Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Nocardia is a Gram-positive pathogen responsible for causing dairy mastitis,which leads to purulent granulomatous lesions in mammary tissue and can significantly impact the dairy indus-try,resulting in substantial economic losses.To develop a rapid and accurate diagnostic method for detecting Nocardia of bovine origin,a conserved sequence of the 16S rRNA gene from Nocardia was selected from the NCBI database.Based on this sequence,a pair of primers and a TaqMan fluo-rescent quantitative probe were designed.The validation of the TaqMan fluorescence quantitative PCR(qPCR)method found in this study showed that the Ctvalue had a good linear relationship with recombinant plasmid concentrations ranging from 1×1010 to 1×102 copies/μL,with a regres-sion equation of y=-3.536x+43.78,a correlation coefficient(R2)of 0.997 5,a slope of-3.536,and an amplification efficiency(E)of 91％(where 90％＜E＜110％).The specificity was strong,with no cross-reactions with other pathogens.The standard curve had a high sensitivity with a low-er detection limit of 1 × 102 copies/μL,it was 100-fold higher than conventional PCR.The repeatability of the standard curve was also good.Both intra-and inter-group coefficients of varia-tion were below 2％.Using this method,234 milk samples and 80 environmental samples were tested using this method,respectively,with a positive detection rate of 27.07％,whereas conven-tional PCR had a positive detection rate of 19.43％,indicating that this method was more sensitive compared to conventional PCR.The fluorescent quantitative PCR detection method established in this study provides an effective means for the clinical detection of Nocardia in dairy cows.

Nocardia is a Gram-positive pathogen responsible for causing dairy mastitis,which leads to purulent granulomatous lesions in mammary tissue and can significantly impact the dairy indus-try,resulting in substantial economic losses.To develop a rapid and accurate diagnostic method for detecting Nocardia of bovine origin,a conserved sequence of the 16S rRNA gene from Nocardia was selected from the NCBI database.Based on this sequence,a pair of primers and a TaqMan fluo-rescent quantitative probe were designed.The validation of the TaqMan fluorescence quantitative PCR(qPCR)method found in this study showed that the Ctvalue had a good linear relationship with recombinant plasmid concentrations ranging from 1×1010 to 1×102 copies/μL,with a regres-sion equation of y=-3.536x+43.78,a correlation coefficient(R2)of 0.997 5,a slope of-3.536,and an amplification efficiency(E)of 91％(where 90％＜E＜110％).The specificity was strong,with no cross-reactions with other pathogens.The standard curve had a high sensitivity with a low-er detection limit of 1 × 102 copies/μL,it was 100-fold higher than conventional PCR.The repeatability of the standard curve was also good.Both intra-and inter-group coefficients of varia-tion were below 2％.Using this method,234 milk samples and 80 environmental samples were tested using this method,respectively,with a positive detection rate of 27.07％,whereas conven-tional PCR had a positive detection rate of 19.43％,indicating that this method was more sensitive compared to conventional PCR.The fluorescent quantitative PCR detection method established in this study provides an effective means for the clinical detection of Nocardia in dairy cows.

Objective To investigate the effects of hypoxic preconditioning on learning and memory and the possible protective mechanism in mice with cerebral ischemia-reperfusion injury.Methods Healthy adult male Kunming mice were randomly divided into five groups by Random number table:normal group( N group),hypoxic preconditioning group (HPC group),sham operation group (C group),ischemia-reperfusion group(O group),hypoxic preconditioning and ischemia-reperfusion group(HPC+O group).HPC+O group were given hypoxic preconditioning before 24h of ischemia-reperfusion.The escape latency was detected by Morris water maze and the neuron apoptosis of CA 1 area of hippocampal was determined by immunofluores-cence techniqueR.e sults The escape latency in HPC+O group on the second,third and fourth day of MWM was (39.92±4.52)s,(30.98±2.44)s,(19.69±4.27)s,and significantly lower than that in O group((54.35± 3.66)s,(46.31±4.81)s,(36.81±3.86)s).Mice in HPC+O spent longer time in the target quadrant than that in O group((36.44±5.33)%and(24.5±2.59)%,respectively, P<0.05).Immunofluorescence showed that the apoptotic ration of nerve cells in hippocampal CA 1 was significantly lower than that in O group ( 11.7 ± 0.14 and 1.35±0.14, P<0.05).Conclusion Hypoxic preconditioning can increase hippocampal CA1 neurons hypoxia tolerance of ischemia reperfusion injury in mice,and reduce the incidence of neural cell apoptosis.