Integrative genetic and multi-omics analysis reveals the interleukin-6 receptor’s role in recurrent spontaneous abortion

BackgroundRecurrent spontaneous abortion (RSA) significantly impacts women’s health, yet the underlying biological mechanisms remain poorly defined. Understanding the molecular contributors to RSA is crucial for developing targeted interventions.ObjectiveThis study aims to investigate the causal relationships between plasma proteins and RSA, focusing on the identification of potential therapeutic targets through multi-omic approaches.MethodsWe utilized two-sample Mendelian randomization (MR) analyses integrating genome-wide association study (GWAS) data for both plasma proteins and RSA. Proteomic data were sourced from the UK Biobank-Plasma Proteome Project and deCODE Health Study. We further validated our findings through both bulk and single-cell RNA sequencing of clinical specimens, alongside quantitative real-time polymerase chain reaction and immunohistochemistry. A phenome-wide association study was also conducted to assess the safety and broader implications of identified targets.ResultsOur analyses identified the interleukin 6 receptor (IL6R) as a key candidate, with elevated plasma levels correlating with increased RSA risk. Furthermore, IL6R was found to be upregulated in RSA-related endometrial and decidual tissues. The phenome-wide association study provided insights into potential side effects and additional therapeutic indications for IL6R.ConclusionIL6R upregulation is mechanistically implicated in the pathogenesis of RSA, establishing it as a validated causal biomarker and a potentially actionable therapeutic target. This study not only highlights the role of IL6R in RSA but also supports its development into a therapeutic strategy with a comprehensive safety profile

Adaptive Bit-Labeling Design for Probabilistic Shaping Based on Residual Source Redundancy

By using the residual source redundancy to achieve the shaping gain, a joint source-channel coded modulation (JSCCM) system has been proposed as a new solution for probabilistic amplitude shaping (PAS). However, the source and channel codes in the JSCCM system should be designed specifically for a given source probability to ensure optimal PAS performance, which is undesirable for systems with dynamically changing source probabilities. In this paper, we propose a new shaping scheme by optimizing the bit-labeling of the JSCCM system. Instead of the conventional fixed labeling, the proposed bit-labelings are adaptively designed according to the source probability and the source code. Since it is simple to switch between different labelings according to the source probability and the source code, the proposed design can be considered as a promising low complexity alternative to obtain the shaping gain for sources with different probabilities. Numerical results show that the proposed bit-labelings can significantly improve the bit-error rate (BER) performance of the JSCCM system