Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

Trace element levels in the muscles of three tern species (Aves: Laridae) from the western Arabian Gulf: environmental assessment and implications for conservation.

In the Arabian Gulf (called also Persian Gulf; hereafter 'the Gulf'), Jana and Karan Islands are recognized as one of the most Important Bird Areas in the region. Many migratory breeding seabirds, like the Greater Crested Tern Thalasseus bergii, White-cheeked Tern Sterna repressa and Bridled Tern Onychoprion anaethetus, depend on these islands during the breeding season. However, these aquatic wildlife species are suffering from intensified urban and industrial coastal development and various contamination events including wars and related oil spills. In this study, we used these three piscivorous top predator birds to analyse the levels of 19 trace elements (TEs; i.e. Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Pb, Sr, V and Zn) in 15 muscular tissue samples from Jana and Karan Islands. PERMANOVA analysis showed no difference in contamination profile between sites nor between species probably due to their spatial and ecological proximity and therefore similar levels of exposure to TEs. Comparing these levels with existing literature, our results showed no particular concern for all elements, except for Al (maximum values recorded = 116.5 µg g-1 d.w.) and, in two samples, Ba (33.67 µg g-1 d.w.) and Pb (5.6 µg g-1 d.w.). The results can be considered as an initial step for supplementary evaluations with a larger number of samples and specified time intervals for the collection of specimens. This study provided baseline information on the pollution status of these two ecologically important sites which require a continuous biomonitoring programme.

Exploration of the Pathogenesis of Chronic Obstructive Pulmonary Disease Caused by Smoking-Based on Bioinformatics Analysis and In Vitro Experimental Evidence.

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking-based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-ß signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.

Coral reefs in the northeastern Saudi Arabian Red Sea are resilient to mass coral mortality events.

We conducted an integrated survey combining visual census and baited remote underwater video survey on the coral reefs in the northeastern Red Sea and examined their health by comparing the baseline information from two decades ago. The mean coverage of the corals of all stations was 36 %, including 32 % stony corals and 4.0 % soft corals, significantly higher and lower to previous baseline. Observed high proportion of dead corals indicated the occurrence of the events of mass mortality, and the heating events were the most likely cause. Similar levels of coral coverage compared to two decades ago indicated their resilience to past events with mass coral mortality. Small proportions of macroalgae and sea urchins indicated that they might be controlled by their predators frequently observed in both visual census and underwater video survey. Regular monitoring and careful development plans are needed to safeguard these invaluable reefs.

Preliminary Study on the Effect and Molecular Mechanism of Tetrandrine in Alleviating Pulmonary Inflammation and Fibrosis Induced by Silicon Dioxide.

This study aims to explore the molecular mechanism of tetrandrine (Tet) in alleviating pulmonary inflammation and fibrosis induced by silica (SiO2) from the perspective of autophagy. C57BL/6J mice were selected as experimental animals, and SiO2 was exposed by intranasal instillation. Tet was intervened by oral gavage. The mice were euthanized on the 7th and 42nd day of SiO2 exposure, and lung tissues were collected for histopathological, molecular biological, immunological, and transmission electron microscopy analysis. The results showed that SiO2 exposure could lead to significant lung inflammation and fibrosis, while Tet could significantly reduce SiO2 exposure-induced lung inflammation and fibrosis. Molecular mechanism research indicated that, compared with SiO2 expose group, Tet intervention could significantly reduce the expression levels of inflammatory cytokines and fibrosis markers (TNF-α, IL-1ß, MCP-1, TGF-ß1, HYP, Col-I, and Fn), and regulate the expression of key molecules ATG7, microtubule-associated protein 1 light chain 3B (LC3B), and P62 in the autophagy pathway to improve the blocking of autophagic flux, promote the recovery of autophagic lysosomal system function, and inhibit apoptosis. In summary, Tet can alleviate silica-induced lung inflammation and fibrosis, which may be achieved by regulating the expression of key molecules in the autophagy process and associated apoptotic pathway.

Bioaccumulation of trace elements and hydrocarbons in chondrichthyans of the western Arabian Gulf: Environmental and human health risk assessment and implications for conservation.

