In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

Serum and plasma contain abundant biological information that reflect the body’s physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases

A New Effective Narrowband Active Noise Control System for Accommodating Frequency Mismatch

Narrowband active noise control (NANC) has shown excellent performance in dealing with the low frequency periodic noise generated by rotating machines, such as fans, engines and power transformers. Accommodating large frequency mismatch (FM) and improving its tracking capability is required for the NANC system. The existence of FM influences the noise cancellation performance. In this paper, a frequency correction algorithm based on least mean p-power (LMP) combined with the autoregressive (AR) model is designed for the NANC system, which is simple and feasible, and has a good performance under a large step size. In the NANC system, the reference signal is handled by a delay unit and AR model, and the coefficients of the AR model are adjusted by the LMP algorithm, which fine-tunes the coefficients and offers the reference signals to the NANC system. The stability bounds for the step size parameter have also been derived in the mean sense. The designed mechanism converges fast and enhances the noise decrement. Extensive simulations are performed to demonstrate the superior performance of the proposed NANC in dealing with periodic noises

Giant piezoelectricity in oxide thin films with nanopillar structure

10.1126/science.abb3209SCIENCE3696501292-

The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin

A cytosolic role for the histone methyltransferase Ezh2 in regulating lymphocyte activation has been suggested, but the molecular mechanisms underpinning this extranuclear function have remained unclear. Here we found that Ezh2 regulated the integrin signaling and adhesion dynamics of neutrophils and dendritic cells (DCs). Ezh2 deficiency impaired the integrin-dependent transendothelial migration of innate leukocytes and restricted disease progression in an animal model of multiple sclerosis. Direct methylation of talin, a key regulatory molecule in cell migration, by Ezh2 disrupted the binding of talin to F-actin and thereby promoted the turnover of adhesion structures. This regulatory effect was abolished by targeted disruption of the interactions of Ezh2 with the cytoskeletal-reorganization effector Vav1. Our studies reveal an unforeseen extranuclear function for Ezh2 in regulating adhesion dynamics, with implications for leukocyte migration, immune responses and potentially pathogenic processes.NMRC (Natl Medical Research Council, S’pore)MOE (Min. of Education, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)Accepted versio