Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To explore the key components and mechanism of Qufeng Ningfei Powder in treating asthma through qualitative analysis of its blood components, combined with network pharmacology and molecular docking techniques.Methods:The blood components of Qufeng Ningfei Powder were qualitatively analyzed using UPLC-QE-Orbitrap-MS technology. R language was employed to analyze chip data from the GEO database, obtaining a list of differentially expressed genes. SwissTargetPrediction was utilized to predict the targets of drug components. Asthma-related targets were searched through databases such as OMIM, GeneCards, and TTD. The intersection of drug and disease targets was identified using Venn online analysis tool, constructing a "drug-component-target-disease" network to screen potential core components. A protein-protein interaction network (PPI) of core targets was constructed using STRING platform and Cytoscape software. GO function enrichment and KEGG pathway analysis were conducted using DAVID database to validate potential mechanism. Molecular docking was performed to verify the interaction between key components and core targets.Results:A total of 64 components were identified, from which 53 active components were screened, corresponding to 609 targets. Further searching disease databases revealed 96 target genes related to asthma, with an intersection of 6 genes between drug and asthma differential genes. Core target gene IL6 and its corresponding core compound were determined through network topology analysis. Molecular docking confirmed the binding of the main active components of Qufeng Ningfei Powder with the core target protein IL6.Conclusion:The blood components of Qufeng Ningfei Powder may regulate IL-17 through IL6, counteract airway remodeling, oxidative stress, and airway hyperresponsiveness, and thus treat asthma.

OBJECTIVE T o establish a simple,rapid,highly sensitive and highly specific visualized detection meth-od for Klebsiella pneumoniae based on recombinase polymerase amplification(RPA)technique combined with the lateral flow dipstick(LFD)technique.METHODS The specific primers targeting the khe gene of K.pneumoniae were designed for RPA,the reaction temperature and reaction time for RPA were optimized,the optimal experi-mental conditions for the LFD were determined based on the colorimetric results.The sensitivity,stability,speci-ficity and clinical practicability of RPA-LFD in detection of the K.pneumoniae were evaluated.RESULTS RPA could achieved the optimal detection result for simplification of K.pneumoniae at 34 ℃ for 10 min.The LFD showed the best color development when Milipore HF 135s was used as the nitrocellulose membrane,phosphate buffered saline containing Tween-20(PBST)was used as the sample developing solution,and the concentrations of streptavidin and secondary antibody were 0.8 mg/ml and 0.1 mg/ml,respectively.The detection limit of the RPA-LFD was 5 CFU/ml for detection of K.pneumoniae,the relative standard deviation of the band color inten-sity was less than 5％in six parallel experiments,and there was no cross reactions with other bacterial strains.In addition,the sensitivity of the RPA-LFD in detection of K.pneumoniae was not affected by the serum compo-nents such as proteins and lipids.CONCLUSION The rapid detection method for K.pneumoniae that is established based RPA-LFD is characterized by the simple operation,high sensitivity and high specificity,and it does not need complicated equipment or strict technical requirement for operators and provides a new technique for early diagno-sis and epidemiological survey of the K.pneumoniae.

Objective:To analyze the key β-amyloid protein (Aβ) deposition in brain regions affecting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).Methods:Based on the positron emission tomography data of Aβ in the Alzheimer's disease neuroimaging initiative database, the penalized generalized estimating equation (PGEE) and the mixed effects regression forest algorithm (MERF) were used to conduct dimensionality reduction analysis on 164 brain regions with Aβ deposition. Additionally, a multivariate longitudinal data joint model was used to screen the key Aβ deposition brain regions that influence the progression from MCI to AD.Results:Five key brain regions were commonly screened out by the PGEE and MERF models, they were the right prefrontal orbital cortex, the left superior temporal sulcus shore cortex, the right medial orbitofrontal cortex, the left putamen, and the right transverse temporal cortex, respectively. The results of the multivariate longitudinal data joint model based on these 5 Aβ deposition brain regions showed that, except the left superior temporal sulcus shore cortex, the longitudinal change trajectories of the other 4 Aβ deposition brain regions all affected the progression from MCI to AD ( P<0.05). Conclusion:The Aβ deposition in the right prefrontal orbital cortex, right medial orbitofrontal cortex, left putamen and right transverse temporal cortex affect the progression from MCI to AD.

