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Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment. [ABSTRACT FROM AUTHOR]

A Gram-negative, facultatively anaerobic, short rod-shaped bacterium, designated as strain HZ0627T, was isolated from the appendiceal pus of a patient with appendicitis in Yongzhou, Hunan, China. This strain was subjected to comprehensive phenotypic, phylogenetic, and genomic analyses using polyphasic taxonomic methods. Phylogenetic analysis of the 16S rRNA gene sequence revealed that this strain belonged to the genus Proteus and the family Morganellaceae, whereas that based on the rpoB gene sequence and phylogenomic analysis demonstrated that this strain was distinctly separated from other type strains of Proteus species. Moreover, whole-genome-based analyses, including in silico DNA–DNA hybridization (isDDH) and average nucleotide identity (ANI), revealed that strain HZ0627T had much lower isDDH rates (24.5–55.6%) and ANI (82.04–93.90%) than those of the thresholds (i.e., 70% and 95%, respectively) for species delineation, when compared to the type strains of other Proteus species. The cellular fatty acid profile of strain HZ0627T was dominated by C16:0 (34.5%), cyclo C17:0 (25.8%), C14:0 (12.6%), C16:1 iso I/14:0 3-OH (7.7%), C18:1ω7c/18:1ω6c (6.5%), and C16:1ω7c/16:1ω6c (4.9%), which clearly differentiated it from the documented type strains of Proteus species. In addition, several specific physiological traits, including optimal growth temperature, tolerance to sodium chloride, and carbon source utilization, differed from those of other Proteus species. Therefore, we propose the name Proteus appendicitidis sp. nov. for strain HZ0627T (= CCTCC AB 2022380T = KCTC 92986T), which represents the type strain of this novel Proteus species. [ABSTRACT FROM AUTHOR]

Public concerns are increasing regarding the prevalence and transmission of antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs), especially ARG persistence and dissemination in activated sludge (AS). However, the temporal dynamics of ARGs in the AS of WWTPs over a long period of time and their transfer potential after the treatment process upgrade (e.g., total nitrogen reduction from 20 to 15 mg/L in effluent) remain poorly explored. Here, metagenomic sequencing was performed to quantify the ARGs in AS samples from two WWTPs with different treatment processes over a 2-year period. A total of 368 and 426 ARG subtypes affiliated with 20 ARG types were identified separately in the two WWTPs and the similar core ARGs were shared by all 54 samples. There were significant differences in ARG composition in different treatment processes, yet the abundance and diversity of ARGs in the AS samples demonstrated no distinct seasonal patterns. Notably, after the treatment process upgrade, the relative abundance of sulfonamide, beta-lactam, and aminoglycoside resistance genes was reduced by more than 10%, and the transfer potential of ARGs in bacterial pathogens decreased greatly, which suggested that an upgrade could limit the prevalence and transmission of ARGs. Variation partitioning analysis showed that metal resistance genes rather than bacterial community represented the significantly influential factor in shaping ARGs, and some key genera correlated with ARGs were identified through network analysis. These results will deepen our understanding of the dynamic changes in ARG profiles in AS systems and guide wastewater treatment plant upgrades. Key points: • The potential transfer of ARGs decreased after the treatment process upgrade • Metal resistance genes were the most influential factor in shaping ARG composition • Co-occurrence networks displayed potential hosts of beta-lactam resistance genes [ABSTRACT FROM AUTHOR]

As a possible human carcinogen, bromate is easily formed in drinking water and wastewater treatments using advanced oxidation technology. Microbial reduction is a promising method to remove bromate, but little is known about aerobic bromate reduction as well as the molecular mechanism of tolerance and reduction to bromate in bacteria. Herein, bromate reduction by isolate under aerobic conditions was reported for the first time. Shewanella decolorationis Ni1-3, isolated from an activated sludge recently, was identified to reduce bromate to bromide under both aerobic and anaerobic conditions. RNA-Seq together with differential gene expression analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify that bromate triggered the expression of genes for oxidative stress protection (e.g., ohr, msrQ, dsbC, gpo, gorA, and gst), DNA damage repair (e.g., dprA, parA, and recJ), and sulfur metabolism (e.g., cysH, cysK, and cysP). However, the genes for lactate utilization (e.g., lldF and dld), nitrate reduction (e.g., napA and narG), and dissimilatory metal reduction (e.g., mtrC and omcA) were down-regulated in the presence of bromate. The results contribute to revealing the molecular mechanism of resistance and reduction in S. decolorationis Ni1-3 to bromate under aerobic conditions and clarifying the biogeochemical cycle of bromine. Key points: • Aerobic bromate reduction by pure culture was observed for the first time • Strain Ni1-3 effectively reduced bromate under both aerobic and anaerobic conditions • ROS and SOS response genes were strongly induced in the presence of bromate [ABSTRACT FROM AUTHOR]

Bacterial communities in the activated sludge (AS) determine the wastewater treatment performance in the municipal wastewater treatment plants (WWTPs). Aiming at identifying the affecting factors and the variation patterns of the bacterial assemblages in AS, a 2-year time-series AS samples were collected from two separated WWTPs and metagenomic sequencing was conducted. Obvious seasonal shift and succession of the bacterial community were observed in both WWTPs on the genus and species levels, especially for the persistent taxa, implying that temperature was a decisive factor for maintaining bacterial assemblage patterns in long-term period. Taxa abundance distribution (TAD) concerning occurrence frequency and average abundance were found fitting for exponential formulations, and the approximately equal total abundance of persistent taxa suggested that stable and high abundance (~ 90%) of core functional bacterial groups would help to maintain wastewater treatment performance. Drastic changes of environmental factors were found causing temporally significant bacterial structure variation, while the innate correlations between bacterial species could recover the community gradually and maintain relative stability of the AS system. Delayed correlations between environmental factors and abundant (persistent or intermittent) bacterial species were observed widely, while synchronous biotic interactions were identified more frequently. Besides, bacterial species with similar functions were prone to cluster together and shared the same seasonal variation pattern, implicating that the cooperation of functional correlated taxa played the most dominant role in shaping the bacterial assemblages. Furthermore, rare bacterial groups were to be explored for removing emerging pollutants with lower concentrations. The results of this study would assist dealing with operational defect and optimize the treatment system in WWTPs. [ABSTRACT FROM AUTHOR]