During our conveying the microbial structures of phycosphere microbiota (PM) derived from diverse marine harmful algal bloom (HAB) dinoflagellates, a new rod-sharped, white-colored cultivable bacterial strain, designated as LZ-15-2, was isolated from the PM of highly toxic Alexandrium catenella LZT09. Phylogenetic analysis of 16S rRNA gene sequence indicated that strain LZ-15-2 belonged to the genus Marivita within the family Rhodobacteraceae, and demonstrated the highest gene similarity of 99.2% to M. cryptomonadis CL-SK44^T, and less than 98.65% with other type strains of Marivita. Phylogenomic calculations on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the new isolate and M. cryptomonadis CL-SK44^T were 99.86% and 99.88%, respectively. Genomic comparison of strain LZ-15-2 with available genomes of Marivita species further verified its taxonomic position within the genus of Marivita. Moreover, comparative genomics analysis showed a proximal similarity of strain LZ-15-2 with M. cryptomonadis CL-SK44^T, and it also revealed an open pan-genome status based on constructed gene accumulation curves among Marivita members with 9,361 and 1,712 genes for the pan- and core-genome analysis, respectively. Based on combined polyphasic taxonomic characteristics, strain LZ-15-2 represents a new member of M. cryptomonadis, and proposed as a potential candidate for further exploration of the detailed mechanisms governing the dynamic cross-kingdom algae–bacteria interactions (ABI) between PM and their algal host LZT09.

The interplay between chemokine C-X-C motif ligand 12 (CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently, targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer (BCa), remains poorly elucidated. We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC). While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages (CD163⁺ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients. Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues, potentially influencing the treatment responses of affected individuals.

The development and metastasis of gastric cancer are complex processes involving the TME (Tumor microenvironment) and the interactions between various cell types. Here, we investigated the molecular mechanisms and biological processes underlying gastric cancer and its metastasis using single cell RNA-sequencing (scRNA-seq) with the aim of identifying new targets and approaches for clinical treatment. R version 4.4.1 and the SeuratV5 package were used to process 20 scRNA-seq samples sourced from the GEO database. Highly variable genes were selected for GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSAV (Gene set variation analysis) enrichment analyses. CytoTRACE, CellChat, and Monocle3 analyses were conducted to investigate cell communication and pseudotemporal dynamics in the PM (Peritoneal Metastasis) and GC (Gastric Cancer) groups. Additionally, the prognostic significance of key genes was assessed by integrating data from the TCGA clinical database. A total of 2,626,594 peritoneal metastasis cells and 17,894 gastric cancer cells were identified, revealing 13 distinct cell clusters. Gene enrichment analyses identified high expression in several pathways (P53, Wnt and JAK-STAT3) in TAMs and mast cells. Cell communication was more robust in the GC group than the PM group, with TAMs (Tumor-associated Macrophages) and mast cells showing elevated expression of the CCL5-CCR1 ligand-receptor signaling axis in both groups. Pseudotemporal analysis demonstrated the differentiation potential of TAMs into mast cells, with APOC1, C1QB, FCN1, FTL, S100A9, CD1C, CD1E and FCER1A identified as the top eight genes driving this process. High expression levels of these genes, along with CCL5 and CCR1, were associated with poor long-term survival in cancer patients. scRNA-seq identified the intricate tumor immune microenvironment, highlighting the pivotal roles of TAMs and mast cells in gastric cancer peritoneal metastasis. The CCL5-CCR1 pathway emerged as a potential immune checkpoint, offering novel insights for future immunotherapeutic and targeted therapeutic strategies in the treatment of gastric cancer peritoneal metastasis.

Importance: The protective efficacy of COVID-19 vaccinations has declined over time such that booster doses are required. Objective: To evaluate the efficacy and adverse events of booster doses of two inactivated COVID-19 vaccines. Design: This is a double-blind, randomized, placebo-controlled phase 3 trial aiming to evaluate the protective efficacy, safety, and immunogenicity of inactivated SARS-CoV-2 vaccine (Vero cells) after inoculation with booster doses of inactivated COVID-19 vaccine. Setting: Healthy volunteers were recruited in an earlier phase 3 trial of two doses of inactivated vaccine. The participants in Abu Dhabi maintained the blind state of the trial and received a booster dose of vaccine or placebo at least six months after the primary immunization. Participants: Adults aged 18 and older with no history of SARS-CoV, SARS-CoV-2, or Middle East respiratory syndrome infection (via onsite inquiry) were screened for eligibility. Interventions: A total of 9370 volunteers were screened and randomly allocated, of which 61 voluntarily withdrew from the screening stage without booster inoculation; 9309 received the booster vaccination, with 3083 in the WIV04 group, 3150 in the HB02 group, and 3076 in the alum-only group. Further, 5μg and 4μg of inactivated SARS-CoV-2 virion was adsorbed into aluminum hydroxide in a 0.5 mL aqueous suspension for WIV04 and HB02 vaccines. Main Outcomes and Measures: The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 from 14 days after the booster vaccine in the per-protocol population. A safety analysis was performed in the intention-to-treat population. Results: Symptomatic COVID-19 was identified in 36 participants in the WIV04 group (9.9 [95% CI, 7.2–13.8] per 1000 person-years), 28 in the HB02 group (7.6 [95% CI, 5.2–11.0] per 1000 person-years), and 193 in the alum-only group (55.2 [95% CI, 47.9–63.5] per 1000 person-years), resulting in a vaccine efficacy of 82.0% (95% CI, 74.2–87.8%) for WIV04 and 86.3% (95% CI, 79.6–91.1%) for HB02. One severe case of COVID-19 occurred in the alum-only group, and none occurred in the vaccine groups. Adverse reactions within seven days after vaccination occurred in 29.4% to 34.3% of participants in the three groups. Serious adverse events were rare and not related to vaccines (WIV04: 17 [0.5%]; HB02: 11 [0.4%]; alum only: 40 [1.3%]). Conclusions and Relevance: This study evaluated the safety of the booster dose, which was well tolerated by participants. Booster doses given over six months after the completion of primary immunization can help to provide more-effective protection against COVID-19 in healthy people 18 years of age or older. At the same time, the anti-SARS-CoV-2 antibodies produced by the two groups of experimental vaccines exhibited extensive cross-neutralization against representative SARS-CoV-2 variants. Trial Registration: This study is registered on ClinicalTrials.gov (NCT04510207).

To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.