy, the activation of inflammasomes can alleviate cerebral ischemic injury. Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway, which is beneficial to the recovery of neural tissue after ischemia. Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway. These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
A data movie of stochastic optical localization nanoscopy contains spatial and temporal correlations, both providing information of emitter locations. The majority of localization algorithms in the ...literature estimate emitter locations by frame-by-frame localization (FFL), which exploit only the spatial correlation and leave the temporal correlation into the FFL nanoscopy images. The temporal correlation contained in the FFL images, if exploited, can improve the localization accuracy and the image quality. In this paper, we analyze the properties of the FFL images in terms of root mean square minimum distance (RMSMD) and root mean square error (RMSE). It is shown that RMSMD and RMSE can be potentially reduced by a maximum fold equal to the square root of the average number of activations per emitter. Analyzed and revealed are also several statistical properties of RMSMD and RMSE and their relationship with respect to a large number of data frames, bias and variance of localization errors, small localization errors, sample drift, and the worst FFL image. Numerical examples are taken and the results confirm the prediction of analysis. The ideas about how to develop an algorithm to exploit the temporal correlation of FFL images are also briefly discussed. The results suggest development of two kinds of localization algorithms: the algorithms that can exploit the temporal correlation of FFL images and the unbiased localization algorithms.
Aging is the progressive decline or loss of function at the cellular, tissue, and organismal levels that ultimately leads to death. A number of external and internal factors, including diet, ...exercise, metabolic dysfunction, genome instability, and epigenetic imbalance, affect the lifespan of an organism. These aging factors regulate transcriptome changes related to the aging process through chromatin remodeling. Many epigenetic regulators, such as histone modification, histone variants, and ATP-dependent chromatin remodeling factors, play roles in chromatin reorganization. The key to understanding the role of gene regulatory networks in aging lies in characterizing the epigenetic regulators responsible for reorganizing and potentiating particular chromatin structures. This review covers epigenetic studies on aging, discusses the impact of epigenetic modifications on gene expression, and provides future directions in this area.
Sensitivity, selectivity, visible detection, and rapid response are the main concerns for an analytical method. Herein, we reported a metal–organic framework (MOF)-based ratiometric fluorescence ...detection strategy for hypochlorous acid (HClO). The MOF was prepared with dual ligands, 2-aminoterephthalic acid (BDC-NH2) and dipicolinic acid (DPA) and Eu3+ ions as a metal node, denoted as Eu-BDC-NH2/DPA. The dual-ligand strategy realized the dual emission for ratiometric sensing and visual detection, adjusted the size and morphology of MOFs to obtain a good dispersion for a rapid response, and provided an amino group for the special recognition of HClO. Thus, the MOF exhibited a dual emission derived from BDC–NH2 and Eu3+ ions at 433 and 621 nm, respectively, under a single excitation at 270 nm. A hydrogen bond forms between an −NH2 group and HClO to weaken the blue fluorescence at 433 nm, while the antenna effect emission from Eu3+ ions kept stable, so ratiometric sensing was realized with an easy-to-differentiate color change for visible detection. The ratiometric sensing showed a self-calibration effect and reduced the background. Thus, the high sensitivity, visual detection, low detection limit (37 nM), and short response time (within 20 s) for the detection of HClO were realized with the MOF as a probe. The analysis of real samples demonstrated the practical application of the MOF for HClO. The introduction of mixed ligands is an effective strategy to regulate the emission behaviors of MOFs for the improved analytical performance.
Micro/Nano robots have shown enormous potential for diverse biomedical applications, such as targeted delivery, in vivo biosensing, minimally invasive surgery and cell manipulation through extending ...their area of operation to various previously inaccessible locations. The motion of these small-scale robots can be either self–propelled or remotely controlled by some external power sources. However, in order to use them for biomedical applications, optimization of biocompatible propulsion and precise controllability are highly desirable. In this article, the recent progress about the biocompatible propulsion (e.g. self-propulsion, external stimuli based propulsion and bio-hybrid propulsion) techniques for these micro/nano robotic devices are summarized along with their applications, with a special focus on the advantages and disadvantages of different propulsion techniques. The current challenges and future perspectives of these small-scale devices are discussed in the final section.
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This review paper discusses:•The enormous potential of micro/nano robotics for advancing biomedical applications.•The latest development of the biocompatible propulsion techniques.•The future research needed to prompt the widespread adoption of micro/nano robotics in the biomedical sector.
Inorganic–organic hybrid perovskites are a new family of solar cell materials, which have recently been used to make solar cells with efficiency approaching 20%. Here, we report the unique defect ...chemistry of the prototype material, CH3NH3PbI3, based on first-principles calculation. We found that both the Pb cations and I anions in this material exhibit strong covalency as characterized by the formation of Pb dimers and I trimers with strong covalent bonds at some of the intrinsic defects. The Pb dimers and I trimers are only stabilized in a particular charge state with significantly lowered energy, which leads to deep charge-state transition levels within the band gap, in contradiction to a recent proposal that this system has only shallow intrinsic defects. Our results show that, in order to prevent the deep-level defects from being effective recombination centers, the equilibrium carrier concentrations should be controlled so that the Fermi energy is about 0.3 eV away from the band edges. Beyond this range, according to a Shockley–Read–Hall analysis, the non-equilibrium carrier lifetime will be strongly affected by the concentration of I vacancies and the anti-site defects with I occupying a CH3NH3 site.
E3 ubiquitin ligases are a large family of proteins that are engaged in the regulation of the turnover and activity of many target proteins. Together with ubiquitinactivating enzyme El and ...ubiquitin-conjugating enzyme E2, E3 ubiquitin ligases catalyze the ubiquitination of a variety of biologically significant protein substrates for targeted degradation through the 26S proteasome, as well as for nonproteolytic regulation of their functions or subcellular localizations. E3 ubiquitin ligases, therefore, play an essential role in the regulation of many biologic processes. Increasing amounts of evidence strongly suggest that the abnormal regulation of some E3 ligases is involved in cancer development. Furthermore, some E3 ubiquitin ligases are frequently overexpressed in human cancers, which correlates well with increased chemoresistance and poor clinic prognosis. In this review, E3 ubiquitin ligases (such as murine double minute 2, inhibitor of apoptosis protein, and Skpi-Cullin-F-box protein) will be evaluated as potential cancer drug targets and prognostic biomarkers. Extensive study in this field would lead to a better understanding of the molecular mechanism by which E3 ligases regulate cellular processes and of how their deregulations contribute to carcinogenesis. This would eventually lead to the development of a novel class of anticancer drugs targeting specific E3 ubiquitin ligases, as well as the development of sensitive biomarkers for cancer treatment, diagnosis, and prognosis.
Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The ...best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins. Recently, increasing pieces of experimental evidence strongly indicate that the process of protein neddylation modification is elevated in multiple human cancers, providing sound rationale for its targeting as an attractive anticancer therapeutic strategy. Indeed, neddylation inactivation by MLN4924 (also known as pevonedistat), a small molecule inhibitor of E1 NEDD8-activating enzyme currently in phase I/II clinical trials, exerts significant anticancer effects by inducing cell cycle arrest, apoptosis, senescence and autophagy in a cell-type and context dependent manner. Here, we summarize the latest progresses in the field with a major focus on preclinical studies in validation of neddylation modification as a promising anticancer target.
•Neddylation is one type of post-translational modifications that alters protein function.•Several components that catalyze neddylation modification are over-expressed in multiple human cancers.•Small molecular inhibitor of neddylation modification suppresses cancer cell growth via multiple mechanisms.•Neddylation modification has been validated as a promising anti-cancer target.
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