Renal dysfunction (RD) often characterizes the worse course of patients with advanced heart failure (AHF). Many prognosis assessments are hindered by researcher biases, redundant predictors, and lack of clinical applicability. In this study, we enroll 1736 AHF/RD patients, including data from Henan Province Clinical Research Center for Cardiovascular Diseases (which encompasses 11 hospital subcenters), and Beth Israel Deaconess Medical Center. We developed an AI hybrid modeling framework, assembling 12 learners with different feature selection paradigms to expand modeling schemes. The optimized strategy is identified from 132 potential schemes to establish an explainable survival assessment system: AIHFLevel. The conditional inference survival tree determines a probability threshold for prognostic stratification. The evaluation confirmed the system’s robustness in discrimination, calibration, generalization, and clinical implications. AIHFLevel outperforms existing models, clinical features, and biomarkers. We also launch an open and user-friendly website www.hf-ai-survival.com, empowering healthcare professionals with enhanced tools for continuous risk monitoring and precise risk profiling.

The incidence of central nervous system (CNS) disease has persistently increased over the last several years. There is an urgent need for effective methods to improve the cure rates of CNS disease. However, the precise molecular basis underlying the development and progression of major CNS diseases remains elusive. A complete molecular map will contribute to research on CNS disease treatment strategies. Emerging technologies such as single-cell RNA sequencing (scRNA-seq) and Spatial Transcriptomics (ST) are potent tools for exploring the molecular complexity, cell heterogeneity, and functional specificity of CNS disease. scRNA-seq and ST can provide insights into the disease at cellular and spatial transcription levels. This review presents a survey of scRNA-seq and ST studies on CNS diseases, such as chronic neurodegenerative diseases, acute CNS injuries, and others. These studies offer novel perspectives in treating and diagnosing CNS diseases by discovering new cell types or subtypes associated with the disease, proposing new pathophysiological mechanisms, uncovering novel therapeutic targets, and identifying putative biomarkers. Graphical Abstract Implications of scRNA-seq and ST for CNS diseases. A comprehensive understanding of cellular information and spatial context using scRNA-seq and ST, helping to elucidate the biological functions, the intricate connection between crucial regulatory pathways, and cell communication after CNS diseases.

Cryptosporidium is a life-threating protozoan parasite belonging to the phylum Apicomplexa, which mainly causes gastroenteritis in a variety of vertebrate hosts. Currently, there is a re-emergence of Cryptosporidium infection; however, no fully effective drug or vaccine is available to treat Cryptosporidiosis. In the present study, to better understand the detailed interaction between the host and Cryptosporidium parvum, a large-scale label-free proteomics study was conducted to characterize the changes to the proteome induced by C. parvum infection. Among 4406 proteins identified, 121 proteins were identified as differentially abundant (> 1.5-fold cutoff, P < 0.05) in C. parvum infected HCT-8 cells compared with uninfected cells. Among them, 67 proteins were upregulated, and 54 proteins were downregulated at 36 h post infection. Analysis of the differentially abundant proteins revealed an interferon-centered immune response of the host cells against C. parvum infection and extensive inhibition of metabolism-related enzymes in the host cells caused by infection. Several proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. This systematic analysis of the proteomics of C. parvum-infected HCT-8 cells identified a wide range of functional proteins that participate in host anti-parasite immunity or act as potential targets during infection, providing new insights into the molecular mechanism of C. parvum infection.

