Berberine alleviates contrast-induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway.

Contrast-induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine-based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK-2 cells. BBR reduced ioversol-induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p-Akt and p-Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol-induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine-based contrast agents.

Cytokine, chemokine alterations and immune cell infiltration in Radiation-induced lung injury: Implications for prevention and management.

Radiation therapy is one of the primary treatments for thoracic malignancies, with radiation-induced lung injury (RILI) emerging as its most prevalent complication. RILI encompasses early-stage radiation pneumonitis (RP) and the subsequent development of radiation pulmonary fibrosis (RPF). During radiation treatment, not only are tumor cells targeted, but normal tissue cells, including alveolar epithelial cells and vascular endothelial cells, also sustain damage. Within the lungs, ionizing radiation boosts the intracellular levels of reactive oxygen species across various cell types. This elevation precipitates the release of cytokines and chemokines, coupled with the infiltration of inflammatory cells, culminating in the onset of RP. This pulmonary inflammatory response can persist, spanning a duration from several months to years, ultimately progressing to RPF. This review aims to explore the alterations in cytokine and chemokine release and the influx of immune cells post-ionizing radiation exposure in the lungs, offering insights for the prevention and management of RILI.

Berberine ameliorates contrast-induced acute kidney injury by regulating HDAC4-FoxO3a axis-induced autophagy: In vivo and in vitro.

In hospitals, contrast-induced acute kidney injury (CI-AKI) is a major cause of renal failure. This study evaluates berberine's (BBR) renal protection and its potential HDAC4 mechanism. CI-AKI in rats was induced with 10 mL kg-1 ioversol. Rats were divided into five groups: Ctrl, BBR, CI-AKI, CI-AKI + BBR, and CI-AKI + Tasq. The renal function of CI-AKI rats was determined by measuring serum creatinine and blood urea nitrogen. Histopathological changes and apoptosis of renal tubular epithelial cells were observed by HE and terminal deoxynucleotidyl transferase (TdTase)-mediated dUTP-biotin nick end labeling (TUNEL) staining. Transmission electron microscopy was used to observe autophagic structures. In vitro, a CI-AKI cell model was created with ioversol-treated HK-2 cells. Treatments included BBR, Rapa, HCQ, and Tasq. Analyses focused on proteins and genes associated with kidney injury, apoptosis, autophagy, and the HDAC4-FoxO3a axis. BBR showed significant protective effects against CI-AKI both in vivo and in vitro. It inhibited apoptosis by increasing Bcl-2 protein levels and decreasing Bax levels. BBR also activated autophagy, as indicated by changes in autophagy-related proteins and autophagic flux. The study further revealed that the contrast agent ioversol increased the expression of HDAC4, which led to elevated levels of phosphorylated FoxO3a (p-FoxO3a) and acetylated FoxO3a (Ac-FoxO3a). However, BBR inhibited HDAC4 expression, resulting in decreased levels of p-FoxO3a and Ac-FoxO3a. This activation of autophagy-related genes, regulated by the transcription factor FoxO3a, played a role in BBR's protective effects. BBR, a traditional Chinese medicine, shows promise against CI-AKI. It may counteract CI-AKI by modulating HDAC4 and FoxO3a, enhancing autophagy, and limiting apoptosis.

Exploring the impact of cognitive impairments on treatment compliance and quality of life in patients with Continuous Ambulatory Peritoneal Dialysis (CAPD).

