The Association Between Serum Palmitic Acid and Thyroid Function.

Aim: Emerging evidence indicates that palmitic acid (PA) can regulate the progression and development of many diseases. However, the studies examining the association between PA and thyroid function remain sparse. We aimed to investigate the association between serum PA (sPA) and thyroid function in the US population. Methods: In this retrospective study, a cross-sectional analysis was performed using the data pooled from the database of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2012. The thyroid parameters investigated were mainly free triiodothyronine (FT3), free thyroxine (FT4), total T3 (TT3), TT4, thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-thyroglobulin antibody (TgAb), and anti-thyroperoxidase antibody (TPOAb). The central sensitivity to thyroid function was evaluated by the thyroid feedback quantile-based index (TFQI), thyrotrophin thyroxine resistance index (TT4RI), and thyrotropin index (TSHI). The FT3 to FT4 ratio (FT3/FT4) was employed to evaluate peripheral sensitivity to thyroid hormones. Multiple imputation was applied to handle the missing data, and weighted multivariable linear regression, subgroup, and interaction analyses were then employed to estimate the association between sPA and thyroid parameters. Results: In the 737 adults, after adjusting covariates, we demonstrated a significant negative association between sPA and FT4 [ß = -1.078, 95% confidence interval (CI): -1.729 to -0.427], as well as a positive relationship between sPA and FT3/FT4 ratio (ß = 0.073, 95% CI: 0.044 to 0.102). These results did not change on multiple imputations. In the subgroup analyses, the associations were more significant in male and obese subjects. Conclusion: This investigation demonstrated the significant correlation between sPA and thyroid dysfunction, which suggested the close relationship between lipotoxicity and hypothyroidism or subclinical hypothyroidism. Future research is required to confirm these findings.

"Drug-Carrier" Synergy Therapy for Amyloid-ß Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly.

Amyloid-ß (Aß) toxicity is considered to be companioned by Tau phosphorylation in Alzheimer's disease (AD). The clinical AD therapy is usually subjected to low blood-brain barrier (BBB) penetration and complex interaction mechanisms between Aß and phosphorylated Tau. A "Drug-Carrier" synergy therapy is herein designed to simultaneously target Aß and Tau-associated pathways for AD treatment. To imitate natural nanoparticle configuration, the endogenous apolipoprotein A-I and its mimicking peptide 4F fused angiopep-2 (Ang) are sequentially grafted onto lipid nanocomposite (APLN), providing liberty of BBB crossing and microglia targeted Aß clearance. For synergy treatment, methylene blue (MB) is further assembled into APLN (APLN/MB) for Tau aggregation inhibition. After intravenous administration, the optimized density (5 wt%) of Ang ligands dramatically enhances APLN/MB intracerebral shuttling and accumulation, which is 2.15-fold higher than that Ang absent-modification. The site-specific release of MB collaborates APLN to promote Aß capture for microglia endocytosis clearance and reduce p-Tau level by 25.31% in AD pathogenesis. In AD-Aß-Tau bearing mouse models, APLN/MB can relieve AD symptoms, rescue neuron viability and cognitive functions. Collectively, it is confirmed that "Drug-Carrier" synergy therapy of APLN/MB is a promising approach in the development of AD treatments.

Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy.

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a "one-step" modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) "sandwich". After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.

Sponge particulates for biomedical applications: Biofunctionalization, multi-drug shielding, and theranostic applications.

Sponge particulates have attracted enormous attention in biomedical applications for superior properties, including large porosity, elastic deformation, capillary action, and three-dimensional (3D) reaction environment. Especially, the tiny porous structures make sponge particulates a promising platform for drug delivery, tissue engineering, anti-infection, and wound healing by providing abundant reservoirs of broad surface and internal network for cargo shielding and shuttling. To control the sponge-like morphology and improve the diversity of drug loading, some optimized preparation techniques of sponge particulates have been developed, contributing to the simplified preparation process and improved production reproducibility. Bio-functionalized strategies, including target modification, cell membrane camouflage, and hydrogel of sponge particulates have been applied to modulate the properties, improve the performance, and extend the applications. In this review, we highlight the unique physical properties and functions, current manufacturing techniques, and an overview of spongy particulates in biomedical applications, especially in inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity. Moreover, the current challenges and prospects of sponge particulates are discussed rationally, providing an insight into developing vibrant fields of sponge particulates-based biomedicine.

Identification of core genes and outcome in gastric cancer using bioinformatics analysis.

Gastric cancer (GC) is a common malignant neoplasm of gastrointestinal tract. We chose gene expression profile of GSE54129 from GEO database aiming to find key genes during the occurrence and development of GC. 132 samples, including 111 cancer and 21 normal gastric mucosa epitheliums, were included in this analysis. Differentially expressed genes (DEGs) between GC patients and health people were picked out using GEO2R tool, then we performed gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plug-in was utilized to visualize protein-protein interaction (PPI) of these DEGs. There were 971 DEGs, including 468 up-regulated genes enriched in focal adhesion, ECM-receptor interaction and PI3K-Akt signaling pathway, while 503 down-regulated genes enriched in metabolism of xenbiotics and drug by cytochrome P450, chemical carcinogenesis, retinol metabolism and gastric acid secretion. Three important modules were detected from PPI network using MCODE software. Besides, Fifteen hub genes with high degree of connectivity were selected, including BGN, MMP2, COL1A1, and FN1. Moreover, the Kaplan-Meier analysis for overall survival and correlation analysis were applied among those genes. In conclusion, this bioinformatics analysis demonstrated that DEGs and hub genes, such as BGN, might promote the development of gastric cancer, especially in tumor metastasis. In addition, it could be used as a new biomarker for diagnosis and to guide the combination medicine of gastric cancer.