This is a first attempt to assess the levels of trace elements, PAHs, and TPHs in six elasmobranch species (Carcharhinus dussumieri, C. sorrah, Chiloscyllium arabicum, Gymnura poecilura, Sphyrna lewini, S. mokarran) from the Arabian Gulf. The chemical analysis showed that the concentrations of contaminants differed significantly between liver and muscle samples with both pelagic and benthic species and all families. For all species, contaminant concentrations were significantly higher in the liver than in the muscle. While muscle contaminant concentrations differed significantly with respect to species' lifestyles and families, those of liver showed no significant differences between pelagic and benthic species, neither between the four families nor between the six species. None of the analysed contaminants exceeded the internationally recognized standards in all studied species. These results enrich the knowledge on the bioaccumulation of contaminants in elasmobranchs and allow to assess the environmental status of the Arabian Gulf.

Preliminary study on the role of aryl hydrocarbon receptor in the neurotoxicity of three typical bisphenol compounds (BPA, BPS and TBBPA) at environmentally relevant concentrations to adult zebrafish (Danio rerio).

Objective: This study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses. Methods: The adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 µmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 µmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out. Results: Compared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms. Conclusion: Environmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

Hsa-miR-379 down-regulates Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction by targeting connective tissue growth factor in human alveolar basal epithelial A549 cells.

OBJECTIVE: This study was aimed to screen and identify miRNAs that could regulate human CTGF gene and downstream cascade reaction Rac1/MLK3/JNK/AP-1/Collagen I by bioinformatics and experimental means. METHODS: TargetScan and Tarbase were used to predict miRNAs that may have regulatory effects on human CTGF gene. The dual-luciferase reporter gene assay was employed to verify the results obtained in bioinformatics. Human alveolar basal epithelial A549 cells were exposed to silica (SiO2) culture medium for 24 h to establish an in vitro model of pulmonary fibrosis, and bleomycin (BLM) of 100 ng/mL was used as a positive control. The miRNA and mRNA expression levels were determined by RT-qPCR, and the protein levels were measured by western blot in hsa-miR-379-3p overexpression group or not. RESULTS: A total of 9 differentially expressed miRNAs that might regulate the human CTGF gene were predicted. Hsa-miR-379-3p and hsa-miR-411-3p were selected for the subsequent experiments. The results of the dual-luciferase reporter assay showed that hsa-miR-379-3p could bind to CTGF, but hsa-miR-411-3p could not. Compared with the control group, SiO2 exposure (25 and 50 µg/mL) could significantly reduce the expression level of hsa-miR-379-3p in A549 cells. SiO2 exposure (50 µg/mL) could significantly increase the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM in A549 cells, while CDH1 level was significantly decreased. Compared with SiO2 + NC group, the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM were significantly decreased, and CDH1 level was significantly higher when hsa-miR-379-3p was overexpressed. At the same time, overexpression of hsa-miR-379-3p improved the protein levels of CTGF, Collagen I, c-Jun and phospho-c-Jun, JNK1 and phospho-JNK1 significantly compared with SiO2 + NC group. CONCLUSION: Hsa-miR-379-3p was demonstrated for the first time that could directly target and down-regulate human CTGF gene, and further affect the expression levels of key genes and proteins in Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction.

Rapid Identification and Analysis of Ochratoxin-A in Food and Agricultural Soil Samples Using a Novel Semi-Automated In-Syringe Based Fast Mycotoxin Extraction (FaMEx) Technique Coupled with UHPLC-MS/MS.

In this work, a fast mycotoxin extraction (FaMEx) technique was developed for the rapid identification and quantification of carcinogenic ochratoxin-A (OTA) in food (coffee and tea) and agricultural soil samples using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. The FaMEx technique advancement is based on two plastic syringes integrated setup for rapid extraction and its subsequent controlled clean-up process. In the extraction process, a 0.25-g sample and extraction solvent were added to the first syringe barrel for the vortex-based extraction. Then, the extraction syringe was connected to a clean-up syringe (pre-packed with C18, activated carbon, and MgSO4) with a syringe filter. Afterward, the whole set-up was placed in an automated programmable mechanical set-up for controlled elution. To enhance FaMEx technology performance, the various influencing sample pretreatment parameters were optimized. Furthermore, the developed FaMEx method indicated excellent linearity (0.9998 and 0.9996 for coffee/tea and soil) with highly sensitive detection (0.30 and 0.29 ng/mL for coffee/tea and soil) and quantification limits (1.0 and 0.96 for coffee/tea and soil), which is lower than the toxicity limit compliant with the European Union regulation for OTA (5 ng/g). The method showed acceptable relative recovery (84.48 to 100.59%) with <7.34% of relative standard deviation for evaluated real samples, and the matrix effects were calculated as <-13.77% for coffee/tea and -9.7 for soil samples. The obtained results revealed that the developed semi-automated FaMEx/UHPLC-MS/MS technique is easy, fast, low-cost, sensitive, and precise for mycotoxin detection in food and environmental samples.