The aim of this study is to investigate the impact of cognitive impairments on treatment compliance and quality of life in patients with Continuous Ambulatory Peritoneal Dialysis (CAPD). A cross-sectional study was conducted among patients with CAPD at the Department of Nephrology, Lianshui People's Hospital from October 2021 to May 2022. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and the End-Stage Renal Disease Adherence Questionnaire was used to evaluate treatment compliance. Quality of life was assessed using the SF-36 questionnaire. Scores from all the questionnaires and demographic data were recorded. A total of 98 patients were enrolled, and the prevalence of cognitive impairment among CAPD patients was 69.39% (MoCA score < 26). Patients were divided into 2 groups: one group with normal cognitive function (MoCA score ≥ 26) and the other with cognitive impairments. There were statistically significant differences in age, dialysis age, education, urea clearance index, history of high blood pressure, and diabetes between the 2 groups (all P < .05). Patients with cognitive impairments had lower compliance levels in terms of diet fluid restriction, medication therapeutic regimens, and dialysis regimen (all P < .05). Patients with cognitive impairments also had lower quality of life scores in the dimensions of physical function, general health, social function, emotional function, and mental health (all P < .05). Cognitive impairment appears to be common among CAPD patients and may adversely affect both their treatment adherence and overall quality of life. A more comprehensive understanding of the underlying mechanisms necessitates further study.

Bacterial cell sensing and signaling pathway for external polycyclic aromatic hydrocarbons (PAHs).

The mechanism by which a bacterial cell senses external nutrients remains largely unknown. In this study, we identified a bacterial cell sensing system for polycyclic aromatic hydrocarbons (PAHs) in a common marine PAH-using bacterium, Cycloclasticus. It consists of an outer membrane receptor (PahS) and a periplasmic protein (PahP) in combination with a two-component sensing system (TCS) that ensures a rapid response to PAH occurrence by directly controlling serial reactions including chemotactic sensing and movement, PAH uptake and intracellular PAH metabolism. PahS protrudes from the cell and acts as a PAH sensor, transducing the PAH signal across the outer membrane to its periplasmic partner PahP, which in turn transduces the PAH signal across the periplasm to a specialized TCS. This sensing system plays a critical role in sensing and promoting the metabolism of PAHs, which can be scavenged by various hydrocarbon-degrading bacteria.

Activation of Nrf2/ARE pathway by Anisodamine (654-2) for Inhibition of cellular aging and alleviation of Radiation-Induced lung injury.

BACKGROUND: Radiation-induced lung injury (RILI) is a common side effect of thoracic tumor radiotherapy, including early-stage radiation-induced lung injury (RP) and late-stage radiation-induced pulmonary fibrosis (RIPF). Currently, it is urgently needed to clarify the pathogenesis of RILI and find safe and effective RILI treatment methods. Irradiation causes DNA damage and oxidative stress in tissues and cells, induces cellular senescence, and promotes the occurrence and development of RILI. In recent years, Anisodamine (654-2) has shown potential therapeutic value in acute lung injury, acute kidney injury, chlamydial pneumonia, and COVID-19. However, there is currently no research on the mechanism of 654-2-mediated cellular senescence and its preventive and therapeutic effects on RILI. PURPOSE: This study aimed to investigate the protective effect and mechanism of 654-2 on X-ray-induced RILI. METHODS: In vivo experiments involved a mouse RILI model with 18 Gy X-ray irradiation. Mice were divided into control, model, medication (control + 654-2), and treatment (model + 654-2) groups. And mice in medication and treatment groups were intraperitoneal injection of 5 mg/kg 654-2 every other day until being sacrificed at week 6. In vitro experiments used MLE-12 cells irradiated with 16 Gy and divided into control, model, and model + 654-2（2 µM and 10 µM） groups. Various assays were performed to evaluate lung tissue morphology, fibrosis, apoptosis, cytokine expression, cellular senescence, protein expression, and antioxidant capacity. RESULTS: 654-2 mitigated pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis in RILI mice and MLE-12 cells. It restored epithelial cell proliferation ability and enhanced antioxidant capacity. Additionally, 654-2 activated the Nrf2/ARE pathway, increased Nrf2 phosphorylation, and upregulated antioxidant gene expression. Inhibition of Nrf2 reversed the effects of 654-2 on ROS production, antioxidant capacity, and cell senescence. CONCLUSION: 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI.

