Microneedle-mediated nanomedicine to enhance therapeutic and diagnostic efficacy.

Nanomedicine has been extensively explored for therapeutic and diagnostic applications in recent years, owing to its numerous advantages such as controlled release, targeted delivery, and efficient protection of encapsulated agents. Integration of microneedle technologies with nanomedicine has the potential to address current limitations in nanomedicine for drug delivery including relatively low therapeutic efficacy and poor patient compliance and enable theragnostic uses. In this Review, we first summarize representative types of nanomedicine and describe their broad applications. We then outline the current challenges faced by nanomedicine, with a focus on issues related to physical barriers, biological barriers, and patient compliance. Next, we provide an overview of microneedle systems, including their definition, manufacturing strategies, drug release mechanisms, and current advantages and challenges. We also discuss the use of microneedle-mediated nanomedicine systems for therapeutic and diagnostic applications. Finally, we provide a perspective on the current status and future prospects for microneedle-mediated nanomedicine for biomedical applications.

4D Multimaterial Printing of Soft Actuators with Spatial and Temporal Control.

Soft actuators (SAs) are devices which can interact with delicate objects in a manner not achievable with traditional robotics. While it is possible to design a SA whose actuation is triggered via an external stimulus, the use of a single stimulus creates challenges in the spatial and temporal control of the actuation. Herein, a 4D printed multimaterial soft actuator design (MMSA) whose actuation is only initiated by a combination of triggers (i.e., pH and temperature) is presented. Using 3D printing, a multilayered soft actuator with a hydrophilic pH-sensitive layer, and a hydrophobic magnetic and temperature-responsive shape-memory polymer layer, is designed. The hydrogel responds to environmental pH conditions by swelling or shrinking, while the shape-memory polymer can resist the shape deformation of the hydrogel until triggered by temperature or light. The combination of these stimuli-responsive layers allows for a high level of spatiotemporal control of the actuation. The utility of the 4D MMSA is demonstrated via a series of cargo capture and release experiments, validating its ability to demonstrate active spatiotemporal control. The MMSA concept provides a promising research direction to develop multifunctional soft devices with potential applications in biomedical engineering and environmental engineering.

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis.

Background: Both obesity (OB) and periodontitis (PD) are chronic non-communicable diseases, and numerous epidemiological studies have demonstrated the association between these two diseases. However, the molecular mechanisms that could explain the association between OB and PD are largely unclear. This study aims to investigate the common gene signatures and biological pathways in OB and PD through bioinformatics analysis of publicly available transcriptome datasets. Methods: The RNA expression profile datasets of OB (GSE104815) and PD (GSE106090) were used as training data, and GSE152991 and GSE16134 as validation data. After screening for differentially expressed genes (DEGs) shared by OB and PD, gene enrichment analysis, protein-protein interaction (PPI) network construction, GeneMANIA analysis, immune infiltration analysis and gene set enrichment analysis (GSEA) were performed. In addition, receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the hub gene. Finally, we constructed the hub gene-associated TF-miRNA-mRNA regulatory network. Results: We identified a total of 147 DEGs shared by OB and PD (38 down-regulated and 109 up-regulated). Functional analysis showed that these genes were mainly enriched in immune-related pathways such as B cell receptor signalling, leukocyte migration and cellular defence responses. 14 hub genes (FGR, MNDA, NCF2, FYB1, EVI2B, LY86, IGSF6, CTSS, CXCR4, LCK, FCN1, CXCL2, P2RY13, MMP7) showed high sensitivity and specificity in the ROC curve analysis. The results of immune infiltration analysis showed that immune cells such as macrophages, activated CD4 T cells and immune B cells were present at high infiltration levels in both OB and PD samples.The results of GeneMANIA analysis and GSEA analysis suggested that five key genes (FGR, LCK, FYB1, LY86 and P2RY13) may be strongly associated with macrophages. Finally, we constructed a TF-miRNA-mRNA regulatory network consisting of 233 transcription factors (TFs), 8 miRNAs and 14 mRNAs based on the validated information obtained from the database. Conclusions: Five key genes (FGR, LCK, FYB1, LY86, P2RY13) may be important biomarkers of OB and PD. These genes may play an important role in the pathogenesis of OB and PD by affecting macrophage activity and participating in immune regulation and inflammatory responses.

Assembly of Fillable Microrobotic Systems by Microfluidic Loading with Dip Sealing.

Microrobots can provide spatiotemporally well-controlled cargo delivery that can improve therapeutic efficiency compared to conventional drug delivery strategies. Robust microfabrication methods to expand the variety of materials or cargoes that can be incorporated into microrobots can greatly broaden the scope of their functions. However, current surface coating or direct blending techniques used for cargo loading result in inefficient loading and poor cargo protection during transportation, which leads to cargo waste, degradation and non-specific release. Herein, a versatile platform to fabricate fillable microrobots using microfluidic loading and dip sealing (MLDS) is presented. MLDS enables the encapsulation of different types of cargoes within hollow microrobots and protection of cargo integrity. The technique is supported by high-resolution 3D printing with an integrated microfluidic loading system, which realizes a highly precise loading process and improves cargo loading capacity. A corresponding dip sealing strategy is developed to encase and protect the loaded cargo whilst maintaining the geometric and structural integrity of the loaded microrobots. This dip sealing technique is suitable for different materials, including thermal and light-responsive materials. The MLDS platform provides new opportunities for microrobotic systems in targeted drug delivery, environmental sensing, and chemically powered micromotor applications.

Characterization of a novel affinity binding ligand for tyrosine nitrated peptides from a phage-displayed peptide library.

As an important post-translational modification in response to oxidative and nitrosative stress, protein tyrosine nitration is deeply involved in many physiological and pathological processes. Identifying tyrosine nitration in proteins is challenging due to its low abundance.Consequently, pre-separation and enrichment of tyrosine-nitrated peptides (TNPs) are necessary before submitting them to mass spectrometry analysis. However, the most popularly used anti-nitrotyrosine antibody pull-down method showed limitations like sequence preference and unspecific binding. Therefore, developing novel affinity purification materials for TNPs is of significance. In the present study, we screened the phage-displayed 12-mer randomized peptide library for affinity binding peptide of the synthetic standard TNP (sTNP, sequence: H2N-GGGGY*GGG-COOH) and identified a peptide named NT-1 (H2N-TLWPFDLWLKTR-COOH) as a promising candidate. NT-1 at extremely low concentration (3 nM) in solutions could be efficiently captured by immobilized sTNP as determined by pull-down and subsequent MALDI-TOF MS analysis. Surface plasmon resonance (SPR) measurement confirmed that NT-1 possesseed a good selectivity, showing more than 100-fold higher binding affinity with TNP than its non-nitrated counterpart. Moreover, NT-1 could efficiently capture various types of TNPs in solutions even in the presence of 1000-fold excessive amount of trypsinized BSA fragments. Most importantly, NT-1 showed superiority to commercially used nitrotyrosine antibody as the former captured more TNPs, with less sequence preference. In summary, our study provided NT-1 as a novel affinity binding ligand for TNPs and should be useful in developing an alternative enrichment strategy for TNPs.