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Delayed neurocognitive recovery (dNCR) is a prevalent perioperative neurological complication in older patients and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enclosed by a lipid bilayer contain proteins, DNA, miRNA, and other components, which are important mediators of intercellular communication. It has been reported that exosomes could play an important role in the treatment of neurodegenerative diseases, nerve injury, and other neurological diseases. In this study, we examined the effects of MSCs-Exo on dNCR aged mice after exploratory laparotomy and evaluated their potential regulatory mechanisms. We found that MSCs-Exo treatment ameliorated cognitive impairment in dNCR aged mice. MSCs-Exo inhibit hippocampus ferroptosis and increase the expression of silent information regulator 1 (SIRT1), factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in dNCR aged mice. Interestingly, the above effects of MSCs-Exo on dNCR aged mice were abolished by SIRT1 selective inhibitor EX-527. In conclusion, these findings indicated that MSCs-Exo can ameliorate cognitive impairment by inhibiting hippocampus ferroptosis in dNCR aged mice via activating SIRT1/Nrf2/HO-1 signaling pathway, providing a potential avenue for the treatment of dNCR.

Agarose is a promising tool for encapsulating areas as a kind of neutral polysaccharide. The purpose of this work is to expand the application of agarose. In this work, agarose microparticles for encapsulating microorganisms were introduced to the stomach through a novel water-in-water (w/w) emulsification method. Sequencing techniques were performed for the identification and characterization of bacteria, and drug-susceptibility testing of Helicobacter pylori through gel microdroplets growth assay and traditional Oxford cup method was conducted. Results indicated the presence of three phyla, eight genera, and more than 30 species in the samples. The correlation values of the traditional Oxford cup and GMD methods were 87.5% and 90%, respectively. The proposed encapsulation technology as efficient substitution for traditional Oxford cup method promised to be applicable for the isolation and cultivation of gastric flora. Compared to other methods, this new method showed advantages when mainly due to time simplicity of the whole process. The direct drug susceptibility test based on the novel encapsulation technology is a promising tool for the rational and flexible use of drugs in clinical practice. Furthermore, this work was an early exploration for the combination of encapsulation technology and agarose.

Aims: Atrial fibrosis is the hallmark of atrial fibrillation (AF). Accumulating evidence have shown that mesenchymal stem cells (MSCs) can alleviate fibrosis in diverse organs. However, the role of MSCs-derived exosome (MSCs-Exo) in the pathogenesis of atrial fibrosis and vulnerability to AF was unknown.Methods: Exosomes were isolated from cultured MSCs. Transmission electron microscopy and western blot were used to examine the purity of MSCs-Exo. 8-week-old BALB/c mice were randomized into sham group, angiotensin-II (Ang-II) group, and Ang-II+MSCs-Exo group. A mini-pump was implanted for subcutaneous infusion of Ang-II for 4 weeks to induce atrial fibrosis. In the Ang-II+MSCs-Exo group, 300μg/150μl MSCs-Exo were injected into tail veins twice a week after establishing the animal model. Echocardiography was used to evaluate heart structure and function. Intracardiac electric stimuli was used to analyze AF inducibility. Masson staining was used to evaluate the degree of atrial fibrosis. Ang-II-induced proliferation, migration, phenotypic switching and the capacity of extracellular matrix synthesis were examined after MSCs-Exo preconditioning. We reanalyzed two public expression datasets of MSCs-Exo and selected a few most highly expressed microRNAs. After literature search and experimental validation, we narrowed down our candidates to miR-148a-3p. Then, we predicted the potential target genes of miR-148a-3p, and determined ALK5 and SMAD2 as the targets of miR-148a-3p. Western blot was used to quantify Ang-II-induced protein expressions of TGF-β1/ALK5/SMAD2 pathway in fibroblasts after exposure to miR-148a-3p-rich MSCs-Exo.Results: Compared with mice in Ang-II group, mice in Ang-II+MSCs-Exo group showed less atrial enlargement, atrial fibrosis, a lower AF inducibility and AF duration. Ang-II-induced proliferation, migration, phenotypic switching, and capacity of extracellular matrix synthesis were ameliorated in fibroblasts after co-incubation with MSCs-Exo. After exposure to miR-148a-3p inhibitor, MSCs derived Exosomes (MSCs-148a-3p inhibitor-Exo) can significantly reverse above phenomenon. As the targets of miR-148a-3p, the expressions of ALK5 and Smad2 were lower in Ang-II+MSCs-Exo group compared with the Ang-II group. Furthermore, MSCs-Exo treatment inhibited Ang-II-induced activation of TGF-β1/ALK5/Smad2 pathway, and MSCs-148a-3p inhibitor -Exo reverse above phenomenon.Conclusions: MSCs-Exo can alleviate Ang-II induced atrial fibrosis and AF vulnerability through transferring miRNA-148a-3p to inhibit the activation of TGF-β1/ALK5/Smad2 pathway, providing a new avenue to AF treatment.

