Helicobacter pylori (H. pylori) has infected more than half of the world’s population and is still a threat to human health. The urea breath test, despite being widely used in clinical diagnosis, still faces huge challenges in the immediate detection of H. pylori. Thus, a rapid, sensitive, and highly specific point of care diagnosis is particularly important for preventing the further transmission of H. pylori and for real-time monitoring of the disease in a given population. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have been applied to various types of nucleic acid testing; however, there are often shortcomings of complex operation and high signal transmission background. In this study, we proposed a new platform for the assay of H. pylori using one-tube-based CRISPR/Cas12a diagnostic methods and designed a detector for this platform, which is a portable array detector for visible analysis of thermostatic nucleic acid amplification (Pad-VATA). By incorporating isothermal recombinase polymerase amplification, our platform could detect the conserved gene fragments of H. pylori with a constant low as 2 copies/μl. The assay process can be performed at a single temperature in about 30 min and integrated into the reactor in the palm-sized Pad-VATA to facilitate rapid diagnosis of H. pylori. We also verified the accuracy of our platform using 10 clinical samples and found that the platform can quickly detect H. pylori infection in a given population. We believe that this fast, convenient, efficient, and inexpensive screening and diagnostic platform can be widely used in various settings, including homes and clinics.

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis. Mitochondrial oxidative capacity and metabolites profiling analysis show that MOTS-c significantly reverses NASH-induced mitochondrial metabolic deficiency. Moreover, we identify that MOTS-c directly interacts with the BH3 domain of antiapoptotic B cell lymphoma-2 (Bcl-2), increases Bcl-2 protein stability, and suppresses Bcl-2 ubiquitination. By using a Bcl-2 inhibitor or adeno-associated virus (AAV)-mediated Bcl-2 knockdown, we further confirm that MOTS-c improves NASH-induced mitochondrial dysfunction, inflammation, and fibrosis, which are dependent on Bcl-2 function. Therefore, our findings show that MOTS-c is a potential therapeutic agent to inhibit the progression of NASH.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (BSIs-CRKP) are associated with high mortality rates, necessitating early risk stratification tools. This study aimed to identify risk factors and develop a nomogram model to predict BSIs-CRKP in hospitalized patients. A single-center retrospective case-control study was conducted at Shaanxi Provincial People’s Hospital (2017–2024). Patients with Klebsiella pneumoniae bacteremia were stratified into CRKP (n = 154) and carbapenem-susceptible (CSKP, n = 233) groups. Clinical data, including demographics, comorbidities, treatments, and antimicrobial exposure, were analyzed. Risk factors were identified via multivariate logistic regression, and a nomogram model was developed using R software. Model performance was evaluated using ROC curves, calibration plots, and the Hosmer-Lemeshow test. Independent risk factors for BSIs-CRKP included indwelling urinary catheterization (OR = 2.531, P = 0.038), central venous catheterization (OR = 2.673, P = 0.015), immunosuppressant use (OR = 3.782, P = 0.006), carbapenem exposure (OR = 4.470, P < 0.001), and age ≥ 65 years (OR = 3.740, P = 0.002). A nomogram model was constructed based on these risk factors, which demonstrated good predictive performance with an area under the curve (AUC) of 0.878 (95% CI: 0.845–0.910) and exhibited excellent calibration (Hosmer-Lemeshow, P = 0.234). This nomogram model effectively stratifies BSIs-CRKP risk using five clinically accessible variables. External validation and integration of genomic data are warranted to enhance generalizability and precision.