Introduction
The objective of this study is to thoroughly analyze the detailed genomic characteristics of clinical strain 211703 of
Aeromonas caviae
, which co-carrying
bla
RSA-1
and
bla
NDM-1
genes. ...211703 was isolated from the patient’s cerebrospinal fluid drainage sample in a Chinese tertiary hospital.
Methods
Carbapenemase NDM was detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. The whole genome sequence of 211703 was analyzed using phylogenetics, genomic comparison, and extensive dissection.
Results
This study revealed that 211703 only contained a single 4.78 Mb chromosome (61.8% GC content), and no plasmids were discovered in 211703. 15 different types of resistant genes were detected in the genome of 211703, including
bla
RSA-1
harbored on integrative and mobilizable element (IME) Tn
7413a
, and
bla
NDM-1
harbored on integrative and conjugative element (ICE). The ICE and IME were all carried on the chromosome of 211703 (c211703). Detailed comparison of related IMEs/ICEs showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed that
bla
RSA-1
was carried by the gene cassette of a novel integron In2148 on Tn
7413a
, and
bla
NDM-1
was captured by an insertion sequence IS
CR14
-like on the ICE of 211703. We speculated that mobile genetic elements (MGEs) such as ICE and IME facilitated the spread of resistance genes such as
bla
RSA-1
and
bla
NDM-1
.
Discussion
In conclusion, this study provides an overall understanding of the genomic characterization of clinically isolated
A. caviae
211703, and an in-depth discussion of multiple acquisition methods of drug resistance genes in
Aeromonas
. To the best of our knowledge, this is the first report of
A. caviae
carrying
bla
RSA-1
even both
bla
RSA-1
and
bla
NDM-1
, and this is the first bacterium carrying
bla
RSA-1
isolated from the clinical setting.
How introns enhance gene expression Shaul, Orit
The international journal of biochemistry & cell biology,
October 2017, 2017-10-00, 20171001, Volume:
91, Issue:
Pt B
Journal Article
Peer reviewed
In many eukaryotes, including mammals, plants, yeast, and insects, introns can increase gene expression without functioning as a binding site for transcription factors. This phenomenon was termed ...‘intron-mediated enhancement’. Introns can increase transcript levels by affecting the rate of transcription, nuclear export, and transcript stability. Moreover, introns can also increase the efficiency of mRNA translation. This review discusses the current knowledge about these processes. The role of splicing in IME and the significance of intron position relative to the sites of transcription and translation initiation are elaborated. Particular emphasis is placed on the question why different introns, present at the same location of the same genes and spliced at a similar high efficiency, can have very different impacts on expression − from almost no effect to considerable stimulation. This situation can be at least partly accounted for by the identification of splicing-unrelated intronic elements with a special ability to enhance mRNA accumulation or translational efficiency. The many factors that could lead to the large variation observed between the impact of introns in different genes and experimental systems are highlighted. It is suggested that there is no sole, definite answer to the question “how do introns enhance gene expression”. Rather, each intron-gene combination might undergo its own unique mixture of processes that lead to the perceptible outcome.
The objective of this investigation was to analyse the correlation between the neutrophil-to-lymphocyte ratio (NLR) status in the immune microenvironment (IME) and the prognostic outcomes of patients ...who have undergone radical surgery for colorectal cancer (CRC).
In light of the continued prevalence of CRC in China, this study utilised Kaplan–Meier and Cox regression analyses to assess the prognostic relevance of NLR status in IME among patients with CRC. Furthermore, cellular experiments, such as cell scratching, were conducted to elucidate the underlying mechanisms of NLR's impact on CRC.
The NLR status in IME has been found to have a significant impact on the prognosis of patients with CRC. Patients who exhibit elevated intratumoural and extratumoural NLR are associated with a poor prognosis. Experimental evidence indicates that tumour-associated neutrophil (TAN) augments the migratory, invasive, and proliferative potential of HT-29, HCT-116 and LOVO colorectal cancer cells, while concurrently reducing their sensitivity to oxaliplatin. Conversely, lymphocytes have demonstrated cytotoxic effects on HT-29 cells.
