From "wanting to exercise" to "sticking with exercise": motivational profiles and configurational pathways to high exercise adherence among college students-an LPA and fsQCA analysis.

Ulcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colonic mucosa, classified as a subtype of inflammatory bowel disease (IBD) []. The primary symptoms of UC patients are recurrent bloody stools and diarrhea, which can be life-threatening in severe cases, often requiring long-term or lifelong medication []. The pathogenesis of UC is multifaceted, involving genetic alterations, intestinal immune system imbalance, particularly mucosal immune dysregulation, and environmental factors []. Epidemiological data indicate that UC can be diagnosed at any age, with peak incidence in young adults (20–49 years in China), showing no significant gender differences. Globally, the incidence and prevalence of UC have steadily risen in parallel with the progression of industrialization []. In the past 20 years, the incidence and prevalence of UC have markedly increased in China [], Approximately 10 % of UC patients are diagnosed before the age of 20 [], with the disease imposing significant economic burdens on families and society, while also severely impacting patients’ mental health and quality of life []. Proteomics plays a critical role in elucidating disease mechanisms and identifying potential therapeutic targets. In previous proteomics research, immunoglobulin G (IgG) and IgA1 have been identified as plasma proteins closely associated with UC disease activity []. IgA is also considered a potential glycoprotein target, as its glycosylation may affect FcαR receptor binding and trigger pro-inflammatory or anti-inflammatory responses, serving as a diagnostic biomarker []. MR was initially developed as an alternative to randomized controlled trials (RCTs), using genetic instruments instead of the traditional exposure-disease paradigm. According to Mendelian genetics, genetic information is randomly allocated at conception, preceding the onset of any disease manifestations and thereby reducing confounding bias []. However, the causal role of plasma protein ratios (versus individual proteins) in UC pathogenesis remains unclear, and no studies have systematically distinguished truly causal biomarkers from secondary inflammatory phenomena. To address these gaps, we conducted the first large-scale Mendelian randomization study analyzing 2,821 plasma protein ratios, followed by single-cell sequencing validation to pinpoint mucosa-specific protein network dysregulation. Crucially, we further evaluated the diagnostic potential of the prioritized DLL1/TGFBR2 ratio through clinical cohort assays, establishing a translational pipeline from genetic inference to biomarker discovery.