Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.

INTRODUCTION: Exaggerated neutrophil recruitment and activation are the major features of pathological alterations in periodontitis, in which neutrophil extracellular traps (NETs) are considered to be responsible for inflammatory periodontal lesions. Despite the critical role of NETs in the development and progression of periodontitis, their specific functions and mechanisms remain unclear. OBJECTIVES: To demonstrate the important functions and specific mechanisms of NETs involved in periodontal immunopathology. METHODS: We performed single-cell RNA sequencing on gingival tissues from both healthy individuals and patients diagnosed with periodontitis. High-dimensional weighted gene co-expression network analysis and pseudotime analysis were then applied to characterize the heterogeneity of neutrophils. Animal models of periodontitis were treated with NETs inhibitors to investigate the effects of NETs in severe periodontitis. Additionally, we established a periodontitis prediction model based on NETs-related genes using six types of machine learning methods. Cell-cell communication analysis was used to identify ligand-receptor pairs among the major cell groups within the immune microenvironment. RESULTS: We constructed a single-cell atlas of the periodontal microenvironment and obtained nine major cell populations. We further identified a NETs-related subgroup (NrNeu) in neutrophils. An in vivo inhibition experiment confirmed the involvement of NETs in gingival inflammatory infiltration and alveolar bone absorption in severe periodontitis. We further screened three key NETs-related genes (PTGS2, MME and SLC2A3) and verified that they have the potential to predict periodontitis. Moreover, our findings revealed that gingival fibroblasts had the most interactions with NrNeu and that they might facilitate the production of NETs through the MIF-CD74/CXCR4 axis in periodontitis. CONCLUSION: This study highlights the pathogenic role of NETs in periodontal immunity and elucidates the specific regulatory relationship by which gingival fibroblasts activate NETs, which provides new insights into the clinical diagnosis and treatment of periodontitis.

Genome-wide analysis revealed the dysregulation of RNA binding protein-correlated alternative splicing events in myocardial ischemia reperfusion injury.

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI), the tissue damage which is caused by the returning of blood supply to tissue after a period of ischemia, greatly reduces the therapeutic effect of treatment of myocardial infarction. But the underlying functional mechanisms of MIRI are still unclear. METHODS: We constructed mouse models of MIRI, extracted injured and healthy myocardial tissues, and performed transcriptome sequencing experiments (RNA-seq) to systematically investigate the dysregulated transcriptome of MIRI, especially the alternative splicing (AS) regulation and RNA binding proteins (RBPs). Selected RBPs and MIRI-associated AS events were then validated by RT-qPCR experiments. RESULTS: The differentially expressed gene (DEG) analyses indicated that transcriptome profiles were changed by MIRI and that DEGs' enriched functions were consistent with MIRI's dysregulated pathways. Furthermore, the AS profile was synergistically regulated and showed clear differences between the mouse model and the healthy samples. The exon skipping events significantly increased in MIRI model samples, while the opposite cassette exon events significantly decreased. According to the functional analysis, regulated alternative splicing genes (RASGs) were enriched in protein transport, cell division /cell cycle, RNA splicing, and endocytosis pathways, which were associated with the development of MIRI. Meanwhile, 493 differentially expressed RBPs (DE RBPs) were detected, most of which were correlated with the changed ratios of AS events. In addition, nine DE RBP genes were validated, including Eif5, Pdia6, Tagln2, Vasp, Zfp36l2, Grsf1, Idh2, Ndrg2, and Uqcrc1. These nine DE RBPs were correlated with RASGs enriched in translation process, cell growth and division, and endocytosis pathways, highly consistent with the functions of all RASGs. Finally, we validated the AS ratio changes of five regulated alternative splicing events (RASEs) derived from important regulatory genes, including Mtmr3, Cdc42, Cd47, Fbln2, Vegfa, and Fhl2. CONCLUSION: Our study emphasized the critical roles of the dysregulated AS profiles in MIRI development, investigated the potential functions of MIRI-associated RASGs, and identified regulatory RBPs involved in AS regulation. We propose that the identified RASEs and RBPs could serve as important regulators and potential therapeutic targets in MIRI treatment in the future.