The NLR status in IME may serve as a prognostic biomarker for resectable CRC.
Traditional wastewater treatment methods are often insufficient in the case of mature landfill leachate. Therefore novel methods are in demand. Recently, internal microelectrolysis (IME) has been ...recognized as an effective method besides AOPs for refractory wastewaters treatment. This study investigated the efficiency of a novel combined three-step process (IME-O3/OH−/H2O2) applied to mature landfill leachate treatment. Waste iron chips and granulated activated carbon (GAC) from nut shells were used in the process. Ozone was applied in doses from 0.28 to 1.4 g/dm3, and the mass ratios of COD/H2O2 were as follows: 1/0, 1/0.5, 1/1 1/1.5, and 1/2. Results showed that the PC is a reasonable pretreatment process before IME. However, COD and TOC removal was up to 22.4% and 37.9%, respectively. It required no additional reagents (before IME acidification is needed). The best total COD removal in the IME process was for Fe/GAC ratio 20/80 g/g in 1 dm3 (76.7%). Studies on the sorption process on GAC showed a significant share in the IME process - 11.2–62.6% of total COD removal. That was an important observation since most other authors ignored the fact of sorption. For optimal parameters of the O3/OH−/H2O2, total COD removal was 95.4%. The values of TOC, absorbance UV254, and color were highly reduced by 91.2%, 94.7%, and 98.2%, respectively. Additionally, biodegradability has been significantly improved up to 0.36.
Display omitted
•Improvement of IME process by preliminary coagulation as the first step•Using microelectrodes from waste Fe-chips and GAC from nut shells•COD removal by 95.4% and TOC by 91.2% after a three-step process•High color removal (98.2%) and reduction of the UV254 absorbance by 94.7%•Improvement of biodegradability (BOD5/COD ratio up to 0.36)
Periodontitis is one of the most common dental diseases. Compared with healthy periodontal tissues, the immune microenvironment plays the key role in periodontitis by allowing the invasion of ...pathogens. It is possible that modulating the immune microenvironment can supplement traditional treatments and may even promote periodontal regeneration by using stem cells, bacteria, etc. New anti-inflammatory therapies can enhance the generation of a viable local immune microenvironment and promote cell homing and tissue formation, thereby achieving higher levels of immune regulation and tissue repair. We screened recent studies to summarize the advances of the immunomodulatory treatments for periodontitis in the aspects of drug therapy, microbial therapy, stem cell therapy, gene therapy and other therapies. In addition, we included the changes of immune cells and cytokines in the immune microenvironment of periodontitis in the section of drug therapy so as to make it clearer how the treatments took effects accordingly. In the future, more research needs to be done to improve immunotherapy methods and understand the risks and long-term efficacy of these methods in periodontitis.
The Island Mass Effect (IME) around the Maldives is responsible for intense blooms with distinct seasonal patterns. These blooms sustain the fishing industry of the archipelagic nation, a vital ...source of income that occupies about 30% of the population. Through high resolution ocean simulations, we explore the physical processes responsible for the increased productivity and its observed variability, and their sensitivity to changes in land distribution. Year-round the frictional break of the currents in the presence of shallow bathymetry produces a strong vertical shear in the flow that favors vertical mixing, independently of the currents direction. The impact of this mixing is visible at the ocean surface during March and April, when the mixed-layer is shallow and the ocean currents are generally weak. A different mechanism than observed in spring modulates the IME during the monsoon seasons, in both winter and summer, when the zonal currents forced by the strong winds cross the archipelago: the flow accelerates while squeezing between the atolls, giving rise to intense wakes, and strong upwelling originates in the lees in response to the kilometer-scale flow divergence. This upwelling creates an asymmetric cooling signal in the lee of the islands and obfuscates the effects of the enhanced vertical mixing. The land reclamation efforts being planned on some of the islands may undercut the upwelling that drives the blooms during the monsoon seasons.