The clinical predictive value and regulation mechanism of microRNA-188-5p in contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN), has become the third leading cause of iatrogenic AKI. Serum creatinine (Scr) is currently used in CIN clinical diagnosis. Patients with increased Scr have developed severe kidney injury, so there is an urgent need to find a bio-marker for CIN early diagnosis. To investigate the changes in circulating microRNA-188-5p (miR-188-5p) after coronary angiography and its predictive value for the CIN occurrence, miR-188-5p expression in CIN rats from the GEO database and CIN patients and control patients from Lianshui People's Hospital was analyzed. The results showed that miR-188-5p expression in plasma and renal was higher in CIN group than in control group. Further, a total of 36 CIN patients and 108 non-CIN patients were included. There were significant differences in age, hypertension, diabetes, and contrast agent dosage. After 12 h of contrast agent application, circulating miR-188-5p expression in CIN group was higher than control group. Univariate and multivariate logistic regression analysis showed that age, hypertension, diabetes, contrast media dosage and postoperative miR-188-5p expression were closely related to CIN occurrence. For in vitro experiments, intracellular miR-188-5p expression was decreased with ioversol treatment, while miR-188-5p expression in supernatant was increased. To explore the potential mechanism of miR-188-5p in CIN, HK-2 cells were treated with NC mimic, ioversol, or miR-188-5p mimic. The results showed that the application of miR-188-5p mimic reduced apoptosis, reactive oxygen species and MDA, enhanced SOD and GSH contents. Further, it was confirmed that mRNA and protein levels of PTEN were up-regulated in ioversol-treated HK-2 cells, and down-regulated after miR-188-5p administration. Dual-luciferase reporter gene assay confirmed that PTEN was direct target gene of miR-188-5p. Above results suggest that circulating miR-188-5p has the potential to serve as a predictor of CIN.

Comparison of prognostic value between CAD-RADS 1.0 and CAD-RADS 2.0 evaluated by convolutional neural networks based CCTA.

Objectives: The aim of the present study was to investigate the prognostic value of the novel coronary artery disease reporting and data system (CAD-RADS) 2.0 compared with CAD-RADS 1.0 in patients with suspectedcoronary artery disease (CAD) evaluated by convolutional neural networks (CNN) based coronary computed tomography angiography (CCTA). Methods: A total of 1796 consecutive inpatients with suspected CAD were evaluated by CCTA for CAD-RADS 1.0 and CAD-RADS 2.0 classifications. Kaplan-Meier and multivariate Cox models were used to estimate major adverse cardiovascular events (MACE) inclusive of all-cause mortality or myocardial infarction (MI). The C-statistic was used to assess the discriminatory ability of the two classifications. Results: In total, 94 (5.2%) MACE occurred over the median follow-up of 45.25 months (interquartile range 43.53-46.63 months). The annualized MACE rate was 0.014 (95% CI: 0.011-0.017). Kaplan-Meier survival curves indicated that the CAD-RADS classification, segment involvement score (SIS) grade, and Computed Tomography Fractional Flow Reserve (CT-FFR) classification were all significantly associated with the increase in the cumulative MACE (all P < 0.001). CAD-RADS classification, SIS grade, and CT-FFR classification were significantly associated with endpoint in univariate and multivariate Cox analysis. CAD-RADS 2.0 showed a further incremental increase in the prognostic value in predicting MACE (c-statistic 0.702, 95% CI: 0.641-0.763, P = 0.047), compared with CAD-RADS 1.0. Conclusions: The novel CAD-RADS 2.0 evaluated by CNN-based CCTA showed higher prognostic value of MACE than CAD-RADS 1.0 in patients with suspected CAD.

Alcanivorax xiamenensis sp. nov., a novel marine hydrocarbonoclastic bacterium isolated from surface seawater.