A Survey of Optimization Methods for Independent Vector Analysis in Audio Source Separation.

With the advent of the era of big data information, artificial intelligence (AI) methods have become extremely promising and attractive. It has become extremely important to extract useful signals by decomposing various mixed signals through blind source separation (BSS). BSS has been proven to have prominent applications in multichannel audio processing. For multichannel speech signals, independent component analysis (ICA) requires a certain statistical independence of source signals and other conditions to allow blind separation. independent vector analysis (IVA) is an extension of ICA for the simultaneous separation of multiple parallel mixed signals. IVA solves the problem of arrangement ambiguity caused by independent component analysis by exploiting the dependencies between source signal components and plays a crucial role in dealing with the problem of convolutional blind signal separation. So far, many researchers have made great contributions to the improvement of this algorithm by adopting different methods to optimize the update rules of the algorithm, accelerate the convergence speed of the algorithm, enhance the separation performance of the algorithm, and adapt to different application scenarios. This meaningful and attractive research work prompted us to conduct a comprehensive survey of this field. This paper briefly reviews the basic principles of the BSS problem, ICA, and IVA and focuses on the existing IVA-based optimization update rule techniques. Additionally, the experimental results show that the AuxIVA-IPA method has the best performance in the deterministic environment, followed by AuxIVA-IP2, and the OverIVA-IP2 has the best performance in the overdetermined environment. The performance of the IVA-NG method is not very optimistic in all environments.

Global, Regional, and National Burdens of Ischemic Heart Disease Attributable to Smoking From 1990 to 2019.

Background This study was conducted to estimate the distribution of and changes in the global disease burden of ischemic heart disease attributable to smoking between 1990 and 2019. Methods and Results Data used in this study come from the GBD 2019 (Global Burden of Disease Study 2019). Age-standardized rates and estimated annual percentage change of age-standardized rates were used to describe this burden and its changing trend. Pearson's correlation coefficient was used to evaluate the correlation between the sociodemographic index and changing trend. From 1990 to 2019, the burden of ischemic heart disease attributable to smoking has shown a downward trend globally; estimated annual percentage changes of age-standardized mortality rates and age-standardized disability-adjusted life-years rates were -2.012 (95% CI, -2.068 to -1.956) and -1.907 (95% CI, -1.975 to -1.838). Nineteen countries experienced an increase in disease burden, and the changes in 17 countries were not statistically significant. In addition, this burden was higher in men and older age groups. Estimated annual percentage change of the age-standardized rates of this burden were negatively correlated with the sociodemographic index. Conclusions Although the burden of ischemic heart disease attributable to smoking has decreased in >80% of countries or regions in the past 30 years, it has remained a significant issue in low- and middle-income countries, particularly among men and elderly populations. Therefore, active tobacco control measures, focusing on key populations, are required to reduce the associated burden of ischemic heart disease, especially in those countries or regions with increasing prevalence and disease burden.

Robust sparse reconstruction of attenuated acoustic field with unknown range of source.

In this paper, we present a gridless algorithm to recover an attenuated acoustic field without knowing the range information of the source. This algorithm provides the joint estimation of horizontal wavenumbers, mode amplitudes, and acoustic attenuation. The key idea is to approximate the acoustic field in range as a finite sum of damped sinusoids, for which the sinusoidal parameters convey the ocean information of interest (e.g., wavenumber, attenuation, etc.). Using an efficient finite rate of innovation algorithm, an accurate recovery of the attenuated acoustic field can be achieved, even if the measurement noise is correlated and the range of the source is unknown. Moreover, the proposed method is able to perform joint recovery of multiple sensor data, which leads to a more robust field reconstruction. The data used here are acquired from a vertical line array at different depths measuring a moving source at several ranges. We demonstrate the performance of the proposed algorithm both in synthetic simulations and real shallow water evaluation cell experiment 1996 data.

The diagnostic significance of integrating m6A modification and immune microenvironment features based on bioinformatic investigation in aortic dissection.