Terminally ill patients' and their relatives' experiences and behaviors regarding complementary and alternative medicine utilization in hospice palliative inpatient care units: a cross-sectional, multicenter survey.

BACKGROUND: Terminally ill patients often experience exacerbations of diseases that render mainstream medicine ineffective in relieving symptoms, prompting attempts at complementary and alternative medicine (CAM). This study collected data from terminally ill patients and their relatives to determine differences between CAM use, behavioral patterns, and perceptions of health information about CAM. METHODS: A cross-sectional design using a self-administered questionnaire was adopted. Eight medical institutions in Taiwan with inpatient hospice palliative care units were chosen. Ninety-two terminally ill patients and 267 relatives met the inclusion criteria. The questions concerned the experience of CAM use, the kinds of products/services CAM provided, the purpose of CAM use, the source of CAM information, and the perceptions and attitudes toward CAM. RESULTS: Both terminally ill patients and their relatives have a high proportion of lifetime and one-year prevalence of CAM use (88.0% vs. 88.4%; p = 0.929). CAM use for musculoskeletal and neurological discomfort is higher among terminally ill patients than among their relatives. Relatives/friends are the most frequent sources of information on CAM (53.3% vs. 62.2%; p = 0.133). The percentage of terminally ill patients who discontinued mainstream medical treatment because of CAM use was higher than that of their relatives (18.5% vs. 9.3%; p = 0.026). More than half the terminally ill patients and their relatives had never been asked about CAM by medical staff (64.1% vs. 66.7%), nor had they informed medical professionals about the use of CAM products and services (63% vs. 66.9%). Random inquiries by medical professionals may be associated with increased disclosure of CAM use (terminally ill patients: odds ratio, 9.75; 95% confidence interval, 1.97-48.35 vs. relatives: odds ratio, 5.61; 95% confidence interval, 2.66-11.83). CONCLUSIONS: The high prevalence and concealment of CAM use in terminally ill patients should be considered. Medical professionals should establish a friendly and barrier-free communication model, encourage patients to share CAM experiences, and provide evidence-based information on the use of CAM products and services, to reduce the potential damage caused by harmful use.

Directional asymmetry in gonad length indicates moray eels (Teleostei, Anguilliformes, Muraenidae) are "right-gonadal".

Directional asymmetry indicates a unidirectional deviation from perfect bilateral symmetry, which was rarely examined in the inner organs of the teleost (Teleostei) compared to external traits. This study examines the directional asymmetry in the gonad length of 20 species of moray eels (Muraenidae) and two outgroup species with 2959 individuals. We tested three hypotheses: (1) moray eel species did not exhibit directional asymmetry in the gonad length; (2) the directional asymmetry pattern was the same for all selected species; (3) the directional asymmetry was not related to the major habitat types, depth and size classes, and taxonomic closeness of the species. Moray eels were generally "right-gonadal", the right gonad length being constantly and significantly longer than the left one in all studied Muraenidae species. The degree of asymmetry varied among species and was not significantly related to taxonomic closeness. The habitat types, depth, and size classes had intermingled effects on observed asymmetry without a clear correspondence. The directional asymmetry in the gonad length is a unique and widely occurring phenomenon in the Family Muraenidae, which was likely a by-product in the evolutionary history without significant disadvantage in survival.

Tracing Foodborne Botulism Events Caused by Clostridium botulinum in Xinjiang Province, China, Using a Core Genome Sequence Typing Scheme.

Foodborne botulism is a rare but life-threatening illness resulting from the action of a potent toxin mainly produced by Clostridium botulinum. It grows in an oxygen-deficient environment and is extremely viable in meat and soy products, making it one of the most virulent bacteria. How to track foodborne botulism events quickly and accurately has become a key issue. Here, we investigated two foodborne botulism events that occurred in Xinjiang in 2019 based on whole-genome sequencing and also successfully traced the relationship between clinical and food C. botulinum isolates using whole-genome core gene markers. All 59 isolates were classified as group I strains. Of the strains isolated in this study, 44 were found to be botulinum toxin A(B), and 15 isolates contained only the toxin B locus. Both the toxin A and B gene segments were located on the chromosome and organized in an ha cluster. Antibiotic resistance and virulence factors were also investigated. A set of 329 universal core gene markers were established using C. botulinum strains from a public database. These core gene markers were applied to the published C. botulinum genomes, and three outbreaks were identified. This work demonstrates that universal core gene markers can be used to trace foodborne botulism events, and we hope that our work will facilitate this effort in future. IMPORTANCE In this study, we analyzed 59 foodborne botulism (FB)-related strains isolated in Xinjiang Province, China. Our findings not only reveal the group classification, neurotoxin locus organization, antibiotic resistance and virulence factors of these strains but also establish a set of core gene markers for tracing foodborne botulism events, which was verified using published genomes. These findings indicate that these gene markers might be used as a potential tracing tool for FB events caused by C. botulinum group I strains, which have relatively stable genomic components.