A novel Alcanivorax-related strain, designated 6-D-6T, was isolated from the surface seawater collected around Xiamen Island. The novel strain is Gram-stain-negative, rod-shaped and motile, and grows at 10-45 °C, pH 6.0-9.0 and in the presence of 0.5-15.0 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that it belongs to the genus Alcanivorax, with the highest sequence similarity to Alcanivorax dieselolei B5T (99.9 %), followed by Alcanivorax xenomutans JC109T (99.5 %), Alcanivorax balearicus MACL04T (99.3 %) and other 13 species of the genus Alcanivorax (93.8 %-95.6 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain 6-D-6T and three close type strains were 40.1-42.9/90.6-91.4 %, and others were below 22.9/85.1 %, respectively. The novel strain contained major cellular fatty acids of C16 : 0 (31.0 %), C19 : 0 ω8c cyclo (23.5 %), C17 : 0 cyclo (9.7 %), C12 : 0 3OH (8.6 %), summed feature 8 (7.6 %) and C12 : 0 (5.4 %). The genomic G+C content of strain 6-D-6T was 61.38 %. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified phospholipids and one amino-group-containing phospholipid were detected. On the basis of phenotypic and genotypic characteristics, strain 6-D-6T represents a novel species within the genus Alcanivorax, for which the name Alcanivorax xiamenensis sp. nov. is proposed. The type strain is 6-D-6T (=MCCC 1A01359T=KCTC 92480T).

Identification of a novel immune-related gene signature for prognosis and the tumor microenvironment in patients with uveal melanoma combining single-cell and bulk sequencing data.

Introduction: Uveal melanoma (UVM) is the most invasive intraocular malignancy in adults with a poor prognosis. Growing evidence revealed that immune-related gene is related to tumorigenesis and prognosis. This study aimed to construct an immune-related prognostic signature for UVM and clarify the molecular and immune classification. Methods: Based on The Cancer Genome Atlas (TCGA) database, single-sample gene set enrichment (ssGSEA) and hierarchical clustering analysis were performed to identify the immune infiltration pattern of UVM and classify patients into two immunity clusters. Then, we proposed univariate and multivariate Cox regression analysis to identify immune-related genes that related to overall survival (OS) and validated in the Gene Expression Omnibus (GEO) external validation cohort. The molecular and immune classification in the immune-related gene prognostic signature defined subgroups were analyzed. Results: The immune-related gene prognostic signature was constructed based on S100A13, MMP9, and SEMA3B genes. The prognostic value of this risk model was validated in three bulk RNA sequencing datasets and one single-cell sequencing dataset. Patients in the low-risk group had better OS than those in the high-risk group. The receiver-operating characteristic (ROC) analysis revealed its strong predictive ability for UVM patients. Lower expression of immune checkpoint genes was presented in the low-risk group. Functional studies showed that S100A13 knockdown via siRNA inhibited UVM cell proliferation, migration, and invasion in vitro, with the increased expression of reactive oxygen species (ROS) related markers in UVM cell lines. Discussion: The immune-related gene prognostic signature is an independent predictive factor for the survival of patients with UVM and provides new information about cancer immunotherapy in UVM.

Cyclin A participates in the TSO1-MYB3R1 regulatory module to maintain shoot meristem size and fertility in Arabidopsis.

The stem cell pools at the shoot apex and root tip give rise to all the above- and below-ground tissues of a plant. Previous studies in Arabidopsis identified a TSO1-MYB3R1 transcriptional module that controls the number and size of the stem cell pools at the shoot apex and root tip. As TSO1 and MYB3R1 are homologous to components of an animal cell cycle regulatory complex, DREAM, Arabidopsis mutants of TSO1 and MYB3R1 provide valuable tools for investigations into the link between cell cycle regulation and stem cell maintenance in plants. In this study, an Arabidopsis cyclin A gene, CYCA3;4, was identified as a member of the TSO1-MYB3R1 regulatory module and cyca3;4 mutations suppressed the tso1-1 mutant phenotype specifically in the shoot. The work reveals how the TSO1-MYB3R1 module is integrated with the cell cycle machinery to control cell division at the shoot meristem.

Paracrocinitomix mangrovi gen. nov., sp. nov., isolated from a mangrove sediment: proposal of two new families, Phaeocystidibacteraceae fam. nov. and Owenweeksiaceae fam. nov., and emended description of the family Schleiferiaceae.