Purpose: The aim of this study was to investigate the role of m6A modification and the immune microenvironment (IME) features in aortic dissection (AD) and establish a clinical diagnostic model for AD based on m6A and IME factors. Methods: GSE52093, GSE98770, GSE147026, GSE153434, and GSE107844 datasets were downloaded from the GEO database. The expression of 21 m6A genes including m6A writers, erasers, readers, and immune cell infiltrates was analyzed in AD and healthy samples by differential analysis and ssGSEA method, respectively. Both correlation analyses between m6A genes and immune cells were conducted by Pearson and Spearman analysis. XGboost was used to dissect the major m6A genes with significant influences on AD. AD samples were classified into two subgroups via consensus cluster and principal component analysis (PCA) analysis, respectively. Among each subgroup, paramount IME features were evaluated. Random forest (RF) was used to figure out key genes from AD and healthy shared differentially expressed genes (DEGs) and two AD subgroups after gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, we constructed an AD diagnostic model combining important m6A regulatory genes and assessed its efficacy. Results: Among 21 m6A genes, WTAP, HNRNPC, and FTO were upregulated in AD samples, while IGF2BP1 was downregulated compared with healthy samples. Immune cell infiltrating analysis revealed that YTHDF1 was positively correlated with γδT cell level, while FTO was negatively correlated with activated CD4+ T cell abundance. FTO and IGF2BP1 were identified to be crucial genes that facilitate AD development according to the XGboost algorithm. Notably, patients with AD could be classified into two subgroups among which 21 m6A gene expression profiles and IME features differ from each other via consensus cluster analysis. The RF identified SYNC and MAPK1IP1L as the crucial genes from common 657 shared common genes in 1,141 DEGs between high and low m6A scores of AD groups. Interestingly, the AD diagnostic model coordinating SYNC and MAPK1IP1L with FTO and IGF2BP1 performed well in distinguishing AD samples. Conclusion: This study indicated that FTO and IGF2BP1 were involved in the IME of AD. Integrating FTO and IGF2BP1 and MAPK1IP1L key genes in AD with a high m6A level context would provide clues for forthcoming AD diagnosis and therapy.

Identification of nine signature proteins involved in periodontitis by integrated analysis of TMT proteomics and transcriptomics.

Recently, there are many researches on signature molecules of periodontitis derived from different periodontal tissues to determine the disease occurrence and development, and deepen the understanding of this complex disease. Among them, a variety of omics techniques have been utilized to analyze periodontitis pathology and progression. However, few accurate signature molecules are known and available. Herein, we aimed to screened and identified signature molecules suitable for distinguishing periodontitis patients using machine learning models by integrated analysis of TMT proteomics and transcriptomics with the purpose of finding novel prediction or diagnosis targets. Differential protein profiles, functional enrichment analysis, and protein-protein interaction network analysis were conducted based on TMT proteomics of 15 gingival tissues from healthy and periodontitis patients. DEPs correlating with periodontitis were screened using LASSO regression. We constructed a new diagnostic model using an artificial neural network (ANN) and verified its efficacy based on periodontitis transcriptomics datasets (GSE10334 and GSE16134). Western blotting validated expression levels of hub DEPs. TMT proteomics revealed 5658 proteins and 115 DEPs, and the 115 DEPs are closely related to inflammation and immune activity. Nine hub DEPs were screened by LASSO, and the ANN model distinguished healthy from periodontitis patients. The model showed satisfactory classification ability for both training (AUC=0.972) and validation (AUC=0.881) cohorts by ROC analysis. Expression levels of the 9 hub DEPs were validated and consistent with TMT proteomics quantitation. Our work reveals that nine hub DEPs in gingival tissues are closely related to the occurrence and progression of periodontitis and are potential signature molecules involved in periodontitis.

The fate of concomitant mild mitral regurgitation in aortic insufficiency: A neglected subject.