Low Complement Factor H-Related 3 (CFHR3) Expression Indicates Poor Prognosis and Immune Regulation in Cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a cancerous tumor that leads to a high rate of morbidity and death. Complement factor H-related 3 (CFHR3) is a gene belonging to the CFHR gene family. In this study, we investigated the usefulness of CFHR3 in the diagnostic stage and CCA prognosis prediction. In the interim, we looked at its coexpressed genes and their roles. The correlation between CFHR3 and immunological infiltration was also investigated. Methods: The expression of the genes data and the clinical information were obtained from the databases of The Cancer Genome Atlas (TCGA) together with the Gene Expression Omnibus (GEO). The crucial gene was found to be the overlapping gene in the two databases. The area under the curve (AUC) and the Kaplan-Meier survival curve were used to describe the usefulness of the predictive prognosis of CCA patients. Univariate regression analysis and multivariate survival analysis were performed to find the independent prognosis factors. The PPI network was constructed based on the STRING database, and the coexpression approach was utilized in predicting the coexpression genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed to identify the related functions. Additionally, the probable mechanism of the important gene was examined using gene set enrichment analysis (GSEA). The correlation between CFHR3 and immune infiltration was discovered using TIMER. The LncACTdb 3.0 database was used to analyze the location of CFHR3 in the cell. The cBioPortal database was used to find the mutation in CFHR3. Results: TCGA datasets and GEO datasets revealed an elevated expression level of CFHR3 in normal tissues as well as a lower expression level in cholangiocarcinoma tissues in the present research. The low expression level of CFHR3 was related to an unfavorable prognosis. Using CFHR3 expression in diagnosis and predicting the patient prognosis (AUC = 1.000) is valuable. Using the CFHR3 gene and a time-lapse prediction, we could estimate survival rates over 1, 2, and 3 years. The AUC values were more than 0.6(AUC = 0.808; 0.760; 0.711). Functional enrichment analysis revealed a substantial correlation between this signature and complement and coagulation cascades. The same outcomes from GSEA were achieved. We found the key gene widely exists in the nucleus, exosomes, and cytoplasm of normal cells using the LncACTdb 3.0 database. In immune regulation analysis, we identified that the expression level of CFHR3 had a positive correlation with infiltrating levels of B cells, neutrophils, and macrophages, but correlated negatively with cholangiocarcinoma cells, CD8+ T cells, and monocytes.

[Using Creative Thinking Teaching to Improve Abdominal Drainage Tube Care Integrity Among Two-Year Post Graduate Nurses (PGNs)].

BACKGROUND & PROBLEMS: The abdominal drainage tube is an important device used in disease treatment and life maintenance. Drainage tube slippage leads to complications that increase both length of stay and costs of care. Four and seven cases of drainage tube slippage were reported, respectively, in 2018 and 2019 in our trauma wards. Among these, 9 cases were under the care of nurses in their post graduate year (PGY) training program. PURPOSE: To increase to 94% the abdominal drainage tube care-completeness rate of nurses in the PGY program. METHODS: Methods used included: establishing a standardized care module for abdominal drainage tube in the trauma wards, using the "drainage tube model" and multimedia teaching material in education to enhance skill proficiency, flexibly adjusting education schedules, using a creative-thinking teaching model in education, employing direct observation to evaluate PGY nurses' abdominal drainage tube skills; and establishing a drainage tube skill proficiency audit mechanism. RESULTS: After the intervention, the rate of care completeness for the abdominal drainage tube rose to 98.1%, participant awareness rose to 100%, and the rate of abdominal drainage tube slippage reduced to 0%. CONCLUSIONS: This project achieved good outcomes that may be expanded horizontally to other surgical wards. The use of the creative-thinking teaching model in training activities received good feedback from the nurse participants and will be incorporated into in-service education standards along with the computerized direct observation of procedural skills in the PGY e-learning passport to strengthen the completeness of learning processes.