A Gram-stain-negative and short rod-shaped bacterial strain designated GM2-3-6-6T was obtained from a mangrove sediment. Cells were light yellow-pigmented, catalase-positive and oxidase-positive. Carotenoid pigment was produced. Phylogeny of the 16S rRNA gene showed that strain GM2-3-6-6T was affiliated to the family Crocinitomicaceae, sharing maximum sequence similarities with Crocinitomix algicola 0182T, C. catalasitica IFO 15977T, and Putridiphycobacter roseus SM1701T of 93.8%, 93.6%, and 92.5%, respectively. The average nucleotide identity values, digital DNA-DNA hybridization estimates and average amino acid identity values between strain GM2-3-6-6T and the three close relatives were 68.6-68.8%, 18.5-19.2%, and 59.0-62.3%, respectively. The complete circular genome of strain GM2-3-6-6T was 4,365,762 bp in length with a DNA G + C content of 35.0%. The respiratory quinone was MK-7. The major polar lipids consisted of phosphatidylethanolamine, two unidentified phospholipids, one unidentified aminoglycolipid, one unidentified aminolipid and four other unidentified lipids. The major fatty acids were iso-C15:0, iso-C15:1 G, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and iso-C17:0 3-OH. Based on genomic, phenotypic, and chemotaxonomic characterizations, strain GM2-3-6-6T represents a novel species of a novel genus, for which the name Paracrocinitomix mangrovi gen. nov., sp. nov. is proposed. The type strain is GM2-3-6-6T (= MCCC 1K04831T = KCTC 82931T). Additionally, phylogenomic analysis of the type strains of the family Schleiferiaceae and family Cryomorphaceae related members including uncultivated bacteria, was performed using the Genome Taxonomic Database toolkit (GTDB-Tk). Based on 16S rRNA gene phylogeny and genomic features, two novel families, Phaeocystidibacteraceae fam. nov. and Owenweeksiaceae fam. nov. are proposed. An emended description of the family Schleiferiaceae is also proposed.

CRISPR/Cas9-Mediated Multiple Knockouts in Abscisic Acid Receptor Genes Reduced the Sensitivity to ABA during Soybean Seed Germination.

Abscisic acid (ABA) is an important plant hormone that regulates numerous functions in plant growth, development, and stress responses. Several proteins regulate the ABA signal transduction mechanism in response to environmental stress. Among them, the PYR1/PYL/RCAR family act as ABA receptors. This study used the CRISPR/Cas9 gene-editing system with a single gRNA to knock out three soybean PYL genes: GmPYL17, GmPYL18, and GmPYL19. The gRNA may efficiently cause varying degrees of deletion of GmPYL17, GmPYL18, and GmPYL19 gene target sequences, according to the genotyping results of T0 plants. A subset of induced alleles was successfully transferred to progeny. In the T2 generation, we obtained double and triple mutant genotypes. At the seed germination stage, CRISPR/Cas9-created GmPYL gene knockout mutants, particularly gmpyl17/19 double mutants, are less susceptible to ABA than the wild type. RNA-Seq was used to investigate the differentially expressed genes related to the ABA response from germinated seedlings under diverse treatments using three biological replicates. The gmpyl17/19-1 double mutant was less susceptible to ABA during seed germination, and mutant plant height and branch number were higher than the wild type. Under ABA stress, the GO enrichment analysis showed that certain positive germination regulators were activated, which reduced ABA sensitivity and enhanced seed germination. This research gives a theoretical basis for a better understanding of the ABA signaling pathway and the participation of the key component at their molecular level, which helps enhance soybean abiotic stress tolerance. Furthermore, this research will aid breeders in regulating and improving soybean production and quality under various stress conditions.