Objectives: Mitral regurgitation (MR) is commonly experienced by patients with aortic insufficiency (AI), and in its mild form, it is considered benign. However, the progression of concomitant mild regurgitation after the aortic valve surgery (AVS) for AI is poorly characterized. The current study aimed to define the long-term outcomes of MR after surgery and identify the risk factors involved in deterioration. Methods: Patients presenting with moderate/severe AI and concomitant mild MR (n = 347) between January 2013 and December 2021 were enrolled. MR grade was assessed by transthoracic echocardiography during the follow-up, and deterioration is defined as an increase in grade to moderate or severe MR from the previous follow-up echocardiography. Analysis of risk factors for early mortality, MR deterioration, and long-term mortality was performed. Results: A total of 278 patients (84.8%) among 328 survivors had at least one follow-up echocardiography, and complete follow-up occurred for 316 patients (96.3%). Mild MR improved to trivial or none in 194 patients (69.8%), progressed to persistent mild MR for 74 patients (26.6%), and deteriorated for 10 patients (3.6%). Preoperative atrial fibrillation [odds ratio (OR), 23.09; 95% confidence interval (CI), 4.35-122.54] and rheumatic AI (OR, 11.61; 95% CI, 1.26-106.85) were shown to be independent risk factors for MR deterioration by generalized linear mixed analysis. Conclusion: Progression of concomitant mild MR is rare in patients with AI after AVS. However, rheumatic AI and preoperative atrial fibrillation increase the probability of MR deterioration. Careful follow-up for this cohort of patients is recommended.

Intrinsic left ventricular impairment in Marfan syndrome: A systematic review and meta-analysis.

BACKGROUND: Intrinsic cardiac impairment in Marfan syndrome (MFS) has been explored in many clinical studies; however, their results have been inconsistent. This meta-analysis aimed to assess the difference in cardiac structure and function between Marfan patients and healthy individuals, and to verify the hypothesis of intrinsic cardiac impairment in MFS. METHODS: Electronic searches for studies were performed in the PubMed, Embase, and Cochrane Library databases. Nine studies with 490 patients with MFS and 478 controls were included in the analysis. Age and sex were strictly matched between Marfan patients and healthy controls in every study. RESULTS: There was no difference in the left ventricular end systolic diameter index (mean difference [MD]: 0.33; 95% confidence interval [CI]: (-0.24, 0.89); p = 0.26) and left ventricular end diastolic diameter index (MD: 0.18; 95% CI: [-0.47, 0.83]; p = 0.58) between Marfan patients and controls. Marfan patients showed larger left ventricular end systolic volume index (MD: 2.62; 95% CI: [0.27, 4.97]; p = 0.03) and left ventricular end diastolic volume index (MD: 4.16; 95% CI: [2.70, 5.63]; p < 0.01) than the control group. Furthermore, Marfan patients showed a lower left ventricular ejection fraction than healthy people (MD: -2.59%; 95% CI: [-4.64%, -0.54%]; p = 0.01). CONCLUSIONS: Intrinsic cardiac impairment was observed in MFS. MFS patients showed the larger left ventricular volume and poorer left ventricular function than matched controls. Considering the potentially adverse impact on cardiac function, intrinsic cardiac impairment in MFS should be considered during the cardiac surgery.

MicroRNA-128-3p Enhances the Chemosensitivity of Temozolomide in Glioblastoma by Targeting c-Met and EMT.

Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Recent studies have demonstrated that miRNAs are closely related to resistance to cancer chemotherapy. This study aimed to further validate the biological role of miR-128-3p and to investigate whether miR-128-3p can enhance the chemosensitivity of glioblastoma to temozolomide (TMZ) and the underlying mechanisms. The effects of miR-128-3p and TMZ on the proliferation of glioblastoma cells were investigated by cell counting kit-8 (cck8). Transwell and intracerebral invasion assays were applied to determine the effects of the combination of miR-128-3p and TMZ on the invasion and migration of glioblastoma in vitro and in vivo. Flow cytometry was used to detect apoptosis in each group, and immunofluorescence was used to determine the expression levels of EMT-related proteins. RT-PCR and Western-blot were applied to detect EMT-transformed proteins (c-Met, PDGFRα, Notch1, and Slug) and EMT phenotype-associated proteins (Vim, CD44, and E-cadherin) at both mRNA and protein levels. Based on the microRNA.org database, we predicted the target genes of miR-128-3p. The target-relationship between miR-128-3p and c-Met and PDGFRα was verified by dual luciferase reporter gene. The tumor volume, weight and the expression levels of the proteins described above were measured in subcutaneously transplanted tumor model in nude mice. We found that the expression of miR-128-3p was down-regulated in glioblastoma tissue samples and cell lines. miR-128-3p suppressed the proliferation, migration, and invasion of GBM both in vitro and in vivo; miR-128-3p enhanced the therapeutic effect of TMZ via inhibition of proliferation, invasion and migration of glioblastoma cells and induction of apoptosis. Overexpression of miR-128-3p down-regulated the expression levels of EMT-transformed proteins (c-Met, PDGFRα, Notch1 and Slug) to enhance the effect of TMZ. In addition, we found that miR-128-3p targeted and bound c-Met. More importantly, the upregulation of c-Met significantly prompted U87 and U251 cell proliferation. This effect could be abolished when c-Met was silenced. The investigation in tumor bearing nude mice showed that miR-128-3p in combination with TMZ reduced tumor volume and the invasion extent, and increased the sensitivity of glioblastoma to TMZ. miR-128-3p is capable of enhancing the sensitivity of glioblastoma to TMZ through regulating c-Met/EMT.

A verification of correlation between chemical monitoring and multi-biomarker approach using clam Ruditapes philippinarum and scallop Chlamys farreri to assess the impact of pollution in Shandong coastal area of China.

Biogeochemical monitoring coupled with multi-biomarker approach were performed for the assessment of marine environment, using clam Ruditapes philippinarum and scallop Chlamys farreri to indicate contamination status in sediments and seawater respectively. The bivalves were collected from three stations, Jiaozhou Bay, Rushan Bay and Laizhou Bay, of Shandong coastal area. A series of contaminants (PAHs and TBBPA) and biomarkers (AhR, EROD, GST, SOD, GPx, CAT, DNA damage) were measured. Multi-biomarker pollution index (MPI) and integrated biomarker response (IBR) were carried out to evaluate contamination status and both indexes showed that Rushan Bay was most polluted, where the pollution level of sediments reached "highly polluted" in August, followed by Jiaozhou Bay and Rushan Bay which reached "lightly polluted". The correlation of IBR values with contaminants' concentrations was verified through the Pearson correlation coefficient (p < 0.05), consolidating this scientific assessment method for marine environment.

Microarray expression profiles and bioinformatics analysis of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma.

Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in three pairs of secondary temozolomide-resistant glioblastoma (STRG) and matched primary glioblastoma tissues by microarrays. Using these data, we discovered a total of 92 mRNA, 299 lncRNAs and 53 circRNAs were altered in human glioma tissue after chemotherapy with temozolomide. The functions of differentially expressed lncRNAs, circRNAs were annotated by analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The results showed that the highest enriched GO terms of the upregulated lncRNAs were embryonic forelimb morphogenesis (BP), extracellular space (CC), and serine-type endopeptidase activity (MF). Meanwhile, GO:0035360(BP), PRC1 complex (CC), and ubiquitin-protein transferase activity (MF) were the highest enriched GO terms targeted by downregulated lncRNAs. The NF-kappa B signaling pathway were significantly enriched in the STRG. However, circRNAs highest enriched GO term was viral process, chromosome, and protein transporter activity, respectively. KEGG pathway analysis showed that circRNAs in the network were enriched in ErbB signaling pathway. Furthermore, we also predicted the potential role of these differentially expressed ncRNAs and constructed a network of lncRNAs-mRNAs and circRNAs-miRNAs to show their interactions. After a series of bioinformatics analyses, we found that low expression of NONHSAT163779 and high expression of circ_0043949 are closely related to the chemoresistance of STRG. Our findings revealed the alteration of expression patterns of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma for the first time. NONHSAT163779 and hsa_circ_0043949 might be potential therapeutic targets and prognostic biomarkers for the treatment of glioblastoma.

