Single amino acid substitution of VP1 N17D or VP2 H145Y confers acid-resistant phenotype of type Asia1 foot-and-mouth disease virus

Infection by foot-and-mouth disease virus(FMDV) is triggered by the acidic pH in endosomes after virus uptake by receptor-mediated endocytosis. However, dissociation of the FMDV 146S particle in mildly acidic conditions renders inactivated foot-and-mouth disease(FMD) vaccines much less effective. Type Asia1 FMDV mutants with increased resistance to acid inactivation were selected to study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of FMDV. Sequencing of capsid-coding regions revealed four amino acid replacements(VP1 N17D, VP2 H145Y, VP2 G192D, and VP3 K153E) in the viral population of the acid-selected 10th passage. We performed single or combined mutagenesis using a reverse genetic system, and our results provide direct experimental evidence that VP2 H145Y or VP1 N17D substitution confers an acid-resistant phenotype to type Asia1 FMDV.

Efficient adsorption and desorption of Cu^(2+) by a novel acid-resistant magnetic weak acid resin

A novel magnetic weak acid resin NDMC-1 was prepared in the presence of methyl acrylate （MA）, divinylbenzene （DVB） and titanate coupling agent （TCA） coated γ-Fe203 particles. To evaluate the adsorption of Cu^2＋ on the obtained resin NDMC- 1, another two magnetic resins NDMC-0 （the precursor of NDMC-1 without hydrolyzation） and NDMO-1 （the synthesized weak acid resin using oleic acid coated γ-Fe2O3） were chosen for comparison. The results showed that the carboxyl groups were formed after hydrolyzation, and NDMC-1 exhibited a greater adsorption capacity to Cu2~. The desorption experiment demonstrated that the desorption ratio at pH 2 （95.14%） was greatly higher than pH 3 （25.97%）. Moreover, the magnetic resin NDMC-1 was proved to be stable at pH 2, extending the application of magnetic materials which were always considered to be acid-nor, resistant.

Acid-resistant ROS-responsive hyperbranched polythioether micelles for ulcerative colitis therapy

Drug-loaded micelles for oral administration are desired for its conve nience,low cost and flexibility,but current designs rely on introducing pH responsiveness,leaving problems like drug leakage and low accuracy of targeted delivery un-solved.Herein,we reported an acid-resistant ROS-responsive hyperbranched polythioether which can self-assemble into micellar structure and pass through the gastrointestinal tract without leaking drugs.At the inflammatory lesions,the thioester bonds are oxidized to sulphone groups to significantly increase the hydrophilicity in response to accumulated ROS species and efficiently release the encapsulated drugs.Animal experiments,including the evaluation of bodyweight,colon length,MPO activity,spleen index,histology and quantitative reverse transcription PCR,evidenced that the drug-loaded micelles have improved therapeutic efficiency compared to bare drug administration for the treatment of DSS-induced colitis in mice.This study provides an example of oral administrated micellar system can be extended for the treatment of other intestinal tract diseases.

Achieving robust synthetic tolerance in industrial E.coli through negative auto-regulation of a DsrA-Hfq module

In industrial fermentation processes,microorganisms often encounter acid stress,which significantly impact their productivity.This study focused on the acid-resistant module composed of small RNA(sRNA)DsrA and the sRNA chaperone Hfq.Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH,but failed to obtain this desired phenotype in industrial strains.Here,we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode.We then assessed the po-tential of the CymR-based negative auto-regulation(NAR)circuit for industrial application,under different media,strains and pH levels.Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E.coli MG1655.This circuit was robust and worked well in the industrial lysine-producing strain E.coli SCEcL3 at a starting pH of 6.8 and without pH control,resulting in a 250%increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain.This study showed the practical application of NAR circuit in regulating DsrA-Hfq module,effectively and robustly improving the acid tolerance of industrial strains,which provides a new approach for breeding in-dustrial strains with tolerance phenotype.