Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

Insight into a natural novel histidine decarboxylase gene deletion in Enterobacter hormaechei RH3 from traditional Sichuan-style sausage.

Histamine (HIS) is primarily formed from decarboxylated histidine by certain bacteria with histidine decarboxylase (hdc) activity and is the most toxic biogenic amine. Hdc, which is encoded by the hdc gene, serves as a key enzyme that controls HIS production in bacteria. In this paper, we characterized the changes in microbial and biogenic amines content of traditional Sichuan-style sausage before and after storage and demonstrated that Enterobacteriaceae play an important role in the formation of HIS. To screen for Enterobacteriaceae with high levels of HIS production, we isolated strain RH3 which has a HIS production of 2.27 mg/mL from sausages stored at 37°C for 180 days, using selective media and high-performance liquid chromatography. The strain RH3 can produce a high level of HIS after 28 h of fermentation with a significant hysteresis. Analysis of the physicochemical factors revealed that RH3 still retained its ability to partially produce HIS in extreme environments with pH 3.5 and 10.0. In addition, RH3 exhibited excellent salt tolerance (6.0% NaCl and 1.0% NaNO2 ). Subsequently, RH3 was confirmed as Enterobacter hormaechei with hdc gene deletion by PCR, western blot, and whole-genome sequencing analysis. Furthermore, RH3 exhibited pathogenicity rate of 75.60% toward the organism, indicating that it was not a food-grade safe strain, and demonstrated a high level of conservation in intraspecific evolution. The results of this experiment provide a new reference for studying the mechanism of HIS formation in microorganisms. PRACTICAL APPLICATION: This study provides a new direction for investigating the mechanism of histamine (HIS) formation by microorganisms and provides new insights for further controlling HIS levels in meat products. Further research can control the key enzymes that form HIS to control HIS levels in food.

Research of Multicopper Oxidase and Its Degradation of Histamine in Lactiplantibacillus plantarum LPZN19.

In order to explore the structural changes and products of histamine degradation by multicopper oxidase (MCO) in Lactiplantibacillus plantarum LPZN19, a 1500 bp MCO gene in L. plantarum LPZN19 was cloned, and the recombinant MCO was expressed in E. coli BL21 (DE3). After purification by Ni2+-NTA affinity chromatography, the obtained MCO has a molecular weight of 58 kDa, and it also has the highest enzyme activity at 50 °C and pH 3.5, with a relative enzyme activity of 100%, and it maintains 57.71% of the relative enzyme activity at 5% salt concentration. The secondary structure of MCO was determined by circular dichroism, in which the proportions of the α-helix, ß-sheet, ß-turn and random coil were 2.9%, 39.7%, 21.2% and 36.1%, respectively. The 6xj0.1.A with a credibility of 68.21% was selected as the template to predict the tertiary structure of MCO in L. plantarum LPZN19, and the results indicated that the main components of the tertiary structure of MCO were formed by the further coiling and folding of a random coil and ß-sheet. Histamine could change the spatial structure of MCO by increasing the content of the α-helix and ß-sheet. Finally, the LC-MS/MS identification results suggest that the histamine was degraded into imidazole acetaldehyde, hydrogen peroxide and ammonia.

Anion receptor and heavy metal-free redox mediator decorated separator for lithium-sulfur batteries.

The adsorption-catalysis synergy for accelerated conversion of polysulfides is critical toward the electrochemical stability of lithium-sulfur battery (LSB). Herein, a non-metallic polymer network with anion receptor units, trifluoromethanesulfonyl (CF3SO2-) substituted aza-ether, was in-situ integrated on PE separator, working as an efficient host for anchoring lithium thiophosphates (LPS) as redox mediators and polysulfides through Lewis acid-base interaction. The anchored LPS on the modified PE separator displayed a robust chemical adsorption ability towards polysulfides through the formation of SS bond. Meanwhile, LPS decreased the energy barrier of Li2S nucleation and promoted redox reaction kinetics. The battery with LPS decorated separator revealed a long cycling lifespan with a per cycle decay of 0.056 % after 600 cycles, and a competitive initial capacity of 889.1 mAh/g when the of sulfur cathode increased to 3 mg cm-2. This work developed a new design strategy to promote the utilization of lithium phosphorus sulfide compounds in LSB.

Bioinspired Separator with Ion-Selective Nanochannels for Lithium Metal Batteries.

The free transport of anions through commercial polyolefin separators used in lithium metal batteries (LMBs) gives rise to concentration polarization and rapid growth of lithium dendrites, leading to poor performance and short circuits. Here, a new poly(ethylene-co-acrylic acid) (EAA) separator with functional active sites (i.e., carboxyl groups) distributing along the pore surface was fabricated, forming bioinspired ion-conducting nanochannels within the separator. As the carboxyl groups effectively desolvated Li+ and immobilized anion, the as-prepared EAA separator selectively accelerated the transport of Li+ with transference number of Li+ (tLi+) up to 0.67, which was further confirmed by molecular dynamics simulations. The battery with the EAA separator can be stably cycled over 500 h at 5 mA cm-2. The LMBs with the EAA separator have exceptional electrochemical performance of 107 mAh g-1 at 5 C and a capacity retention of 69% after 200 cycles. This work provides new commercializable separators toward dendrite-free LMBs.