Constructing ROS-Responsive Supramolecular Gel with Innate Antibacterial Properties.

Bacterial infections, especially antibiotic-resistant bacterial infections, pose a significant threat to human health. Supramolecular gel with innate antibacterial properties is an advanced material for the treatment of bacterial infections, which have attracted great attention. Herein, a reactive oxygen species (ROS)-responsive innate antibacterial supramolecular gel is developed by a bottom-up approach based on phenylalanine and hydrazide with innate antibacterial properties. The structure of gelators and intermediate products was characterized by proton nuclear magnetic resonance (1H NMR) and a high-resolution mass spectrum (HRMS). The results of 1H NMR and the Fourier transform infrared spectrum (FT-IR) experiment disclosed that hydrogen bonding and the π-π stacking force are the important self-assembly driving forces of gelators. The microstructure and mechanical properties of gel were studied by Scanning electron microscope (SEM) and Rheometer, respectively. An in vitro degradation experiment proved that the gelator has ROS-responsive degradation properties. The in vitro drug release experiment further manifested that antibiotic-loaded gel has ROS-responsive drug-release performances. An in vitro cytotoxicity experiment showed that the supramolecular gel has good biocompatibility and could promote cell proliferation. The in vitro antibacterial experiment proved that the supramolecular gel has excellent inherent antibacterial properties, and the antibacterial rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was 98.6% and 99.1%, respectively. The ROS-responsive supramolecular gel as a novel antibacterial agent has great application prospects in treating antibiotic-resistant bacterial-infected wounds and preventing the development of bacterial resistance.

Mitochondria-Targeting Polymer Micelles in Stepwise Response Releasing Gemcitabine and Destroying the Mitochondria and Nucleus for Combined Antitumor Chemotherapy.

Mitochondrial DNA and nuclear DNA are essential genetic material which play an important role in maintaining normal metabolism, survival, and proliferation of cells. Constructing a mitochondria-targeting stimuli-responsive nano-drug delivery system releasing chemotherapeutic agents in a stepwise response manner and destroying mitochondrial DNA and nuclear DNA simultaneously is an effective way to improve the anti-tumor effect of chemotherapeutic agents. In this study, a new mitochondria-targeting pH/ROS dual-responsive block copolymer TPP-PEG2k-b-(BS-AA)n (P1), untargeted pH/ROS dual-responsive copolymer mPEG2k-b-(BS-AA)n (P2), pH single-responsive copolymer (mPEG2k-b-(AH-AA)n (P3), ROS single-responsive copolymer mPEG2k-b-(SA-TG)n (P4), and non-responsive copolymer mPEG-b-PCL (P5) were constructed. pH/ROS-responsive properties were characterized by proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS). Anticancer chemotherapeutic agent gemcitabine (GEM) or fluorescent substance Nile Red (NR) were loaded in the polymer micelles. Results of the mitochondrial colocalization experiment indicate that (5-carboxypentyl)(triphenyl)phosphonium bromide (TPP)-functionalized P1 micelles could be efficiently targeted and located in mitochondria. Results of the cellular uptake experiment showed that pH/ROS dual-responsive GEM-loaded P1 and P2 micelles have faster internalized and entry nucleus rates than single-responsive or non-responsive GEM-loaded micelles. The in vitro release experiment suggests pH/ROS dual-responsive GEM/P1 and GEM/P2 micelles have higher cumulative release than single-responsive GEM/P3 and GEM/P4 micelles. The in vitro cytotoxic experiment shows that the mitochondria-targeted dual-responsive GEM/P1 micelles had the lowest IC50 values, and the cytotoxic effect of dual-responsive GEM/P2 micelles was superior to the single-responsive and non-responsive drug-loaded micelles.

Establishment of a quantitative RT-PCR detection of SARS-CoV-2 virus.