High-Resolution Small RNAs Landscape Provides Insights into Alkane Adaptation in the Marine Alkane-Degrader Alcanivorax dieselolei B-5

Alkanes are widespread in the ocean, and Alcanivorax is one of the most ubiquitous alkane-degrading bacteria in the marine ecosystem. Small RNAs (sRNAs) are usually at the heart of regulatory pathways, but sRNA-mediated alkane metabolic adaptability still remains largely unknown due to the difficulties of identification. Here, differential RNA sequencing (dRNA-seq) modified with a size selection (~50-nt to 500-nt) strategy was used to generate high-resolution sRNAs profiling in the model species Alcanivorax dieselolei B-5 under alkane (n-hexadecane) and non-alkane (acetate) conditions. As a result, we identified 549 sRNA candidates at single-nucleotide resolution of 5'-ends, 63.4% of which are with transcription start sites (TSSs), and 36.6% of which are with processing sites (PSSs) at the 5'-ends. These sRNAs originate from almost any location in the genome, regardless of intragenic (65.8%), antisense (20.6%) and intergenic (6.2%) regions, and RNase E may function in the maturation of sRNAs. Most sRNAs locally distribute across the 15 reference genomes of Alcanivorax, and only 7.5% of sRNAs are broadly conserved in this genus. Expression responses to the alkane of several core conserved sRNAs, including 6S RNA, M1 RNA and tmRNA, indicate that they may participate in alkane metabolisms and result in more actively global transcription, RNA processing and stresses mitigation. Two novel CsrA-related sRNAs are identified, which may be involved in the translational activation of alkane metabolism-related genes by sequestering the global repressor CsrA. The relationships of sRNAs with the characterized genes of alkane sensing (ompS), chemotaxis (mcp, cheR, cheW2), transporting (ompT1, ompT2, ompT3) and hydroxylation (alkB1, alkB2, almA) were created based on the genome-wide predicted sRNA-mRNA interactions. Overall, the sRNA landscape lays the ground for uncovering cryptic regulations in critical marine bacterium, among which both the core and species-specific sRNAs are implicated in the alkane adaptive metabolisms.

Effect of pinch types on pinch force sense in healthy adults.

Pinch force sense plays an important role in the performance of daily finger movements, including tip, key, palmar pinch. The present study investigated the roles of pinch type in the sensation of pinch force among healthy participants in the ipsilateral force reproduction trial. This study instructed forty healthy adult subjects (20 women and 20 men) in producing reference forces at different levels [10, 30, 50% maximal voluntary isometric contraction (MVIC)] by adopting 3 pinch types (tip, key, and palmar pinches) and in reproducing the above force levels with the identical hand. Our study revealed that subjects are significantly more sensitive detecting alterations of pinching forces with tip pinch but not key or palmar pinch under high forces (30 and 50% MVIC) but not at lower force levels (10% MVIC).

Aestuarium zhoushanense is a later heterotypic synonym of Marivivens donghaensis, and transfer of Paradonghicola geojensis to the genus Marivivens as Marivivens geojensis comb. nov.

The 16S rRNA genes of Aestuarium zhoushanense G7T and Paradonghicola geojensis FJ12T shared 100 % sequence identity with Marivivens donghaensis AM-4T. Phylogeny of 16S rRNA gene sequences showed that the three type strains formed a monophyletic clade within the genus Marivivens. Whole genome sequence comparisons showed that three type strains shared 46.7-69.7 % digital DNA-DNA hybridization, 92.1-96.4 % average nucleotide identity and 96.2-98.1 % average amino acid identity. The high 16S rRNA gene similarity values show that three type strains should belong to the same genus. The pan-genome of the five strains contained 5754 genes including 1877 core genes. Based on the principle of priority, we propose that A. zhoushanense Yu et al. 2019 is a later heterotypic synonym of M. donghaensis Park et al. 2016, and P. geojensis should be reclassified as Marivivens geojensis comb. nov., respectively.

The prognostic value of immune-related genes AZGP1, SLCO5A1, and CTF1 in Uveal melanoma.

