Peritoneal inflammation remains a major cause of treatment failure in patients with kidney failure who receive peritoneal dialysis. Peritoneal inflammation is characterized by an increase in neutrophil infiltration. However, the molecular mechanisms that control neutrophil recruitment in peritonitis are not fully understood. ELMO and DOCK proteins form complexes which function as guanine nucleotide exchange factors to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. In the current study, we found that deletion of the Elmo1 gene causes defects in chemotaxis and the adhesion of neutrophils. ELMO1 plays a role in the fMLP-induced activation of Rac1 in parallel with the PI3K and mTORC2 signaling pathways. Importantly, we also reveal that peritoneal inflammation is alleviated in Elmo1 knockout mice in the mouse model of thioglycollate-induced peritonitis. Our results suggest that ELMO1 functions as an evolutionarily conserved regulator for the activation of Rac to control the chemotaxis of neutrophils both in vitro and in vivo. Our results suggest that the targeted inhibition of ELMO1 may pave the way for the design of novel anti-inflammatory therapies for peritonitis.

Clustered regularly interspaced short palindromic repeats (CRISPR) molecular diagnostic technology is one of the most reliable diagnostic tools for infectious diseases due to its short reaction time, high sensitivity, and excellent specificity. However, compared with fluorescent polymerase chain reaction (PCR) technology, CRISPR molecular diagnostic technology lacks high-throughput automated instrumentation and standardized detection reagents for high sensitivity, limiting its large-scale clinical application. In this study, a high-throughput automated device was developed by combining reagent lyophilization, extraction-free technology, and a one-pot consumable system. This innovative approach enabled the rapid sample-in-result-out detection of 48 samples in 25 min and demonstrated high sensitivity and specificity for the qualitative analysis of clinical samples. The obtained results show that the detection limit of the designed system for African swine fever virus (ASFV) is 0.5 copies/μL. As a proof concept, a single-tube dual-target nucleic acid detection method was developed, achieving a detection limit of 5 copies/μL for the ORF1ab and N genes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 45 min. The method is highly specific, reliable, and stable, providing a feasible solution for the clinical application of CRISPR nucleic acid detection technology.

Acute myocardial infarction (AMI) is a rapidly progressing cardiovascular condition associated with high mortality. Myoglobin is an early biomarker of AMI; however, its detection using conventional methods is limited by complex workflows and low resistance to interference. In this study, we developed an integrated myoglobin detection platform that combined magneto-immunoassay with microfluidic technology. A giant magnetoresistance (GMR) sensor was fabricated using micro-electro-mechanical systems (MEMS). The designed microfluidic chip integrated sample pretreatment, immunoreaction, and magnetic signal capture functionalities. Its built-in GMR sensor, labeled with magnetic nanoparticles, directly converted the “antigen–antibody” biochemical signal into detectable magnetoresistance changes, thereby enabling the indirect detection of myoglobin. A magneto-immunoassay analysis system consisted of a fluidic drive, magnetic field control, and data acquisition functions. Various key parameters were optimized, including EDC/NHS concentration, antibody concentration, and magnetic bead size. Under the optimal conditions and using 1 μm magnetic beads as labels and an external detection magnetic field of 60 Oe, the platform successfully detected myoglobin at 75 ng/mL with ∆MR ≥ 0.202%. Specificity tests demonstrated that the platform had high specificity for myoglobin and could effectively distinguish myoglobin from bovine serum albumin (BSA) and troponin I. This study presents a rapid, accurate myoglobin detection platform that can be applied for the early diagnosis of AMI.