The construction,renovation,and expansion of general hospitals involve numerous infection control issues,including zoning,flow line design,and air flow direction.Although relevant regulations have specified infection control require-ments for hospital architectural design,infection control professionals often struggle to provide planning and design recommenda-tions from a professional perspective due to the lack of integrated guidelines.Based on this,this article summarizes the standards and key issues that should be considered during the planning and design of critical departments in general hospitals,aiming to provide reference for infection control professionals.

The construction,renovation,and expansion of general hospitals involve numerous infection control issues,including zoning,flow line design,and air flow direction.Although relevant regulations have specified infection control require-ments for hospital architectural design,infection control professionals often struggle to provide planning and design recommenda-tions from a professional perspective due to the lack of integrated guidelines.Based on this,this article summarizes the standards and key issues that should be considered during the planning and design of critical departments in general hospitals,aiming to provide reference for infection control professionals.

Objective:To analyze the key β-amyloid protein (Aβ) deposition in brain regions affecting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).Methods:Based on the positron emission tomography data of Aβ in the Alzheimer's disease neuroimaging initiative database, the penalized generalized estimating equation (PGEE) and the mixed effects regression forest algorithm (MERF) were used to conduct dimensionality reduction analysis on 164 brain regions with Aβ deposition. Additionally, a multivariate longitudinal data joint model was used to screen the key Aβ deposition brain regions that influence the progression from MCI to AD.Results:Five key brain regions were commonly screened out by the PGEE and MERF models, they were the right prefrontal orbital cortex, the left superior temporal sulcus shore cortex, the right medial orbitofrontal cortex, the left putamen, and the right transverse temporal cortex, respectively. The results of the multivariate longitudinal data joint model based on these 5 Aβ deposition brain regions showed that, except the left superior temporal sulcus shore cortex, the longitudinal change trajectories of the other 4 Aβ deposition brain regions all affected the progression from MCI to AD ( P<0.05). Conclusion:The Aβ deposition in the right prefrontal orbital cortex, right medial orbitofrontal cortex, left putamen and right transverse temporal cortex affect the progression from MCI to AD.

OBJECTIVE T o establish a simple,rapid,highly sensitive and highly specific visualized detection meth-od for Klebsiella pneumoniae based on recombinase polymerase amplification(RPA)technique combined with the lateral flow dipstick(LFD)technique.METHODS The specific primers targeting the khe gene of K.pneumoniae were designed for RPA,the reaction temperature and reaction time for RPA were optimized,the optimal experi-mental conditions for the LFD were determined based on the colorimetric results.The sensitivity,stability,speci-ficity and clinical practicability of RPA-LFD in detection of the K.pneumoniae were evaluated.RESULTS RPA could achieved the optimal detection result for simplification of K.pneumoniae at 34 ℃ for 10 min.The LFD showed the best color development when Milipore HF 135s was used as the nitrocellulose membrane,phosphate buffered saline containing Tween-20(PBST)was used as the sample developing solution,and the concentrations of streptavidin and secondary antibody were 0.8 mg/ml and 0.1 mg/ml,respectively.The detection limit of the RPA-LFD was 5 CFU/ml for detection of K.pneumoniae,the relative standard deviation of the band color inten-sity was less than 5％in six parallel experiments,and there was no cross reactions with other bacterial strains.In addition,the sensitivity of the RPA-LFD in detection of K.pneumoniae was not affected by the serum compo-nents such as proteins and lipids.CONCLUSION The rapid detection method for K.pneumoniae that is established based RPA-LFD is characterized by the simple operation,high sensitivity and high specificity,and it does not need complicated equipment or strict technical requirement for operators and provides a new technique for early diagno-sis and epidemiological survey of the K.pneumoniae.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*