Highlights d circRNAs are globally degraded by activated RNase L upon viral infection d Many circRNAs tend to form 16-26 bp duplexes and act as endogenous PKR inhibitors d The RNase L-mediated circRNA degradation is required for PKR activation d circRNA reduction and aberrant PKR activation are found in autoimmune disease SLE
The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor‐specific therapy, here a novel concept of photothermal‐enhanced sequential nanocatalytic therapy in both NIR‐I and NIR‐II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (•OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H2O2 by glucose oxidase (GOD), an Fe3O4/GOD‐functionalized polypyrrole (PPy)‐based composite nanocatalyst is constructed to achieve diagnostic imaging‐guided, photothermal‐enhanced, and TME‐specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H2O2 level, and the integrated Fe3O4 component then catalyzes H2O2 into highly toxic •OH to efficiently induce cancer‐cell death. Importantly, the high photothermal‐conversion efficiency (66.4% in NIR‐II biowindow) of the PPy component elevates the local tumor temperature in both NIR‐I and NIR‐II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H2O2 for enhancing the nanocatalytic‐therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.
The explosion of emerging high-performance 2D MXenes in theranostic nanomedicine is still at the preliminary stage. Despite tremendous efforts devoted to photonic tumor hyperthermia, current photothermal-conversion nanoagents still suffer from critical issues preventing further clinical translation such as low biodegradability. Here, for the first time, the construction of novel 2D molybdenum carbide (Mo 2 C) MXenes for photonic tumor hyperthermia is reported. The structure of both bulk Mo 2 Ga 2 C ceramic and Mo 2 C MXene is fully revealed. Especially, computational simulation, as a novel strategy and a powerful tool for photonic-performance prediction, is employed to reveal that Mo 2 C MXene is featured with intense near-infrared (NIR) absorption, covering the first and the second biological transparency window (NIR I and II). After further surface engineering with polyvinyl alcohol (PVA), Mo 2 C-PVA nanoflakes exhibit high biocompatibility and fast degradability. Importantly, it is experimentally corroborated that Mo 2 C-PVA nanoflakes possess intriguing broad absorption band spanning NIR in both the I and II regions, and desirable photothermal-conversion efficiency (24.5% for NIR I and 43.3% for NIR II). This study not only broadens the nanomedical applications of MXene by fabricating novel material members (Mo 2 C), but also provides the paradigm of inorganic multifunctional biomedical nanoplatform with desirable biodegradability and high therapeutic performance.
Atmospheric carbon dioxide (CO2) is assimilated by the most abundant but sluggish enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Here we show that acetylation of lysine residues of the Rubisco large subunit (RbcL), including Lys201 and Lys334 in the active sites, may be an important mechanism in the regulation of Rubisco activities. It is well known that Lys201 reacts with CO2 for carbamylation, a prerequisite for both carboxylase and oxygenase activities of Rubisco, and Lys334 contacts with ribulose-1,5-bisphosphate (RuBP). The acetylation level of RbcL in plants is lower during the day and higher at night, inversely correlating with the Rubisco carboxylation activity. A search of the chloroplast proteome database did not reveal a canonical acetyltransferase; instead, we found that a plant-derived metabolite, 7-acetoxy-4-methylcoumarin (AMC), can non-enzymatically acetylate both native Rubisco and synthesized RbcL peptides spanning Lys334 or Lys201. Furthermore, lysine residues were modified by synthesized 4-methylumbelliferone esters with different electro- and stereo-substitutes, resulting in varied Rubisco activities. 1-Chloroethyl 4-methylcoumarin-7-yl carbonate (ClMC) could transfer the chloroethyl carbamate group to lysine residues of RbcL and completely inactivate Rubisco, whereas bis(4-methylcoumarin-7-yl) carbonate (BMC) improved Rubisco activity through increasing the level of Lys201 carbamylation. Our findings indicate that RbcL acetylation negatively regulates Rubisco activity, and metabolic derivatives can be designed to dissect and improve CO2 fixation efficiency of plants through lysine modification.
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