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The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.

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Major histocompatibility Complex class I (MHC I) molecules are ubiquitously expressed, being found in most nucleated cells, where they are central mediators of both the adaptive and innate immune responses. Recent studies have shown that MHC I are also expressed in the developing brain where they participate in synapse elimination and plasticity. Up‐regulation of MHC I within the developing brain has been reported, however, the mechanism(s) regulating this developmental up‐regulation of neuronal MHC I remains unknown. Here, we show NLR family CARD domain containing 5 (NLRC5), a newly identified member of the NLR family, is widely expressed in hippocampal neurons, and the expression pattern of NLRC5 coincides with increased MHC I mRNA in the developing hippocampus. Using a luciferase assay in Neuro‐2a cells we demonstrate that NLRC5 can induce the activation of MHC I and this induction requires the W/S‐X‐Y motif. Further studies show that transcription factors regulatory factor X (RFX) and CREB1, which bind to X1 and X2 box, are crucial for NLRC5‐mediated induction. Moreover immunoprecipitation experiments reveal that NLRC5 interacts with RFX subunits RFX5 and RFXANK. Knockout of Nlrc5 dramatically impairs basal expression of MHC I in mouse hippocampus. Taken together, our findings identify NLRC5 as a key regulator of MHC I up‐regulation in the developing hippocampus and suggest an important role for NLRC5 in neurons. Cover Image for this issue: doi: .

MiRNAs are small regulatory RNAs that play crucial roles in the oncogenic state in various cancers and have shown highly promising clinical applications as plasma-based markers for cancer classification and prognostication. Due to their electroanalytical advantages, photoelectrochemical biosensors are a very attractive alternative technology for miRNA sensing and detection. In this work, we demonstrated a novel photoelectrochemical (PEC) sensor using the in situ grown Au nanoparticles/two-dimensional molybdenum disulfide (MoS2) nanosheet heterojunction (MoS2-AuNPs) on ITO glass as the photoanode (MoS2-AuNPs/ITO). AuNPs were used as a photoelectronic transfer promoter and DNA probe immobilization carrier as well. The thiol modified biotin DNA with a hairpin structure was tethered to the MoS2-AuNPs/ITO surface to form a specific capturing layer for miRNA detection. The biotin specific protein streptavidin was used as the signal amplifying species. This PEC sensor is structurally simple and possesses sensitivity and specificity toward miRNA. The CV and EIS responses were evaluated to monitor the PEC anode fabrication. The stability and reproducibility of this PEC design strategy were both evaluated before it was used in analyzing the samples of miRNA in human serum. Finally, we found that this PEC sensor displayed a broad detection linear range and a low detection limit of 4.21 fM, and it can excellently discriminate the mismatched miRNA. These findings pave the way for developing PEC sensors targeting miRNA by using noble metals/MoS2 heterojunctions.

The School of Pharmaceutical Science, Shandong University, Ji'nan, Shandong Province, PR China Abstract Tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL), loaded nanostructured lipid carrier (Am80-NLC) was developed and characterized previously. The purpose of the present work was to develop PEGylated nanostructured lipid carrier (PEG-NLC) for intravenous delivery of Am80, with the aim to further extend the circulation in blood and decrease the adverse events. Am80-loaded PEG-NLC (Am80-PEG-NLC) modified with PEG-40 stearate (PEG40-SA, molecular weight 2000 Da) was formulated by the method of melt-emulsification and low temperature-solidification technique. Am80-NLC was developed as well as control. Based on the optimized results of single-factor screening experiment, the average drug entrapment efficiency, the mean particle size, and zeta potential of Am80-NLC and Am80-PEG-NLC were found to be 89.8-94.3%, 178.9-201.6 nm, and À37.74 to À20.1 mV, respectively. In vitro drug release of Am80-NLC and Am80-PEG-NLC possessed a sustained release characteristic and their release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous (i.v.) injection to rats, the mean residence time (MRT) of Am80-PEG-NLC group was significantly prolonged and the AUC value was improved as well compared with the Am80-NLC group. Furthermore, the biodistribution in mice showed that Am80-PEG-NLC preferentially decreased the accumulation of Am80 in kidney and increased the drug concentration in brain after i.v. injection. In conclusion, Am80-PEG-NLC may be a potential delivery system for Am80 in the treatment of APL.

Polydispersity of TX-100 surfactant affects the structure of reverse micelles remarkably, and TX-100 with 5–10 EO units endows the micelles with hierarchical micellar interface, favoring for the preparation of monodisperse silica nanoparticles.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for breast cancer, but PTX resistance often occurs in metastatic breast cancer. In addition, due to the poor targeting of chemotherapeutic drugs and the presence of the blood−brain barrier (BBB), it is hard to effectively treat brain metastatic breast cancer using paclitaxel. Thus, it is urgent to develop an effective drug delivery system for the treatment of brain metastatic breast cancer. The current study found that TWF1 gene, an epithelial−mesenchymal transition-associated gene, was overexpressed in brain metastatic breast cancer (231-BR) cells and was associated with the PTX resistance of 231-BR cells. Knockdown of TWF1 by small interference RNA (siRNA) in 231-BR cells could effectively increase the sensitivity of brain metastatic breast cancer cells to paclitaxel. Then, a liposome-based drug delivery system was developed for PTX delivery across BBB, enhancing PTX sensitivity and brain metastases targeting via BRBP1 peptide modification. The results showed that BRBP1-modified liposomes could effectively cross the BBB, specifically accumulate in brain metastases, and effectively interfere TWF1 gene expression in vitro and in vivo, and thus they enhanced proliferation inhibition, cell cycle arrest, and apoptosis induction, thereby inhibiting the formation and growth of brain metastases. In summary, our results indicated that BRBP1-modified and PTX-and TWF1 siRNA-loaded liposomes have the potential for the treatment of brain metastatic breast cancer, which lays the foundation for the development of a new targeted drug delivery system.