Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

Deciphering Erasing/Writing/Reading of Near-Infrared Fluorophore for Nonvolatile Optical Memory.

A near-infrared fluorescence-switchable molecule, dithienylethene-terrylenediimide (TDI-4DTE) exhibits high near-infrared fluorescence and on/off ratio, decent reversibility, and fatigue resistance upon alternating UV/vis (305/621 nm) irradiation. Photoinduced electron transfer mainly contributes to the fluorescence quenching of TDI-4DTE. As an information storage unit, single molecular TDI-4DTE in the polymer film can be written by red light (621 nm) and erased by UV light (305 nm), while nondestructive fluorescence readout (750 nm) of a single molecular memory has been obtained upon excitation with near-infrared light (720 nm). The fluorescence patterning of TDI-4DTE in the polymer film demonstrates that the erasing/writing/reading wavelengths are deciphered to minimize the signal crosstalk in nonvolatile fluorescent molecular memories.

Photoplastic Transformation Based on Dynamic Covalent Chemistry.

The magical fantasy of decades-old transformer characters is becoming closer to scientific reality, as transformable materials can change their shapes in response to thermal, mechanical, electrical, and chemical stimuli. However, precise and prompt control of plastic shaping remains to be wanted. Photoresponsive materials provide a promising alternative for rapid optomechanical shaping with limited success. Here, we report a new class of photoplastic transformation based on dynamic covalently crosslinked polytriazole (PTA) networks, in which crosslinking points are comprised of photocleaveable hexaarylbiimidazole (HABI). Upon sub-500 nm light irradiation, HABI is dissociated into two triphenylimidazole radicals (TPIRs) followed by spontaneous recombination back to the initial state. This photoswitching effect is demonstrated to generate nonthermal shape change in the PTA-HABI gel network at will upon light stimulus. A unique photoalignment phenomenon has also been discovered which can form oriented nanoscale patterning in the PTA-HABI gel network upon laser irradiation. The solvent-free PTA-HABI elastomer exhibits photoenhanced automatic self-healing properties at temperatures ranging from 25 °C to freezing points, which is attributed to the dynamic equilibrium between TPIRs and HABI. A photoplastic spring is fabricated and exhibits photoswitchable plastic behavior, i.e., a reversible transformation between plastic strain and elastic strain upon light irradiation. HABI-based polymer networks, including solvated gel and solvent-free elastomer, are promising as smart materials for nonthermal photoactivated shape changing, transformation, and self-healing applications.

Photoswitchable Self-Assembly/Disassembly of Near-Infrared Fluorophores.

A new photoswitchable near-infrared fluorophore (TDI-4DTE) with a symmetric structure exhibited reversible photo-controllable self-assembly and disassembly. The modification of π-conjugated terrylenediimide with four dithienylethene groups not only induced photoswitchable near-infrared fluorescence, but also photoregulated reversible precipitation-dissolution with microscopic and macroscopic polymorphism. Upon 302 nm UV-light irradiation, a noticeable precipitation was observed within seconds. The precipitate was gradually dissolved again in half an hour upon visible light irradiation. Different microscopic morphologies of the precipitates, including nanoparticles, nanofibrils and nanosheets, were observed when altering the intensity of the 302 nm light irradiation, indicating the dynamic control process of self-assembly. Upon UV-light irradiation, TDI-4DTE nanosheets were also obtained as a solid polymeric film, whereas well-defined nanoribbons with molecular monolayer thickness formed at the oil/water interface with slower assembly dynamics.

PEGylated Perylenemonoimide-Dithienylethene for Super-Resolution Imaging of Liposomes.

We have designed and synthesized an amphiphilic photoswitchable fluorophore, PEGylated perylenemonoimide-dithienylethene (PEG-PMI-DTE), which exhibits evident bistable photochromism, fluorescence switching, and fatigue resistance. The fine nanostructures of liposomes can be observed directly under super-resolution fluorescent microscopy by aid of the amphiphilic photoswitchable fluorophore as a staining agent, with an optical resolution of 30 nm.

Monodisperse AIE-Active Conjugated Polymer Nanoparticles via Dispersion Polymerization Using Geminal Cross-Coupling of 1,1-Dibromoolefins.

Monodisperse AIE (aggregation-induced emission)-active conjugated polymer nanoparticles are synthesized by dispersion polymerization using geminal Suzuki cross-coupling of 1,1-dibromoolefins. The size of the nanoparticles can be adjusted by varying the concentration of the initial monomer.

The synthesis and aggregation-induced near-infrared emission of terrylenediimide-tetraphenylethene dyads.

We design and synthesize terrylenediimide-tetraphenylethene dyads, which exhibit featured aggregation-induced near-infrared fluorescence with a maximum emission wavelength of up to 800 nm.