Inhibition of SIRT1/2 upregulates HSPA5 acetylation and induces pro-survival autophagy via ATF4-DDIT4-mTORC1 axis in human lung cancer cells.

Sirtuins have emerged as a promising novel class of anti-cancer drug targets. Inhibition of SIRT1 and SIRT2 induces apoptosis in cancer cells and they play multifaceted roles in regulating autophagy. In the present study, we found that salermide, a SIRT1/2-specific inhibitor or small interfering RNAs (siRNAs) to block SIRT1/2 expression could induce autophagy in human NSCLC cells. Moreover, SIRT1/2 inhibition increased the expression levels of ATF4 and DDIT4 and downregulated p-RPS6KB1 and p-EIF4EBP1, two downstream molecules of mTORC1. Moreover, ATF4 or DDIT4 knockdown attenuated salermide-induced autophagy, suggesting that SIRT1/2 inhibition induced autophagy through the ATF4-DDIT4-mTORC1 axis. Mechanistically, SIRT1/2 inhibition led to HSPA5 acetylation and dissociation from EIF2AK3, leading to ER stress response and followed by upregulation of ATF4 and DDIT4, triggering autophagy. Silencing of the autophagic gene ATG5 in lung cancer cells resulted in increased apoptotic cell death induced by SIRT1/2 inhibition. Our data show that inhibition of SIRT1/2 induces pro-survival autophagy via acetylation of HSPA5 and subsequent activation of ATF4 and DDIT4 to inhibit the mTOR signaling pathway in NSCLC cells. These findings suggest that combinatorial treatment with SIRT1/2 inhibitors and pharmacological autophagy inhibitors is an effective therapeutic strategy for cancer therapy.

Antimicrobial and hydrophobic cellulose paper prepared by covalently attaching cinnamaldehyde for strawberries preservation.

The demand for paper-based packaging materials as an alternative to incumbent disposable petroleum-derived polymers for food packaging applications is ever-growing. However, typical paper-based formats are not suitable for use in unconventional applications due to inherent limitations (e.g., excessive hydrophilicity, lack antimicrobial ability), and accordingly, enabling new capabilities is necessity. Herein, a simple and environmentally friendly strategy was proposed to introduce antimicrobial and hydrophobic functions to cellulose paper through successive chemical grafting of 3-aminopropyltriethoxysilane (APS) and cinnamaldehyde (CA). The results revealed that cellulose paper not only showed long-term antibacterial effect on different bacteria, but also inhibited a wide range of fungi. Encouragingly, the modified paper, which is fluorine-free, displays a high contact angle of 119.7°. Thus, even in the wet state, the modified paper can still maintain good mechanical strength. Meanwhile, the multifunctional composite papers have excellent biocompatibility and biodegradability. Compared with ordinary cellulose paper, multifunctional composite paper can effectively prolong the shelf life of strawberries. Therefore, the multifunctional composite paper represents good application potential as a fruit packaging material.

Metabolite-derived damage-associated molecular patterns in immunological diseases.

Damage-associated molecular patterns (DAMPs) are typically derived from the endogenous elements of necrosis cells and can trigger inflammatory responses by activating DAMPs-sensing receptors on immune cells. Failure to clear DAMPs may lead to persistent inflammation, thereby contributing to the pathogenesis of immunological diseases. This review focuses on a newly recognized class of DAMPs derived from lipid, glucose, nucleotide, and amino acid metabolic pathways, which are then termed as metabolite-derived DAMPs. This review summarizes the reported molecular mechanisms of these metabolite-derived DAMPs in exacerbating inflammation responses, which may attribute to the pathology of certain types of immunological diseases. Additionally, this review also highlights both direct and indirect clinical interventions that have been explored to mitigate the pathological effects of these DAMPs. By summarizing our current understanding of metabolite-derived DAMPs, this review aims to inspire future thoughts and endeavors on targeted medicinal interventions and the development of therapies for immunological diseases.

Expanding the eukaryotic genetic code with a biosynthesized 21st amino acid.

Genetic code expansion technology allows for the use of noncanonical amino acids (ncAAs) to create semisynthetic organisms for both biochemical and biomedical applications. However, exogenous feeding of chemically synthesized ncAAs at high concentrations is required to compensate for the inefficient cellular uptake and incorporation of these components into proteins, especially in the case of eukaryotic cells and multicellular organisms. To generate organisms capable of autonomously biosynthesizing an ncAA and incorporating it into proteins, we have engineered a metabolic pathway for the synthesis of O-methyltyrosine (OMeY). Specifically, we endowed organisms with a marformycins biosynthetic pathway-derived methyltransferase that efficiently converts tyrosine to OMeY in the presence of the co-factor S-adenosylmethionine. The resulting cells can produce and site-specifically incorporate OMeY into proteins at much higher levels than cells exogenously fed OMeY. To understand the structural basis for the substrate selectivity of the transferase, we solved the X-ray crystal structures of the ligand-free and tyrosine-bound enzymes. Most importantly, we have extended this OMeY biosynthetic system to both mammalian cells and the zebrafish model to enhance the utility of genetic code expansion. The creation of autonomous eukaryotes using a 21st amino acid will make genetic code expansion technology more applicable to multicellular organisms, providing valuable vertebrate models for biological and biomedical research.

Kinetic Analysis of Pulping of Rice Straw with p-Toluene Sulfonic Acid.

The kinetics of pulping of rice straw was studied with p-toluenesulfonic acid (p-TsOH). Pulping with 50% p-TsOH aqueous solution was performed at 70-100 °C for 0-360 min. The results showed that the delignification reaction could be divided into two phases: the bulk delignification phase and the supplementary delignification phase. Lignin dissolution was the main process in the bulk delignification stage, accompanied by the degradation of a small amount of carbohydrates. In the supplementary delignification stage, the delignification rate was low and carbohydrate degradation was severe. The degradation of carbohydrates is mainly based on the dissolution of hemicellulose. A combined delignification factor (CDF) and a combined hydrolysis factor (CHF) were used to compare severity-based kinetic analyses. The results showed that the degradation process for lignin and hemicellulose can be well-fitted using CDF and CHF models. The fitted results show that the activation energy of the hemicellulose loss reaction and delignification reaction was 68.21 and 46.05 kJ/mol, respectively. Therefore, the use of p-TsOH for pulping is a technology with very broad application prospects.

Combination of microsized mineral particles and rosin as a basis for converting cellulosic fibers into "sticky" superhydrophobic paper.

The unique features of cellulosic paper including flexibility, biodegradability, and low cost enables it as a versatile, sustainable biomaterial for promising applications. In the paper industry, microsized mineral particles are widely used in the production of printing/writing paper grades, while rosin derived from trees is the earliest internal sizing agent for paper hydrophobication. On the basis of existing commercial practices associated with the use of mineral particles and rosin in paper production, we present a process concept of converting cellulosic fibers (paper-grade pulp) into "sticky" superhydrophobic paper involving the use of microsized mineral particles and rosin (a tree-derived natural product, mainly a mixture of resin acids, especially abietic acid with chemical formula of C19H29COOH). Internal filling of cellulosic networks with mineral particles was basically used to hold out the mineral particles added at the surface, and the delicate integration of wet-end/surface applications of mineral particles with paper surface engineering with rosin/alum led to the development of "sticky" superhydrophobicity, i.e., ultrahigh water-repellency and strong adhesion to water. This proposed concept may provide valuable implications for expanding the use of paper-based products to unconventional applications, e.g., ultrahigh-performance ink jet printing paper for mitigating the "coffee-ring effect" and paper-based microfluidic devices for biomedical testing.