Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

Modeling of heat transfer and thermal regulation for an electric heating glove against a cold environment.

An electric heating glove can protect the health of workers without affecting flexibility of the hand in a cold environment. A heat transfer model of an electric heating glove with a function of intelligent temperature control was established. The model was verified by a test device for simulating cold-contact exposure. The results showed good agreement between the simulated values and the experimental values. Based on the numerical model, the basic parameters of the electric heating glove were analyzed. It was found that the pressure, thickness and thermal conductivity of the outer fabric were the key factors affecting the thermal regulative performance of the electric heating glove. The power consumption of the electric heating glove was mainly determined by the thickness of the outer fabric. The developed model provides a theoretical basis for the design of an electric heating glove for a thermal regulative effect and energy saving.

Total synthesis and stereochemical assignment of rakicidin F.

Total synthesis of rakicidin F was accomplished in 20 linear steps (0.68% overall yield), which enabled the configural determination of its six stereogenic centers as 2R, 15R, 16R, 17S, 19S, and 21S. The macrolactonization of the rakicidin linear precursor was investigated and the unsuccessful results might be attributed to the steric hindrance near C16-OH.

Levistilide A Promotes Expansion of Human Umbilical Cord Blood Hematopoietic Stem Cells by Enhancing Antioxidant Activity.

Several approaches to expand human hematopoietic stem cells (hHSCs) clinically along with retainable capability of multipotential differentiation have been reported, but only a few have advanced to evaluation in clinical trials, which limits the application of HSC-based therapy. Here we show a phthalide derivative, Levistilide A (LA), can serve as a promising molecule to expand functional human umbilical cord blood (UCB) HSCs ex vivo. An in-house screen identified LA out of nine natural products as an outstanding candidate for hHSCs expansion. Additionally, our data indicated that LA treatment not only increased the numbers of phenotype-defined HSCs, but also enhanced their colony formation ability. Xenotransplantation assays showed that LA treatment could maintain unaffected engraftment of hHSCs with multilineage differentiation capacity. Further experiments revealed that LA enhanced the antioxidant activity of hHSCs by reducing intracellular and mitochondrial reactive oxygen species (ROS) levels. The identification of LA provides a new strategy in solving the clinical issue of limited numbers of UCB HSCs.

Total Synthesis and Determination of the Absolute Configuration of Rakicidin C.

The absolute configuration of rakicidin C was predicted by comparison of optical rotation data and absolute configuration of APD-cyclic depsipeptides and further determined by total synthesis. The absolute configuration of five chiral centers was determined as 2R, 15R, 16R, 17S, and 19S. Our efficient route involves 19 longest linear steps with an overall yield of 1.49%.

Total Synthesis and Structure Revision of Boholamide A.

The 15-membered cyclic depsipeptide boholamide A and an epimer were prepared by total synthesis for the first time, thus leading to a revision of C6 stereochemistry in the originally proposed structure of natural boholamide A. This convergent route features achievement of a macro-lactamization step in a gram scale. The revised boholamide A was sythesized with 16 linear steps in 5.46% overall yield. This work facilitates the investigations of boholamide A as a potential hypoxia-selective anticancer agent.

A porous Au-Ag hybrid nanoparticle array with broadband absorption and high-density hotspots for stable SERS analysis.

Constructing high-density hotspots is of crucial importance in surface enhanced Raman scattering (SERS). In this paper, we present a large-area and broadband porous Au-Ag hybrid nanoparticle array which was fabricated by an ultra-thin alumina mask (UTAM) technique incorporated with annealing and galvanic replacement techniques. Experimental results and numerical simulations demonstrated that the porous Au-Ag hybrid nanoparticle array possessed enormous hotspots for high sensitivity, uniformity, and stability in SERS analysis. A large Raman enhancement factor of 2.2 × 107 was achieved with a relative standard deviation (RSD) of 7.7%, leading to excellent reliability for Raman detection. Furthermore, this novel substrate exhibited a long shelf time in an ambient environment and promising practical applications in many SERS-based quantitative analytical and biomedical sensing techniques.