Navigating the immunometabolic heterogeneity of B cells in murine hepatocellular carcinoma at single cell resolution.

Induction of antitumor immunity is critical for the therapeutic efficacy of hepatocellular carcinoma (HCC) immunotherapy. The cellular metabolic state underpins the effector function of immune cells, yet our understanding of the phenotypic and metabolic heterogeneity of B cells within HCC microenvironment is poorly developed. Herein, we investigated the composition, distribution, phenotype, function and metabolic profiles of B-cell subsets in HCC and adjacent liver tissues from an orthotopic HCC mouse model using single-cell RNA sequencing (scRNA-seq). Our results identified six B-cell clusters, which can be classified into plasma cells and activated and exhausted B cells according to marker expression, functional and temporal distribution. Exhausted B cells exhibited low metabolic activities and impaired effector functions. Activated B and plasma cells showed higher metabolic activity than exhausted B cells, but there were clear differences in their metabolic profiles. In addition, we found that the effector function of exhausted B cells was further diminished in HCC tissues compared with adjacent liver tissues, but their metabolic activity was significantly enhanced. Collectively, we comprehensively characterized the metabolic profile and alterations in B-cell subsets in HCC, which contributes to the understanding of B-cell immunology in HCC and lays the foundation for exploring novel targets in HCC immunotherapy.

Serum vitamin D levels and acute kidney injury: a systemic review and meta-analysis.

Numerous researches have evaluated the prevalence and clinical outcome of vitamin D deficiency in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). But the quantitative vitamin D status in acute kidney injury (AKI) patients and its relationship with prognosis remains controversial. We conducted this systemic review and meta-analysis to assess the quantitative difference of vitamin D status, including serum 25(OH) D and 1,25(OH)2D levels, between AKI patients and non-AKI controls, and further explore whether vitamin D status can be clearly correlated with the mortality of AKI. Major databases, including PubMed, Web of Science and EBSCO, were searched until 1st September 2021. All published observational studies related to vitamin D and AKI According to predefined inclusion and exclusion criteria were extracted. Meta-analyses were performed using Review Manager 5.3.5. Four studies including five cohorts were included with a total of 413 patients. The serum 25(OH)D levels showed no statistically significant difference in AKI patients and non-AKI controls. On the other hand, the serum 1,25(OH)2D levels were significant lower in AKI patients than in non-AKI controls (MD = - 17.79, 95% CI = - 32.73 to - 2.85, P = 0.02). As for the relationship between serum vitamin D status and AKI patients' mortality, we were unable to give a consistent conclusion based on current limited and conflict study results. Our meta-analysis suggested that serum 1,25(OH)2D levels, rather than 25(OH)D, is significantly lower in AKI patients. The relationship between vitamin D status and clinical outcome of AKI remains controversial based on current evidence. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.

Genetic characterization and virulence determinants of multidrug-resistant NDM-1-producing Aeromonas caviae.

The emergence of carbapenemase significantly threatens public health. It is prevalent worldwide but rare in Aeromonas caviae. Unlike most bacterial species, A. caviae has two distinct flagella systems, which are closely related to biofilm formation. The ability to form biofilms on host tissues or inert surfaces constitutes an important cause of many persistent infections, which causes difficulties in clinical treatment. Here, we report on a multidrug-resistant (MDR) A. caviae carrying bla NDM-1 with a novel sequence type 1,416. The strong ability of biofilm formation of FAHZZU2447 was verified by a crystal violet assay. The resistome profile and location of the bla NDM-1 gene were determined by antimicrobial susceptibility testing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and Southern blot analysis. Moreover, the strain underwent whole-genome sequencing to identify its genomic characteristics. In addition, the bla NDM-1 gene was located on a ∼243 kb plasmid with genetic context IS1R-bla NDM-1-ble-trpF-dsbD-hp-sul1-qacE. Phylogenetic analysis indicated the transmission of A. caviae in China, Japan, and Thailand. Our study aimed to elucidate the genomic features of bla NDM-1-producing A. caviae, thereby clarifying the distribution of A. caviae worldwide and emphasizing the harmfulness of biofilm formation to the clinic. Further comprehensive surveillance of this species is needed to control further dissemination.

Correlation of Impaired NF-kB Activation in Sepsis-Induced Acute Lung Injury (ALI) in Diabetic Rats.

Background: The allergic lung inflammation is reduced in the diabetic rats which can be restored by treating it with insulin. As observed in multiple studies, the diabetic patients are more vulnerable to infections and their inflammatory reactions. There are confirmations on insulin and its effects control the inflammatory reactions. Objective: This study was performed to understand the correlation of impaired NF-kB activation in sepsis-induced acute lung injury (ALI) in diabetic rats. Material and Methods. Streptozotocin was used for induction of diabetes and sepsis was induced by colon ligation puncture surgery. Post 6 hours of CLP, the lungs in the groups were analyzed for cell infiltration using broncho-alveolar lavage. The lungs were removed for histopathological analysis at the end of study where the bronchioles, alveoli, and edema were analyzed and compared. Cell expressions quantified by the help of antibodies and inflammatory events were analyzed. Results: Diabetic rats developed mild acute lung injury due to the suppression of activation of NF-kB in alveolar macrophages. Conclusion: Even the diabetic rats were more susceptible to sepsis in comparison to the nondiabetic rats, but the NF-kB suppression has a major role to play in the faint symptoms of ALI.