Integrative analysis of transcriptome and proteome in primary Sjögren syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immune-mediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. METHOD: Transcriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjögren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. RESULTS: As a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. CONCLUSION: Herein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

The Driving Waveform Design Method of Power-Law Fluid Piezoelectric Printing Based on Iterative Learning Control.

In some applications of piezoelectric three-dimensional inkjet printing, the materials used are power-law fluids as they are shear thinning. Their time-varying viscosities affect the droplet formation, which is determined by the volume flow rate at the nozzle outlet. To obtain a fine printing effect, it is necessary to present a driving waveform design method that considers the shear-thinning viscosities of materials to control the volume flow rate at the nozzle outlet, which lays the foundation for the single and stable droplet generation during the printing process. In this research, we established the relationship between the driving waveform and the volume flow rate at the nozzle outlet by modifying a model that describes the inkjet mechanism of power-law fluid. The modified model was used to present a driving waveform design method based on iterative learning control. The iterative learning law of the method was designed based on the gradient descent algorithm and demonstrated its convergence. The driving waveform design method was verified to be practical and feasible by implementing drop generation experiments.

Additive Manufacturing for Terahertz Metamaterials on the Dielectric Surface based on Optimized Electrohydrodynamic Drop-on-demand Printing Technology.

The conventional techniques used to fabricate terahertz metamaterials, such as photolithography and etching, face hindrances in the form of high costs, lengthy processing cycles, and environmental pollution. In contrast, electrohydrodynamic (EHD) drop-on-demand (DOD) printing technology holds promise as an additive manufacturing method capable of producing micrometer- and nanometer-scale patterns rapidly and cost-effectively. However, achieving stable large-area printing proves challenging due to issues related to charge accumulation in insulated substrates and inconsistent meniscus vibration. In this paper, a smooth bipolar waveform driving method is proposed aimed at solving the problems of charge accumulation on insulated substrates and poor print consistency. The method involves utilizing driving waveforms with opposite polarities for neighboring droplets, allowing the charges carried by the printed droplets to neutralize each other. Moreover, extending the duration of the high voltage rise and fall times enhances the consistency of meniscus motion, thereby improving the stability of printing. Through optimization of the printing parameters, droplets with a diameter of 1.37 µm and straight lines with a width of 3 µm were printed. Furthermore, this approach was employed to print terahertz metamaterial surface devices, and the performance of the metamaterial is in good agreement with the simulation results. These findings demonstrate that the method greatly improves the stability of EHD DOD printing, thereby advancing the application of the technology in additive processing at the micro- and nanoscale.

Immune infiltration analysis reveals immune cell signatures in salivary gland tissue of primary Sjögren's syndrome.

Introduction: Mouse models are the basis for primary Sjögren's syndrome (pSS) research. However, the depth of comparisons between mice and humans in salivary gland (SG) immune cells remains limited. Methods: The gene expression profiles of SGs from normal subjects and pSS patients were downloaded from the Gene Expression Comprehensive Database. The proportion of infiltrating immune cell subsets was then assessed by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT). An experimental Sjögren's syndrome (ESS) mouse model was successfully constructed using SG protein. Based on mouse SG tissue RNA-Seq data, the seq-ImmuCC model was used to quantitatively analyze the compositional ratios of 10 immune cells in pSS patients and mouse model SG tissues. Results: Computed and obtained 31 human data samples using the CIBERSORT deconvolution method. The immune cell infiltration results showed that, compared to normal human SG tissue, the content of gamma delta T cells was significantly different from naive CD4+ T cells and significantly increased, while the plasma cell content decreased. Principal component analysis indicated differences in immune cell infiltration between pSS patients and normal subjects. Meanwhile, for ESS model mouse data analysis, we found that the proportion of macrophages increased, while the proportion of CD4+ T cells, B cells, and monocytes decreased. Furthermore, we found that the proportion of monocytes was decreased, while the proportion of macrophages was increased in the SG tissues of pSS patients and model mice. The infiltration of CD4+ T, CD8+ T, and B cells also showed some differences. Discussion: We comprehensively analyzed SG immune infiltration in pSS patients and model mice. We demonstrated conserved and nonconserved aspects of the immune system in mice and humans at the level of immune cells to help explain the primary regulation of immune mechanisms during the development of Sjögren's syndrome.

Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer malignancy worldwide and is known to have poor prognosis. The pathogenesis behind the development of HNSCC is not fully understood. Modifications on RNA are involved in many pathophysiological processes, such as tumor development and inflammation. Adenosine-related RNA modifications have shown to be linked to cancer and may play a role in cancer occurrence and development. To date, there are at least 170 different chemical RNA modifications that modify coding and non-coding RNAs (ncRNAs). These modifications affect RNA stability and transcription efficiency. In this review, we focus on the current understanding of the four major RNA adenosine modifications (N6-Methyladenosine, N1-Methyladenosine, Alternative Polyadenylation Modification and A-to-I RNA editing) and their potential molecular mechanisms related to HNSCC development and progression. We also touch on how these RNA modifications affect treatment of HNSCCs.