Infections led by Acinetobacter baumannii strains are of great concern in healthcare environments due to the strong ability of the bacteria to spread through different apparatuses and develop drug resistance. Severe diseases can be caused by A. baumannii in critically ill patients, but its biological process and mechanism are not well understood. Secretion systems have recently been demonstrated to be involved in the pathogenic process, and five types of secretion systems out of the currently known six from Gram-negative bacteria have been found in A. baumannii. They can promote the fitness and pathogenesis of the bacteria by releasing a variety of effectors. Additionally, antibiotic resistance is found to be related to some types of secretion systems. In this review, we describe the genetic and structural compositions of the five secretion systems that exist in Acinetobacter. In addition, the function and molecular mechanism of each secretion system are summarized to explain how they enable these critical pathogens to overcome eukaryotic hosts and prokaryotic competitors to cause diseases.

Background: Early tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients.Methods: A total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated.Results: Early recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0 mm (HR: 1.601, P = 0.043) and surgical margin < 5.0 mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively.Conclusions: Elevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.

Background: Early recurrence of liver cancer is significantly associated with poor prognosis. Further dissection of the cellular heterogeneity in the tumor microenvironment (TME) of patients at high risk of early recurrence after liver cancer surgery is highly necessary. Methods: This study integrated clinical data, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data to reveal and verify a TME characteristic associated with high risk of early recurrence after liver cancer surgery. Results: Clinical analysis of 402 patients identified neutrophil-to-lymphocyte ratio ≥3, alpha-fetoprotein ≥400 ng/mL, and microvascular invasion as independent predictors of early recurrence. scRNA-seq of 28 hepatocellular carcinoma (HCC) samples revealed nine neutrophil subtypes, with SPP1⁺ neutrophils (enriched in TNFα/NF-κB, hypoxia, and TGF-β pathways) and exhausted CD8⁺ T cells (expressing PD-1 and CTLA-4) significantly infiltrating the TME of patients with early recurrence. These findings were corroborated in an independent validation cohort comprising scRNA-seq data from 17 HCC tissues and 7 matched peripheral blood samples. Spatial analysis demonstrated their co-localization at tumor margins, forming an immunosuppressive barrier. Ligand-receptor interaction analysis highlighted SPP1-CD44, TGFB1-TGFBR, and TNF-TNFRSF axes as key mediators of neutrophil–T cell crosstalk, inducing T cell dysfunction. Validation in The Cancer Genome Atlas–Liver Hepatocellular Carcinoma cohort comprising 365 patients confirmed that high infiltration of SPP1⁺ neutrophils and exhausted CD8⁺ T cells was significantly correlated with shorter recurrence-free ( P < 0.0001) and overall survival ( P < 0.0001). Conclusions: This study shows that the infiltration of SPP1⁺ neutrophils and exhausted CD8⁺ T cells is associated with a high risk of early recurrence in HCC. SPP1⁺ neutrophils may serve as key mediator of immune suppression through spatial interactions with exhausted CD8⁺ T cells, suggesting that they could be potential therapeutic targets to mitigate early recurrence in HCC.

Autoimmune liver diseases (AILDs) encompass autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The onset of these diseases is fundamentally influenced by genetic susceptibility. Although various extrahepatic factors are potentially linked to AILDs, the genetic underpinnings and mechanisms of these associations remain unclear. Utilizing large-scale genome-wide association study (GWAS) data, this study systematically investigated the relationships between extrahepatic autoimmune diseases (EHAIDs), immune cells, and various triggering factors with AILDs. Mendelian randomization (MR) was employed to assess the causal effects of these extrahepatic factors on AILDs, complemented by linkage disequilibrium score (LDSC) regression to uncover shared genetic architecture and causal effects underlying the associations between autoimmune diseases. We employed colocalization, enrichment analysis, and protein-protein interaction (PPI) network to identify the functions of shared loci. Additionally, we proposed that activated immune cells in the circulation may contribute to liver and biliary tract inflammation via migration, mediating the impact of extrahepatic factors on AILDs. This hypothesis was tested using two mediation analysis methods: two-step MR (TSMR) and multivariable MR (MVMR). Causal associations between multiple extrahepatic factors and AILDs were identified. Notably, CD27⁺ B cells were found to be a risk factor for PBC, while PSC progression was associated with CD28⁺ CD8⁺ T cells exhaustion and increased levels of CD28⁻ CD8⁺ T cells. Mediation analyses revealed 64 pathways via TSMR and 15 pathways via MVMR, indicating that the effects of extrahepatic factors on AILDs may be mediated by circulating immune cells. The shared genetic architecture also contributed to these associations. Analysis of shared loci and gene functions identified ATXN2 as being shared between PBC and 9 EHAIDs, while SH2B3 and PSMG1 were shared with 6 and 5 EHAIDs, respectively, in PSC. Our research compared three distinct AILDs, enhancing the understanding of their etiology and providing new evidence on risk factors, diagnostic markers, and potential therapeutic targets.