Brain perivascular macrophages: Recent advances and implications in health and diseases.

Brain perivascular macrophages (PVMs) belong to a distinct population of brain-resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood-brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aß pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain-resident immune system, actively participate in a broad-spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.

A likely protective effect of dimethyl itaconate on cerebral ischemia/reperfusion injury.

As a membrane-permeable derivative of itaconate, dimethyl itaconate (DMI) was recently showed to limit inflammatory response of activated macrophages, and to decrease the generation of reactive oxygen species and reduce cardiac ischemia/reperfusion injury. However, the effect of DMI in the context of cerebral ischemia/reperfusion injury remains unclear. Here, we treated the transient middle cerebral artery occlusion (tMCAO) mice with DMI or saline at the beginning of occlusion, and allowed them to recover for 3 days. We found that DMI obviously decreased the neurologic deficit score. Further, DMI significantly inhibited the toxic conversion of the peri-infarct microglia, and decreased the protein level of interleukin 1ß. The present findings suggest that DMI might be recognized as a promising candidate for the treatment of ischemic stroke.

Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes.

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/ß-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.

Using multi-integrated biomarker indexes approach to assess marine quality and health status of marine organism: a case study of Ruditapes philippinarum in Laizhou Bay, China.

With the progress of technology and the deepening of understanding of biological monitoring, much more attention has been paid to the multiple evaluation of marine pollution monitoring. In view of this, our study aimed at establishing a multi-integrated biomarker indexes approach to evaluate marine condition systematically and comprehensively. In the current study, sampling was conducted in Laizhou Bay, China (S1, S2, and S3) in May, August, and October of 2015. And then, multi-integrated biomarker indexes approach was applied to assess marine PAHs pollution, select appropriate biomarkers, and evaluate marine environmental quality and health status of the clams of Ruditapes philippinarum. As the results showed, S2 was the most PAHs-polluted site while S1 was the least polluted site, and the levels of tPAHs in seawater and sediments ranged from 69.78 to 315.30 ng/L and 163.19 to 565.17 ng/g d.w., respectively. And all three sampling sites had different sources of PAHs. IBR represented DNA damage (F value), the expression of SOD, EROD activity, GST activity, and LPO could be served as biomarkers to monitor the PAHs pollution in Laizhou Bay. And MPI suggested the quality of all three sites: S1 was generally favorable, S2 was moderately polluted, and S3 was lightly polluted. BRI values showed that the order of health status of R. philippinarum was S1 > S3 > S2.

Overexpression of CLEC18B Associates With the Proliferation, Migration, and Prognosis of Glioblastoma.

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients' prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan-Meier survival and the Cox proportional hazard model. The role of CLEC18B in GBM was determined by loss-of-function assay using small interfering RNA approach in vitro. Functional and signaling analyses were also performed to understand how CLEC18B facilitated the aggressiveness of GBM at molecular and cellular levels using Cell Counting Kit-8 assay, wound-healing, transwell, and Western blot analyses. Results from our analyses showed that CLEC18B was markedly elevated in both GBM tissues and cells, and exhibited strong inverse correlation with overall survival in GBM patients. Moreover, CLEC18B was identified as an independent predictor of patient survival. Functionally, knockdown of CLEC18B inhibited the growth, migration, and invasion of GBM cells. Mechanistic studies revealed that silencing of CLEC18B resulted in downregulation of Wnt/ß-catenin signaling activity. Collectively, our findings provide clinical, molecular, and cellular evidence of CLEC18B as a promising prognostic biomarker and therapeutic target for GBM.

Expression profiles of different glutathione S-transferase isoforms in scallop Chlamys farreri exposed to benzo[a]pyrene and chrysene in combination and alone.