In the present experimental series, we have developed a novel nanocomposite to target activated macrophages in the colon with real time imaging and therapeutic capabilities. This binary nanocomposite was formed by the covalent conjugation of mannosylated NPs (Man-NPs) with carbon dots (CDs). Man-NPs were prepared using a self-assembly method based on mannosylated decamethylenediamine-grafted carboxymethyl inulin amphiphilic acid. While, the CDs were synthesized using a simple bottom-up process using citric acid monohydrate and diethylenetriamine, which were tightly bonded to the Man-NPs surface by carbodimide coupling. The resulting nanocomposite had a uniform size of 241.3 nm with a negative charge and a high drug casing density of 25.54 wt% and blue self-fluorescence were emitted. Whereas, in vitro observation of cellular uptake indicated the greater nanocomposite uptake in inflamed macrophage as compared to the untreated macrophage and mannose receptor-negative cell lines, 4T1 respectively. However, in vivo bio distribution exhibited a large number (60%) of CDs/Man-NPs nanocomposite accumulated in the inflamed colon of colitis mice. It should be noted that the novel nanocomposite, as macrophage-targeted drug delivery, could have promise for the treatment of inflammatory bowel disease (IBD).

The purpose of this study was to develop an oral nanocarrier as budesonide delivery system and to evaluate its therapeutic potential for inflammatory bowel disease (IBD). The nanoparticles (NPs) based on an amphiphilic inulin polymer with 4-aminothiophenol (ATP) grafted onto carboxymethyl inulin (CMI) were prepared. The particle sizes were about 210.18 nm and had the obvious pH/redox sensitive swelling transitions. The drug-release study of NPs in vitro showed a low release rate (about 45 wt%) in GSH-free media, whereas high release rate (about 80 wt%) in the media containing 20 mM GSH, exhibiting a redox-responsive property. Further in vivo experiments found the NPs tended to accumulate in inflamed sites, and exerted excellent therapeutic efficacy in comparison to drug suspension in colitis mice model. All the results demonstrated that the redox-sensitive NPs, based on amphiphilic inulin, may be used as colon-targeted drug delivery for the treatment of IBD.

Considering the phenomenon that most intelligent optimization algorithms easily plunge into local optimum when solving the complex problem of overlapping community detection, LFOCDA, an overlapping community detection algorithm based on Levy flight, is proposed in this paper. An extended modularity function has been used as the quality measurement standard of overlapping community division. During the iterative renewed process, Levy flight has been introduced owing to the variable-step random walk characteristic, so that the algorithm has a chance to jump out of local optimum, thus expanding the search range and guiding the search closer to global optimal solution. Enormous experimental results have verified the effectiveness and adaptability of the algorithm.

Community structure is considered to be one of the most important features of the real network. Community detection helps to understand the real construction of the network and can better analyze various complex systems. In this paper, five algorithms based on module degree optimization (GN, FN, CNM, Louvain, SML) are introduced. The ideas and design principles of this algorithms are introduced in detail, and the characteristics and advantages and disadvantages of each method are summarized. Finally, the prospect of this kind of algorithm is summarized.

As a basic feature of complex networks, community structure has gradually become a research hot spot. The community detection algorithm is helpful to analyze the real structure of the network. It is of great significance for the discovery of community, the analysis of community structure and function and the evolution and development of community. In this paper, these algorithms are analyzed and summarized, and some existing evaluation indicators of community detection algorithms are introduced. Finally, we look forward to the future research directions of complex networks community detection fields with some of my own recommendations.

T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORγt) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORγt itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORγt at its K81 residue. Knockdown of p300 downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells. In addition, p300 can promote RORγt-mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORγt and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORγt, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORγt-mediated transcriptional activation of IL-17.