Background
Breast cancer is the most common cancer worldwide. Hypoxia and lactate metabolism are hallmarks of cancer. This study aimed to construct a novel hypoxia- and lactate metabolism-related ...gene signature to predict the survival, immune microenvironment, and treatment response of breast cancer patients.
Methods
RNA-seq and clinical data of breast cancer from The Cancer Genome Atlas database and Gene Expression Omnibus were downloaded. Hypoxia- and lactate metabolism-related genes were collected from publicly available data sources. The differentially expressed genes were identified using the “edgeR” R package. Univariate Cox regression, random survival forest (RSF), and stepwise multivariate Cox regression analyses were performed to construct the hypoxia-lactate metabolism-related prognostic model (HLMRPM). Further analyses, including functional enrichment, ESTIMATE, CIBERSORTx, Immune Cell Abundance Identifier (ImmuCellAI), TIDE, immunophenoscore (IPS), pRRophetic, and CellMiner, were performed to analyze immune status and treatment responses.
Results
We identified 181 differentially expressed hypoxia-lactate metabolism-related genes (HLMRGs), 24 of which were valuable prognostic genes. Using RSF and stepwise multivariate Cox regression analysis, five HLMRGs were included to establish the HLMRPM. According to the medium-risk score, patients were divided into high- and low-risk groups. Patients in the high-risk group had a worse prognosis than those in the low-risk group (
P
< 0.05). A nomogram was further built to predict overall survival (OS). Functional enrichment analyses showed that the low-risk group was enriched with immune-related pathways, such as antigen processing and presentation and cytokine-cytokine receptor interaction, whereas the high-risk group was enriched in mTOR and Wnt signaling pathways. CIBERSORTx and ImmuCellAI showed that the low-risk group had abundant anti-tumor immune cells, whereas in the high-risk group, immunosuppressive cells were dominant. Independent immunotherapy datasets (IMvigor210 and GSE78220), TIDE, IPS and pRRophetic analyses revealed that the low-risk group responded better to common immunotherapy and chemotherapy drugs.
Conclusions
We constructed a novel prognostic signature combining lactate metabolism and hypoxia to predict OS, immune status, and treatment response of patients with breast cancer, providing a viewpoint for individualized treatment.
•We first identified two novel m6A subtypes in pituitary adenomas (PAs) based on the m6A regulator gene set. These subtypes exhibit distinct characteristics in tumor immune microenvironment, ...suggesting diverse responses to immunotherapy.•YTHDF2 showed a correlation with elevated levels of M2 macrophages and PD-L1 expression, making it a promising biomarker for immunotherapy and a potential molecular target in PAs.•A clinically accessible polygenic nomogram model was constructed to predict the m6A subtype classification in PAs. This nomogram demonstrated excellent predictive performance and can aid in clinical decision-making.
N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment (IME) have an essential role in tumor development. However, their relationships in pituitary adenomas (PAs) remains unclear.
PA datasets from the Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EMBL-EBI) were used. We utilized hierarchical clustering algorithms based on the m6A regulator gene set to identify m6A subtypes. ESTIMATE and CIBERSORT algorithms were applied to explore the compositions of stromal and immune cells. A nomogram model was constructed for the prediction of m6A subtypes in PAs. Immunohistochemistry and multiplex immunofluorescence staining were used to analyze the expression level of m6A regulator YTHDF2 in relation to M2 macrophages and immune checkpoints in PAs.
We concluded the IME landscape of m6A subtype classification and characterized two emerging m6A subtypes. Different IME between these two m6A subtypes were identified. Simultaneously, a polygenic nomogram model was constructed for predicting m6A subtype classification, with excellent predictive performance (training set, AUC = 0.984; validation set, AUC = 0.986). YTHDF2 was highly expressed in PAs and accompanied by upregulated M2 macrophages and expression of PD-L1.
We proposed two novel m6A subtypes in PAs for the first time and constructed a reliable and clinically accessible nomogram model for them. Meanwhile, YTHDF2 was first identified as a promising biomarker for immunotherapy and potential molecular target in PAs.