Aquatic organisms are increasingly exposed to polycyclic aromatic hydrocarbons (PAHs) due to anthropogenic pressure. This study aimed at evaluating the response of Glutathione S-transferases (GSTs) in scallop Chlamys farreri against benzo[a]pyrene (BaP) and chrysene (CHR) exposure under laboratory conditions. Nine published GST genes were classified into six subfamilies and a new member of rho family was identified for the first time. Twelve GSTs (including nine published GST genes and three in transcriptome established by our laboratory) mRNA transcript levels in the gills, digestive glands, adductor muscle, mantle, testis, ovaries, blood cells of scallops were measured by real-time PCR. The results showed that the mRNA transcript levels of twelve GSTs, except GST-zeta, GST-mu and GST-microsomal, were highest in digestive gland. Accordingly, the mRNA expression levels of GSTs were measured in digestive glands of scallops exposed to BaP (0.1µg/L and 1µg/L), CHR (0.1µg/L and 1µg/L) and their mixtures (0.1µg/L BaP +0.1µg/L CHR and 1µg/L BaP +1µg/L CHR). The results indicated that different GST had specific response to different pollution exposure. In BaP exposure experiment, the mRNA expression level of GST-theta was a potential suitable biomarker. GST-sigma-2 and GST-3, which belonged to sigma class, were sensitive to CHR exposure while GST-microsomal was considered a potential ideal bioindicator to joint exposure of BaP and CHR. In summary, this study investigated the classification of GSTs and provided information about the expression profiles of different class GSTs after PAHs exposure.

Assessing PAHs pollution in Shandong coastal area (China) by combination of chemical analysis and responses of reproductive toxicity in crab Portunus trituberculatus.

The concentrations of PAHs in seawater and sediments were measured at three selected sites (S1, S2, and S3) along the coastal area of Shandong (China) in April, May, and June, 2015, which ranged from 29.72 to 123.88 ng/L and 82.62 to 232.63 ng/g, respectively. Meanwhile, the reproductive toxicity responses in crab Portunus trituberculatus were also evaluated to assess the pollution of PAHs during the sampling period. Chemical analysis showed that S3 was the most PAH-contaminated area while S1 was the least, and the biochemical parameters concerned with reproduction were efficiently responded to the three sites, especially in S3 (p < 0.05). Moreover, the principal component analyses (PCA) showed that parameters for DNA alkaline unwinding, protein carbonyl content, and lipid peroxidation levels in two genders, 17ß-estradiol in female, testosterone and TESK2 gene expression in male crabs, were closely correlated with the concentrations of PAHs (2 + 3 rings, 4 rings, and 5 + 6 rings), which were considered to be good candidate indicators to assess the environmental pollutions resulting from PAHs in the coastal area of Shandong, China.

A multi-biomarker approach in scallop Chlamys farreri to assess the impact of contaminants in Qingdao coastal area of China.

A multi-biomarker approach was carried out to classify the environmental quality and the adverse effects of contaminants on scallop Chlamys farreri. The scallops were collected from three sampling stations in Qingdao coastal area of China in March, May, August and October of 2015. A suite of environmental factors and biomarkers, including temperature, salinity, pH, the concentrations of polycyclic aromatic hydrocarbons (PAHs), tetrabromobisphenol A (TBBPA) and metals (Cr, Mn, Cu, Zn, Cd, Pb, As) in seawater and soft tissue, mRNA expression of aryl hydrocarbon receptor (AhR) and P-glycoprotein (P-gp), 7-ethoxyresorufin O-deethylase (EROD), glutathione-S-transferase (GST), uridine-diphosphate-glucuronyl-transferase (UGT), sulfotransferase (SULT), metallothionein (MT), Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation (LPO) and protein carbonyl (PC) contents and DNA strand breaks, were measured in the gill and digestive gland. The results showed that S2 was the most polluted while S1 was identified the least polluted. Despite the differentiation of pollution levels and environmental parameters the selected biomarkers responded efficiently to contaminants. Principal component analysis (PCA) revealed that EROD for PAHs, AhR for TBBPA, MT for Cr, Pb and Mn, LPO and PC for Zn were the effective biomarkers respectively. This study demonstrated that the application of multi-biomarker approach in conjunction with the traditional analysis of environmental parameters and contaminants provided valuable information in environmental risk assessment.