Weilong Li

Microenvironment-responsive hydrogels present high potential in treating refractory wounds due to their capability of on-demand drug release. In this study, a specially designed hydrogel with smart targeting of refractory wound characteristics was designed to treat chronically infected diabetic wounds. Aminated gelatin reacted with oxidized dextran, forming a hydrogel cross-linked with a dynamic Schiff base, which is sensitive to the low-pH environment in refractory wounds. Nano-ZnO was loaded into the hydrogel for killing microbes. A Paeoniflorin-encapsulated micelle with a ROS-responsive property was fixed to the skeleton of the hydrogel via a Schiff base bond for low-pH- and ROS-stimulated angiogenic activity. The sequential responsiveness of the novel hydrogel enabled smart rescue of the deleterious microenvironment in refractory wounds. This highly biocompatible hydrogel demonstrated antibacterial and angiogenic abilities in vitro and significantly promoted healing of chronically infected diabetic wounds via sequential hemostatic, microbe killing, and angiogenic activities. This microenvironment-responsive hydrogel loaded with nZnO and Pf-encapsulated micelles holds great potential as a location-specific dual-response delivery platform for curing refractory, chronically infected diabetic wounds.

Motivation: Many studies have investigated the association between DNA methylation alterations and disease occurrences using two design paradigms, traditional case-control and disease-discordant twins. In the disease-discordant twin design, the affected twin serves as the case and the unaffected twin serves as the control. Theoretically the twin design takes advantage of controlling for the shared genetic make-up, but it is still highly debatable if and how much researchers may benefit from such a design over the traditional case-control design. Results: In this study, we investigate and compare the power of both designs with simulations. A liability threshold model was used assuming that identical twins share the same genetic contribution with respect to the liability of complex human diseases. Varying ranges of parameters have been used to ensure that the simulation is close to real-world scenarios. Our results reveal that the disease-discordant twin design implies greater statistical power over the traditional case-control design. For diseases with moderate and high heritability (>0.3), the disease-discordant twin design allows for large sample size reductions compared to the ordinary case-control design. Our simulation results indicate that the discordant twin design is indeed a powerful tool for epigenetic association studies. Availability and implementation: Computer scripts are available at https://github.com/zickyls/EWAS-Twin-Simulation. Supplementary information: Supplementary data are available at Bioinformatics online.

Abstract Depression is currently the leading cause of disability around the world. We conducted an epigenome-wide association study (EWAS) in a sample of 58 depression score-discordant monozygotic twin pairs, aiming to detect specific epigenetic variants potentially related to depression and further integrate with gene expression profile data. Association between the methylation level of each CpG site and depression score was tested by applying a linear mixed effect model. Weighted gene co-expression network analysis (WGCNA) was performed for gene expression data. The association of DNA methylation levels of 66 CpG sites with depression score reached the level of P < 1 × 10 −4 . These top CpG sites were located at 34 genes, especially PTPRN2 , HES5 , GATA2 , PRDM7 , and KCNIP1 . Many ontology enrichments were highlighted, including Notch signaling pathway, Huntington disease, p53 pathway by glucose deprivation, hedgehog signaling pathway, DNA binding, and nucleic acid metabolic process. We detected 19 differentially methylated regions (DMRs), some of which were located at GRIK2 , DGKA , and NIPA2 . While integrating with gene expression data, HELZ2 , PTPRN2 , GATA2 , and ZNF624 were differentially expressed. In WGCNA, one specific module was positively correlated with depression score ( r = 0.62, P = 0.002). Some common genes (including BMP2 , PRDM7 , KCNIP1 , and GRIK2 ) and enrichment terms (including complement and coagulation cascades pathway, DNA binding, neuron fate specification, glial cell differentiation, and thyroid gland development) were both identified in methylation analysis and WGCNA. Our study identifies specific epigenetic variations which are significantly involved in regions, functional genes, biological function, and pathways that mediate depression disorder.

Aim: Many efforts have been deployed to identify genetic variants associated with BMI. Alternatively, we explore epigenetic contribution to BMI variation by focusing on long noncoding RNAs (lncRNAs) which represents a key layer of epigenetic control. Materials & methods: We analyzed lncRNA expression in whole blood of 229 monozygotic twin pairs in association with BMI using generalized estimating equations. Results & conclusion: Six lncRNA probes were identified as significant (false discovery rate <0.05), with BMI showing causal effects on the expression of the significant lncRNAs. Functional annotation of differential profiles identified Gene ontology biological processes including kidney development, regulations of lipid biosynthetic process, circadian rhythm, notch signaling, etc. Whole blood lncRNAs are significantly expressed in response to BMI variation.