, an emerging zoonotic pathogen, is important reservoirs of antibiotic resistance genes that play critical roles in the horizontal transfer of corresponding resistances. In the present study, 656 ...antibiotic resistance (AR) genes were detected in 154 of 155 genomes of
strains isolated from the nasopharynx of slaughtered pigs and the lungs of diseased pigs in China. The AR genes were clustered into 11 categories, consisting of tetracycline, macrolides, lincosamide, streptogramin, aminoglycoside, trimethoprim, amphenicols, nucleoside, quinupristin/dalfopristin, glycopeptide, and oxazolidinones resistance genes. In order to investigate the transmission patterns of the AR genes, AR genes-associated the mobile genetic elements (MGEs) were extracted and investigated. Twenty ICEs, one defective ICE, one tandem ICE, and ten prophages were found, which mainly carried tetracycline, macrolides/lincosamides/streptogramin (MLS), and aminoglycosides resistance genes. Three types of DNA cargo with AR genes were integrated into specific sites of ICEs: integrative mobilizable elements (IMEs),
-IMEs (CIMEs), and transposon Tn
. Obvious differences in AR gene categories were found among the three cargo types. IMEs mainly harbored tetracycline and MLS resistance genes. CIMEs mainly carried aminoglycoside resistance genes, while transposon Tn
carried only the
(M) gene. Nearly all AR genes in ICEs were carried by IMEs and CIMEs. IMEs were prevalent and were also detected in additional 29
genomes. The horizontal transfer of IMEs and CIMEs may play critical role in ICE evolution and AR gene transmission in the
population. Our findings provide novel insights into the transmission patterns of AR genes and the evolutionary mechanisms of ICEs in
.
Background
Tumor immunological heterogeneity potentially influences the prognostic disparities among patients with clear cell renal cell carcinoma (ccRCC); however, there is a lack of macroscopic ...imaging tools that can be used to predict immune-related gene expression in ccRCC.
Methods
A novel non-invasive radiogenomics biomarker was constructed for immune-related gene expression in ccRCC. First, 520 ccRCC transcriptomic datasets from The Cancer Genome Atlas (TCGA) were analyzed using a non-negative matrix decomposition (NMF) clustering to identify immune-related molecular subtypes. Immune-related prognostic genes were analyzed through Cox regression and Gene Set Enrichment Analysis (GSEA). We then built a risk model based on an immune-related gene subset to predict prognosis in patients with ccRCC. CT images corresponding to the ccRCC patients in The Cancer Imaging Archive (TCIA) database were used to extract radiomic features. To stratify immune-related gene expression levels, extracted radiogenomics features were identified according to standard consecutive steps. A nomogram was built to combine radiogenomics and clinicopathological information through multivariate logistic regression to further enhance the radiogenomics model. Mann–Whitney U test and ROC curves were used to assess the effectiveness of the radiogenomics marker.
Results
NMF methods successfully clustered patients into diverse subtypes according to gene expression levels in the tumor microenvironment (TME). The relative abundance of 10 immune cell populations in each tissue was also analyzed. The immune-related genomic signature (consisting of eight genes) of the tumor was shown to be significantly associated with survival in patients with ccRCC in TCGA database. The immune-related genomic signature was delineated by grouping the signature expression as either low- or high-risk. Using TCIA database, we constructed a radiogenomics biomarker consisting of 11 radiomic features that were optimal predictors of immune-related gene signature expression levels, which demonstrated AUC (area under the ROC curve) values of 0.76 and 0.72 in the training and validation groups, respectively. The nomogram built by combining radiomics and clinical pathological information could further improve the predictive efficacy of the radiogenomics model (AUC = 0.81, 074).
Conclusions
The novel prognostic radiogenomics biomarker achieved excellent correlation with the immune-related gene expression status of patients with ccRCC and could successfully stratify the survival status of patients in TCGA database. It is anticipated that this work will assist in selecting precise clinical treatment strategies. This study may also lead to precise theranostics for patients with ccRCC in the future.
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