Lymph-derived chemokines direct early neutrophil infiltration in the lymph nodes upon Staphylococcus aureus skin infection.

A large number of neutrophils infiltrate the lymph node (LN) within 4 h after Staphylococcus aureus skin infection (4 h postinfection [hpi]) and prevent systemic S. aureus dissemination. It is not clear how infection in the skin can remotely and effectively recruit neutrophils to the LN. Here, we found that lymphatic vessel occlusion substantially reduced neutrophil recruitment to the LN. Lymphatic vessels effectively transported bacteria and proinflammatory chemokines (i.e., Chemokine [C-X-C motif] motif 1 [CXCL1] and CXCL2) to the LN. However, in the absence of lymph flow, S. aureus alone in the LN was insufficient to recruit neutrophils to the LN at 4 hpi. Instead, lymph flow facilitated the earliest neutrophil recruitment to the LN by delivering chemokines (i.e., CXCL1, CXCL2) from the site of infection. Lymphatic dysfunction is often found during inflammation. During oxazolone (OX)-induced skin inflammation, CXCL1/2 in the LN was reduced after infection. The interrupted LN conduits further disrupted the flow of lymph and impeded its communication with high endothelial venules (HEVs), resulting in impaired neutrophil migration. The impaired neutrophil interaction with bacteria contributed to persistent infection in the LN. Our studies showed that both the flow of lymph from lymphatic vessels to the LN and the distribution of lymph in the LN are critical to ensure optimal neutrophil migration and timely innate immune protection in S. aureus infection.

Seasonal patterns of microplastics in surface sediments of a Mediterranean lagoon heavily impacted by human activities (Bizerte lagoon, Northern Tunisia).

In this paper, we investigated seasonal variations in concentrations of microplastics (MPs) in surface sediments of a lagoon heavily impacted by human activities, located in northern Tunisia (the Bizerte lagoon, southern Mediterranean Sea). Analyses of 112 sediment samples collected from 28 stations between May 2019 and February 2020 revealed significant seasonal variation in concentrations of total MPs, with the highest levels recorded in August 2019 (109.6 ± 59.8 items kg-1 DS (dry sediment)) and the lowest in February 2020 (33.2 ± 22.0 items kg-1 DS). In terms of polymer types, polyethylene particles were the most abundant throughout the year, followed by polypropylene, polyvinyl chloride, and polyethylene terephthalate. Spatial variations in total MP concentrations were found to depend on several environmental factors, including proximity to the coastline, level of anthropogenic pressure, location inside the lagoon, and presence/absence of vegetation. The upper 5-cm surface sediment layer of the lagoon was found to contain ~ 9.96 × 1010 MP particles, equal to ~ 248.97 t of plastic. Similar patterns of microplastic composition and structure were found throughout the year, revealing the same plastic pollution hotspots during all seasons. This indicates that sources of plastic pollution are land-based and originate from coastal urban, industrial, and agricultural areas, as well as from major freshwater streams. The findings of the present work can help to develop an efficient environmental management plan aiming to reduce and/or stop the spread of plastic pollution and its impacts on the socially and economically important ecosystem of the Bizerte lagoon.

Tumor-Draining Lymph Node Reconstruction Promotes B Cell Activation During E0771 Mouse Breast Cancer Growth.

Lymph node metastasis is associated with tumor aggressiveness and poor prognosis in patients. Despite its significance in cancer progression, how immune cells in the tumor-draining lymph node (TDLN) participate in cancer immune regulation remains poorly understood. It has been reported that both anti-tumor and exhausted tumor-specific T cells can be induced in the TDLNs; however, B cell activation and maturation in the TDLN has received far less attention. In our studies using C57BL/6 mouse syngeneic E0771 breast cancer or B16F10 melanoma cell lines, tumor-associated antigens were found colocalized with the follicular dendritic cells (FDCs) in the germinal centers (GCs), where antigen-specific B cell maturation occurs. LN conduits and the subcapsular sinus (SCS) macrophages are two major routes of antigen trafficking to FDCs. Tumor growth induced LN conduit expansion in the B cell zone and disrupted the SCS macrophage layer, facilitating both the entry of tumor-associated antigens into the B cell zone and access to FDCs located in the GCs. Regional delivery of clodronate liposome specifically depleted SCS macrophages in the TDLN, increasing GC formation, and promoting tumor growth. Our study suggests that TDLN reconstruction creates a niche that favors B cell activation and maturation during tumor growth.

Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway.

Bradykinin (BK) is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects. We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation (ROSC) after cardiac arrest. However, the precise mechanism underlying this process remains poorly understood. In this study, we treated a rat model of ROSC after cardiac arrest (induced by asphyxiation) with 150 µg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest. We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest, increased the amount of autophagosomes in the hippocampal tissue, inhibited neuronal cell apoptosis, up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62, inhibited the expression of the brain injury marker S100ß and apoptosis-related protein caspase-3, and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins. Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest, which aggravated the injury caused by ROSC. The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy. Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

[Neuroprotective mechanism of autophagy in bradykinin postconditioning after cardiac arrest in rats].

OBJECTIVE: To explore the protective effects of bradykinin postconditioning on cardiopulmonary resuscitation (CPR) rats, and to assess the underlying mechanisms. METHODS: Forty-eight adult male Sprague-Dawley (SD) rats were randomly divided into four groups according to random number table: Sham operation group, cardiac arrest (CA) group, bradykinin treatment (BK) group, and AMP-activated protein kinase (AMPK) inhibitor Compound C+ bradykinin treatment (CP+BK) group, finally, 8 rats in each group were taken for follow-up experiment. CA was induced by asphyxia. Rats in the Sham group received arteriovenous catheterization, endotracheal intubation, and mechanical ventilation, without CA. Compound C (250 µg/kg) was intraperitoneally injected in CP+BK group 30 minutes before CA, and the same volume of dimethyl sulfoxide (DMSO) was given in the remaining groups. Bradykinin (150 µg/kg) was intraperitoneally injected in BK group and CP+BK group 48 hours after restoration of spontaneous circulation (ROSC), and same volume of saline was given in the remaining groups. The neural function of rats in each group was evaluated with neurological deficit score (NDS) 72 hours after ROSC. Microtubule-associated protein light chain 3 (LC3) and p62 expressions were detected by immunohistochemistry, autophagosomes were observed by transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL) assay was used to assess apoptosis. RESULTS: Compared with the Sham group, the NDS was decreased (60.75±5.80 vs. 80.00±0.00, P < 0.01), the expression levels of LC3 and p62 elevated [LC3 (A value): 1.04±0.64 vs. 0.40±0.14, p62 (A value): 2.75±0.57 vs. 0.36±0.12, both P < 0.05], the number of autophagosomes and apoptotic cells increased in the CA group [(39.00±8.00)% vs. (3.87±1.90)%, P < 0.05]. Compared with the CA group, the NDS (67.75±6.32 vs. 60.75±5.80, P < 0.05), the expression of LC3 (A value: 1.60±0.34 vs. 1.04±0.64, P < 0.05), and the number of autophagosomes increased in the BK group, while the expression of p62 and the rate of apoptotic cells reduced [p62 (A value): 1.51±0.32 vs. 2.75±0.57, apoptotic cells rate: (23.03±1.91)% vs. (39.00±8.00)%, both P < 0.05]. Compared with the BK group, the NDS (59.00±8.19 vs. 67.75±6.32, P < 0.05), the expression of LC3 (A value: 0.62±0.41 vs. 1.60±0.34, P < 0.05) and the number of autophagosomes declined in the CP+BK group, while the expression of p62 and the rate of apoptotic cells elevated [p62 (A value): 3.50±0.47 vs. 1.51±0.32, apoptotic cells rate: (44.53±10.15)% vs. (23.03±1.91)%, both P < 0.05]. CONCLUSIONS: Bradykinin postconditioning played a neuroprotective role in CPR rats by activating autophagy and reducing apoptosis.

Essential fish habitats of demersal fish in the western Arabian Gulf.

Information about habitats occupied by aquatic organisms while completing critical stages of their lives, called essential fish habitats, is crucial for their sustainability. In this work, we determine essential fish habitats (nursery and spawning grounds) of several fish species inhabiting Saudi territorial waters in the western Arabian Gulf using data from multiple surveys (2013-2016), geostatistics, and indicator species analysis. We built geostatistical maps of spatial distributions of juvenile and mature fish and examined the strength of association of each species to its observed nursery and spawning areas. Fish nursery areas were generally located in nearshore locations while spawning areas were located in offshore waters. The patterns of nursery and spawning grounds were highly varied among species, supporting a hypothesis of habitat-species heterogeneity: different species use different locations as nursery and spawning grounds. This information can be used as a roadmap for future evidence-based spatial planning and ecosystem-based management.