Search

5-Hydroxymethylfurfural (5-HMF) exists in a wide range of sugar-rich foods and traditional Chinese medicines. The role of 5-HMF in antiviral innate immunity and its mechanism have not been reported previously. In this study, we reveal for the first time that 5-HMF upregulates the production of retinoic acid-inducible gene I (RIG-I)-mediated type I interferon (IFN) as a response to viral infection. IFN-β and IFN-stimulated chemokine gene expressions induced by the vesicular stomatitis virus (VSV) are upregulated in RAW264.7 cells and primary peritoneal macrophages after treatment with 5-HMF, a natural product that appears to inhibit the efficiency of viral replication. Meanwhile, 5-HMF-pretreated mice show enhanced innate antiviral immunity, increased serum levels of IFN-β, and reduced morbidity and viral loads upon infection with VSV. Thus, 5-HMF can be seen to have a positive effect on enhancing type I IFN production. Mechanistically, 5-HMF upregulates the expression of RIG-I in macrophages, resulting in an acceleration of the RIG-I signaling pathway activation. Additionally, STAT1 and STAT2 phosphorylations, along with the expression of IFN-stimulated chemokine genes induced by IFN-α/β, were also enhanced in macrophages cotreated with 5-HMF. In summary, these findings indicate that 5-HMF not only can induce type I IFN production but also can enhance IFN-JAK/STAT signaling, leading to a novel immunomodulatory mechanism against viral infection. In conclusion, our study reveals a previously unrecognized effect of 5-HMF in the antiviral innate immune response and suggests new potential of utilizing 5-HMF for controlling viral infection.

Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA., Non-obstructive azoospermia affects 1% of men. Here, authors perform single-cell transcriptomic analysis of human testicular cells from healthy donors and non-obstructive azoospermia patients and find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from patients.

A flexible porous water-soluble supramolecular organic framework was developed, which could efficiently exhibit phosphorescence both in an aqueous phase and in a film state at room-temperature.

Pure organic room-temperature phosphorescence (RTP) materials have attracted wide attention for their easy preparation, low toxicity and applications in professional fields such as bioimaging and anti-counterfeiting. Developing phosphorescent systems with more universality and less difficulty in synthesis has long been the pursuit of materials scientists. By employing polymeric quaternary ammonium salt with an ionic bonding matrix and heavy atoms, commercial fluorescent dyes are directly endowed with phosphorescence emission. In a single amorphous polymer, the external heavy-atom effect generates excited triplet states, which are further stabilized by the rigid polymer matrix. This study proposed a new general strategy to design and develop pure organic RTP materials starting from the vast library of organic dyes without complicated chemical synthesis.

Pure organic room-temperature phosphorescence (RTP) materials are useful for photoelectric, biochemical devices, and bioimaging sensors. In the last few years, dynamic covalent chemistry has aroused substantial attention as it offers a way to create intelligent materials with feedback and response functions. Through a Diels-Alder reaction, a [4+2] cycloaddition reaction between dienes and dienophiles, three polymers were synthesized that can be reversibly transformed by thermally reversible dynamic covalent bonds. All polymers show decent RTP emission with different colors. For the poly-Br-An solid, the absolute phosphorescence quantum yield reaches up to 12 %. This study provides a new method for the rational design and synthesis of tunable-emission organic RTP materials via dynamic covalent bonds.

In the present study, we developed a multicompartmental toxicokinetic model for two polycyclic aromatic hydrocarbons (phenanthrene and anthracene) in their deuterated form (PAHs-d10) in zebrafish considering continuous waterborne uptake and discrete dietary uptake. We quantified the bioconcentration, bioaccumulation, and depuration of these two PAHs-d10 in zebrafish, and then estimated the kinetic parameters by fitting the model into the experimental data. The experimental and fitting results both showed that there was a peak concentration in each compartment of zebrafish after every dietary uptake, while the peak value depended on the ingestion amount of the PAH-d10 and varied among different compartments. The PAH-d10 amount in the blood reached 20-27% of the total amount bioaccumulated in zebrafish at steady-state, followed by skin (20-26%), and fillet (16-22%). The rank of PAH-d10 steady-state concentrations in each compartment showed inconsistency with its lipid contents, indicating that the distribution of the PAHs-d10 in zebrafish was not merely affected by the lipid content in each compartment, but also affected by their kinetics and biotransformation. This study suggests that discrete dietary uptake caused by intermittent food ingestion significantly affects the bioaccumulation of PAHs in fish. Further studies are needed to investigate such effect on other toxicants that are more resistant to biotransformation than PAHs in fish.