Aggregation-induced type I&II photosensitivity and photodegradability-based molecular backbones for synergistic antibacterial and cancer phototherapy via photodynamic and photothermal therapies.

The clinical applications of phototherapy nanomaterials are still limited due to concerns regarding their phototoxicity and efficacy. Herein, we report a novel type of D-π-A molecular backbone that induces type I/II photosensitivity and photodegradability by forming J-aggregates. The photodegradation rate can be regulated by changing the donor groups to regulate the photosensitivity of their aggregates because the photodegradability performance results from their oxidation by 1O2 generated by their type II photosensitivity. AID4 NPs possess faster photodegradation because of their better type I&II photosensitivity, which can also self-regulate by inhibiting type II and improving type I under hypoxic conditions. Moreover, they exhibited good photothermal and photoacoustic performance for improving their therapeutic effect by a synergistic effect and achieving photoacoustic imaging in vivo. The experimental result also showed that they can be effective for antibacterial and anti-tumor treatment and the photodegradation products of AID4 NPs possess low biological toxicity in the dark or under light. This study could provide a novel strategy for improving the safety and treatment effects of phototherapy.

Promotion of astrocyte-neuron glutamate-glutamine shuttle by SCFA contributes to the alleviation of Alzheimer's disease.

The brain is particularly susceptible to oxidative damage which is a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The shuttling of glutathione (GSH) precursors from astrocytes to neurons has been shown to be instrumental for the neuroprotective activity. Here, we revealed that short chain fatty acids (SCFA), which have been related to AD and PD, could promote glutamate-glutamine shuttle to potentially resist oxidative damage in neurons at cellular level. Furthermore, we performed nine-month-long dietary SCFA supplementations in APPswe/PS1dE9 (APP/PS1) mice, and showed that it reshaped the homeostasis of microbiota and alleviated the cognitive impairment by reducing Aß deposition and tau hyperphosphorylation. Single-cell RNA sequencing analysis of the hippocampus revealed SCFA can enhance astrocyte-neuron communication including glutamate-glutamine shuttle, mainly by acting on astrocyte in vivo. Collectively, our findings indicate that long-term dietary SCFA supplementations at early aging stage can regulate the neuroenergetics to alleviate AD, providing a promising direction for the development of new AD drug.

Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.

Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation.

The excessive M1 polarization of macrophages drives the occurrence and development of inflammatory diseases. The reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Taurine promotes for the balance of energy metabolism and the repair of inflammatory injury, preventing chronic diseases and complications. However, little is known about the mechanisms underlying the action of taurine modulating the macrophage polarization phenotype. In this study, we constructed a low-dose LPS/IFN-γ-induced M1 polarization model to simulate a low-grade pro-inflammatory process. Our results indicate that the taurine transporter TauT/SlC6A6 is upregulated at the transcriptional level during M1 macrophage polarization. The nutrient uptake signal on the membrane supports the high abundance of taurine in macrophages after taurine supplementation, which weakens the status of methionine metabolism, resulting in insufficient S-adenosylmethionine (SAM). The low availability of SAM is directly sensed by LCMT-1 and PME-1, hindering PP2Ac methylation. PP2Ac methylation was found to be necessary for M1 polarization, including the positive regulation of VDAC1 and PINK1. Furthermore, its activation was found to promote the elimination of mitochondria by macrophages via the mitophagy pathway for metabolic adaptation. Mechanistically, taurine inhibits SAM-dependent PP2Ac methylation to block PINK1-mediated mitophagy flux, thereby maintaining a high mitochondrial density, which ultimately hinders the conversion of energy metabolism to glycolysis required for M1. Our findings reveal a novel mechanism of taurine-coupled M1 macrophage energy metabolism, providing novel insights into the occurrence and prevention of low-grade inflammation, and propose that the sensing of taurine and SAM availability may allow communication to inflammatory response in macrophages.

Evaluation of Ficus tikoua leaves extract as an eco-friendly corrosion inhibitor for carbon steel in HCl media.

An effective and biodegradable Ficus tikoua leaves extract was studied as a corrosion inhibitor for carbon steel in hydrochloric acid. Systematic electrochemical experiments and morphological characterization were carried out to investigate the properties of the corrosion inhibitor. Meanwhile, quantum chemical calculations were performed to aid further understanding of the electrochemical mechanism. The electrochemical results reveal that the extract inhibitors act as a mixed-type with an inhibition efficiency up to 95.8% at 298 K. Moreover, this extract shows good inhibory activity at a wide range of temperatures and the corresponding results were further confirmed by morphological analysis. The chemical formulae of these major components are fully optimized in the DFT with B3LYP in the gas phase and the base set is 6-311++G (d, p).