Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective    To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods    The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results    After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion    Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.

Objective To observe the changes of serum clara cell protein?16 ( CC?16 ) and monocyte chemotaxis protein?1 (MCP?1) level in patients with acute respiratory distress syndrome (ARDS) and to explore their relationship with the disease severity and prognosis of ARDS??Methods One hundred and fourteen patients with ARDS who were admitted to Changzhi People′s hospital from January 2017 to March 2018 were selected as the subjects??They were divided into mild group ( n＝37),moderate group (n＝41) and severe group ( n＝36) according to the severity of ARDS??Sixty healthy persons in out?patient examination were selected as control group??The survival situation of patients in 4 weeks were recorded,the patients were divided into survival group ( n＝65) and death group ( n＝49) according to their survival situation??The age,gender,body mass index (BMI),smoking history,acute physiology and acute physiology and chronic health evaluation II ( APACHE II) score,sequential organ failure assessment ( SOFA) score, serum CC?16 and MCP?1 level were analyzed in each group??The relationship between serum CC?16,MCP?1 level and disease and prognosis of patients with ARDS were analyzed??Results With the increase of disease severity,APACHE II score, SOFA score and serum CC?16, MCP?1 level in patients with ARDS were significantly increased??The differences were statistically significant ( F＝1 216??886,1 339??247,290??879, 417??262; all P＝0??000)??The APACHE II score,SOFA score and serum CC?16,MCP?1 levels in the death group were (22??13± 2??47) scores,( 15??09 ± 1??97) scores,( 23??85 ± 4??27) μg／L, ( 36??64 ± 5??21) ng／L respectively,which were significantly higher than those in the survival group (18??25±2??35) scores,(13??23 ±2??03) scores,(17??34±4??13) μg／L,(27??93±4??88) ng／L,the differences were statistically significant (t＝8??538,4??905,8??211,9??146;all P＝0??000)??Pearson correlation analysis showed that there was a positive correlation between serum CC?16 level and MCP?1 level in patients with ARDS ( r＝0??589, P ＝0??000)??Meanwhile,the CC?16,MCP?1 were positive correlation with APACHE II score,SOFA score and mortality (CC?16:r＝0??504,0??549,0??472;P＝0??000,0??000,0??012;MCP?1:r＝0??493,0??528,0??435;P＝0??006, 0??000,0??025)??APACHE II score ( OR＝3??083,95%CI:0??025－1??364,P＜0??05),CC?16 ( OR＝5??403, 95%CI:0??011－6??561, P＜0??05) and MCP?1 ( OR＝2??892, 95%CI: 0??034－1??619, P＜0??05) were all closely related to ARDS death??CC?16 independent detection, MCP?1 independent detection and the two combined detection predicted the under?curve area, sensitivity and specificity of ARDS patients with in 4 weeks were 0??830, 82??35% and 72??16%; 0??719, 79??25% and 72??19%; 0??866, 85??06% and 80??72%respectively??Conclusion CC?16,MCP?1 are abnormally high expression in serum of patients with ARDS, and its levels are closely related to the severity and prognosis of patients with ARDS??CC?16 combined with MCP?1 detection has high diagnostic value for patients with ARDS,which can be used as an effective index to judge the disease and prognosis of patients with ARDS??