Objective: Uveal melanoma (UM) is an aggressive malignancy with a poor prognosis and no available effective treatment. Therefore, exploring a potential prognostic marker for UM could provide new possibilities for early detection, recurrence, and treatment. Methods: In this study, we used "ConsensusClusterPlus" to classify patients with UM into subgroups, screened for significant differences in immune prognostic factors between subgroups, selected three genes using LASSO (Least absolute shrinkage and selection operator) regression to construct a risk model, and performed tumor immune cell infiltration analysis on the risk model. infiltration analysis, and then verified the heterogeneous role of the 3 core genes in other cancers by pan-cancer analysis and validate its expression by RT-qPCR in normal and tumor cells. Results: We consistently categorized 80 UM patients into two subgroups after the immunogenetic set, where the UM1 subgroup had a better prognosis than the UM2 subgroup, and used 3 immune-related genes AZGP1, SLCO5A1, and CTF1 to derive risk scores as independent prognostic markers and predictors of UM clinicopathological features. We found significant differences in overall survival (OS) between low- and high-risk groups, and prognostic models were negatively correlated with B cell and myeloid dendritic cell and positively correlated with CD8+ T cell AZGP1 and CTF1 were significantly upregulated in UM cells compared with normal UM cells. Conclusion: Immunogens are significantly associated with the prognosis of UM, and further classification based on genetic characteristics may help to develop immunotherapeutic strategies and provide new approaches to develop customized treatment strategies for patients.

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas.

Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell-cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immune-related pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.

A novel contrast-induced acute kidney injury mouse model based on low-osmolar contrast medium.

The contrast-induced acute kidney injury (CI-AKI) has been becoming the third common cause of hospital-acquired acute kidney injury. An ideal animal model is essential for understanding the pathophysiology of CI-AKI. Previous CI-AKI studies were mostly performed on rats with high-osmolar contrast medium (HOCM), which is unsuitable for transgenic researches. This study provides a novel, efficient and reproducible CI-AKI model which was developed in mouse by administrating a low-osmolar contrast medium (LOCM). First of all, we applied the frequently used pretreatments (uninephrectomy and water deprivation), which combined with HOCM on rats could induce CI-AKI, on mice with LOCM. Secondly, we attempted to find a novel pretreatment suitable for mouse and LOCM by combining two classic pretreatments(uninephrectomy, water deprivation and furosemide administration). Finally, we evaluate the kidney damage of the novel model. We found that this mouse model possessed a significant reduction in renal function, severe renal tissue damage, and increased renal tubular cells apoptosis, indicating that LOCM is a feasible inducer for CI-AKI mice model. Taken together, we found that uninephrectomy (UPHT) combined with 24 h water deprivation and furosemide administration 20 min before LOCM (iohexol, 10 ml/kg) application is a feasible pretreatment to establish a novel CI-AKI mouse model.

Pelagibacterium xiamenense sp. nov., isolated from intertidal sediment.

A Gram-stain-negative, obligately aerobic bacterium, designated as HS1C4-1T, was isolated from a sediment sample from the tidal zone of the Haicang Coast, Xiamen, Fujian Province, PR China. The strain was yellowish-coloured, non-gliding, rod-shaped and motile, with a single polar flagellum. Cells of HS1C4-1T were oxidase- and catalase-positive. The strain could grow at 15-55 °C (optimum 37 °C), pH 6.0-10.0 (optimum, pH 7.0-9.0), in the presence of 0-12 % (optimum, 1 %) NaCl (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that HS1C4-1T represented a member of the genus Pelagibacterium, and shared the highest similarity to Pelagibacterium luteolum CGMCC 1.10267T (97.6 %). Digital DNA-DNA hybridization values and average nucleotide identity between HS1C4-1T and all the species of genus Pelagibacterium were 18.7-20.2 % and 77.3-78.4 %, respectively. The principal fatty acids (>10 %) were C19 : 0 cyclo ω8c (50.5 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 29.1%). Q-10 was the sole respiratory quinone. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and six unidentified lipids. The G+C content of the chromosomal DNA was 62.9 %. On the basis of phylogenetic, phenotypic, chemotaxonomic and genomic characteristics, HS1C4-1T represents a novel species within the genus Pelagibacterium, for which the name Pelagibacterium xiamenense sp. nov. is proposed. The type strain is HS1C4-1T (=MCCC 1A18759T=KCTC 92097T).