BACKGROUND: The outbreak of novel coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. Quantitative testing of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus is demanded in evaluating the efficacy of antiviral drugs and vaccines and RT-PCR can be widely deployed in the clinical assay of viral loads. Here, we developed a quantitative RT-PCR method for SARS-CoV-2 virus detection in this study. METHODS: RT-PCR kits targeting E (envelope) gene, N (nucleocapsid) gene and RdRP (RNA-dependent RNA polymerase) gene of SARS-CoV-2 from Roche Diagnostics were evaluated and E gene kit was employed for quantitative detection of COVID-19 virus using Cobas Z480. Viral load was calculated according to the standard curve established by series dilution of an E-gene RNA standard provided by Tib-Molbiol (a division of Roche Diagnostics). Assay performance was evaluated. RESULTS: The performance of the assay is acceptable with limit of detection (LOD) below 10E1 copies/µL and lower limit of quantification (LLOQ) as 10E2 copies/µL. CONCLUSION: A quantitative detection of the COVID-19 virus based on RT-PCR was established.

Comparison of the Effects of Green and Black Tea Extracts on Na+ /K+ -ATPase Activity in Intestine of Type 1 and Type 2 Diabetic Mice.

SCOPE: Na+ /K+ -ATPase is an important membrane-bound enzyme and high levels of Na+ /K+ -ATPase activity in intestine result in increased monosaccharide absorption and aggravated undesirable postprandial hyperglycemia in diabetic. The aim is to characterize the effects of green and black tea extracts on the intestinal Na+ /K+ -ATPase. METHODS AND RESULTS: The STZ-induced type 1 diabetic mice model and high-fat diet combined with low-dose STZ-induced type 2 diabetic mice model are used in this study and the data indicate that both green and black tea extracts show significant hypoglycemic effect. The Na+ /K+ -ATPase activities in intestine associated with glucose absorption are increased in type 1 diabetic mice, while those are even normal in type 2 diabetic mice. Green and black tea extracts can attenuate type 1 diabetes-induced intestinal Na+ /K+ -ATPase disturbance to control postprandial hyperglycemia. Black tea is more effective than green tea in reducing of Na+ /K+ -ATPase activity and protein expression. Theaflavins are the major functional components of black tea and theaflavine-3,3'-digallate presents the strongest inhibitory effect exhibiting anticompetition with ATP and mixed inhibition with Na+ and K+ . CONCLUSION: Tea, especially black tea, can be considered a potential therapeutic agent against type 1 diabetes-induced intestinal Na+ /K+ -ATPase disturbance to control postprandial hyperglycemia.

Evidence for implicit self-positivity bias: an event-related brain potential study.

We investigated the processing of self-related information under the prime paradigm using event-related potentials (ERPs) to provide evidence for implicit self-positivity bias in Chinese individuals. Reaction times and ERPs were recorded when participants made positive/negative emotional judgments to personality-trait adjectives about themselves or others. Faster responses occurred to self-related positive adjectives and other-related negative adjectives, indicating implicit self-positivity bias at the behavioral level. ERPs showed an interaction between prime and emotion at the P300 amplitude, with larger P300 amplitudes for words within the self-positivity bias, indicating that self-related information occupied more attentional resources. Larger N400 amplitudes elicited by words that were inconsistent with the self-positivity bias, suggesting that accessing non-self-relevant information is more difficult than self-relevant information. Thus, P300 and N400 could be used as neuro-indexes of the implicit self-positivity bias.

Electrophysiological correlation of the degree of self-reference effect.

The present study investigated neural correlations underlying the psychological processing of stimuli with various degrees of self-relevance. Event-related potentials were recorded for names that differ in their extent of relevance to the study participant. Participants performed a three-stimulus oddball task. ERP results showed larger P2 averaged amplitudes for highly self-relevant names than for moderately self-relevant, minimally self-relevant, and non-self-relevant names. N2 averaged amplitudes were larger for the highly self-relevant names than for the moderately self-relevant, minimally self-relevant, and non-self-relevant names. Highly self-relevant names elicited larger P3 averaged amplitudes than the moderately self-relevant names which, in turn, had larger P3 values than for minimally self-relevant names. Minimally self-relevant stimuli elicited larger P3 averaged amplitudes than non-self-relevant stimuli. These results demonstrate a degree effect of self-reference, which was indexed using electrophysiological activity.