Background: The main symptoms of schistosomiasis are granuloma and fibrosis, caused bySchistosomaeggs. Numerous types of cells and cytokines are involved in the progression ofSchistosomainfection. As a class of innate immune cells, γδ T cells play critical roles in the early immune response. However, their role in modulating granuloma and fibrosis remains to be clarified.Methods: Liver fibrosis in wild-type (WT) mice and T cell receptor (TCR) δ knockout (KO) mice infected withSchistosoma japonicumwas examinedviaMasson’s trichrome staining of collagen deposition and quantitative reverse transcriptase-PCR (RT-PCR) of fibrosis-related genes. Granuloma was detected by hematoxylin-eosin (H&E) staining and quantified. Flow cytometry was used for immune cell profiling and for detecting cytokine secretion. The abundance of the related cytokines was measured using quantitative RT-PCR.Results: The livers ofS. japonicum-infected mice had significantly increased proportions of interleukin (IL)-17A producing γδ T cells and secreted IL-17A. Compared with the WT mice, TCR δ deficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of γδ T cells in infected mice were associated with enhanced CD11b⁺Gr-1⁺cells, concurrent with increased expression of transforming growth factor (TGF)-β in the liver.Conclusions: In this mouse model ofSchistosomainfection, γδ T cells may promote liver fibrosis by recruiting CD11b⁺Gr-1⁺cells. These findings shed new light on the pathogenesis of liver pathology in murine schistosomiasis.

This study presents a case of Talaromyces marneffei combined with Enterococcus faecium bloodstream infection with gastrointestinal symptoms as the sole initial clinical manifestation.The patient is a resident of Shanghai and has no recent travel history to areas with a high risk of T. marneffei infection. He was admitted to the emergency room due to severe upper abdominal pain. Laboratory tests indicated elevated levels of white blood cells, rapid C-reactive protein, and procalcitonin, while the human immunodeficiency virus (HIV) test returned negative. An abdominal CT examination revealed gas and fluid accumulation in the abdominal cavity, raising suspicion for gastrointestinal perforation and peritonitis. Initially, he received symptomatic treatment for gastrointestinal perforation and abdominal infection, but his response to the treatment was poor.Through metagenomic next-generation sequencing (mNGS) and multiple blood cultures, a mixed infection of T. marneffei and E. faecium was identified in the patient’s blood. Combination treatment with vancomycin and amphotericin B was initiated to manage the symptoms. However, we discovered genome-wide exon CARD9 mutations in the patient, complicating the treatment process. Ultimately, the delayed diagnosis of T. marneffei resulted in the patient’s severe deterioration, rendering the anti-infective treatment ineffective, and leading to the patient’s death.This report underscores the challenges associated with diagnosing T. marneffei infections in non-AIDS patients and in non-endemic regions. The diagnosis of disseminated infections poses significant difficulties, particularly when mixed infections are present, complicating clinical treatment. This highlights the critical importance of standardized blood cultures for the early diagnosis of T. marneffei. Additionally, we must prioritize timely whole-genome testing to identify potential immune gene mutations.

Schistosoma japonicum eggs in the host liver form granuloma and liver fibrosis and then lead to portal hypertension and cirrhosis, seriously threatening human health. Natural killer (NK) cells can kill activated hepatic stellate cells (HSCs) against hepatic fibrosis. We used single-cell sequencing to screen hepatic NK cell subsets against schistosomiasis liver fibrosis. Hepatic NK cells were isolated from uninfected mice and mice infected for four and six weeks. The NK cells underwent single-cell sequencing. The markers’ expression in the NK subsets was detected through Reverse Transcription–Quantitative PCR (RT-qPCR). The proportion and granzyme B (Gzmb) expression of the total NK and Thy1⁺NK were detected. NK cells overexpressing Thy1 (Thy1-OE) were constructed, and functions were detected. The results revealed that the hepatic NK cells could be divided into mature, immature, regulatory-like, and memory-like NK cells and re-clustered into ten subsets. C3 (Cx3cr1⁺NK) and C4 (Thy1⁺NK) increased at week four post-infection, and other subsets decreased continuously. The successfully constructed Thy1-OE NK cells had significantly higher effector molecules and induced greater HSC apoptosis than the control NK cells. It revealed a pattern of hepatic NK cells in a mouse model of schistosomiasis. The Thy1⁺NK cells could be used as target cells against hepatic fibrosis.