Immune and physiological responses of Mytilus unguiculatus to Alexandrium spp. with varying paralytic shellfish toxin profiles.

The innate immunity of bivalves serves as the initial defense mechanism against environmental pollutants, ultimately impacting genetic regulatory networks through synergistic interactions. Previous research has demonstrated variations in the accumulation and tolerance capacities of bivalves; however, the specific mechanism underlying the low accumulation of PSTs in M. unguiculatus remains unclear. This study examined the alterations in feeding behavior and transcriptional regulation of M. unguiculatus following exposure to two Alexandrium strains with distinct toxin profiles, specifically gonyautoxin (AM) and N-sulfocarbamoyl toxin (AC). The total accumulation rate of PSTs in M. unguiculatus was 43.64 % (AC) and 27.80 % (AM), with highest PSTs content in the AM group (455.39 µg STXeq/kg). There were significant variations (P < 0.05) in physiological parameters, such as total hemocyte count, antioxidant superoxide activity and tissue damage in both groups. The absorption rate was identified as the key factor influencing toxin accumulation. Transcriptomic analyses demonstrated that PSTs triggered upregulation of endocytosis, lysosome, and immune-related signaling pathways. Furthermore, PSTs induced a nucleotide imbalance in the AC group, with total PSTs content serving as the most toxic indicator. These results suggested that protein-like substances had a crucial role in the stress response of M. unguiculatus to PSTs. This study provided novel perspectives on the impacts of intricate regulatory mechanisms and varying immune responses to PSTs in bivalves.

Effects of perfluorooctanoic acid on the nutritional quality of Mytilus edulis.

Perfluorooctanoic acid (PFOA), which widely presents in marine environment, may produce some adverse effects to aquatic organism. Mytilus edulis are popular due to their high protein and low fat content in China. However, few studies have investigated the effects of PFOA on the quality of aquatic products. Here, PFOA effects on basic nutritional indices in M. edulis were measured, and possible mechanisms were explored. PFOA caused clear variation in physiological and biochemical indices of M. edulis. The contents of some important proteins, nutrients, and amino acids etc. dropped. Integrating metabolomics data, we speculate PFOA exposure triggered inflammation and oxidative stress in mussels, interfered with the metabolic pathways related to the quality and the transport and absorption pathways of metal ions, and affected the levels of some important elements and metabolites, thus decreasing the nutritional quality of M. edulis. The study provides new insights into PFOA adverse effects to marine organism, and may offer some references for some researchers to assess food quality and ecological risk to pollutants.

A novel ZIF-L/PEI thin film nanocomposite membrane for removing perfluoroalkyl substances (PFASs) from water: Enhanced retention and high flux.

Membrane separation technology is widely recognized as an effective method for removing perfluoroalkyl substances (PFASs) in water treatment. ZIF-L, a metal-organic framework (MOF) family characterized by its mat-like cavities and leaf-like morphology, has garnered considerable interest and has been extensively employed in fabricating thin-film nanocomposite (TFN) membranes. In this study, a robust, high-performance TFN membrane to remove PFASs in a nanofiltration (NF) process was created through an interfacial polymerization approach on the surface of polysulfone (PSF), incorporating ZIF-L within the selective layer. The TFN membrane modified by adding 5 wt% ZIF-L (relative to the weight of ethylene imine polymer (PEI)) exhibits 2.3 times higher water flux (up to 47.56 L·m-2·h-1·bar-1) than the pristine thin film composite membrane (20.46 L·m-2·h-1·bar-1), and the rejection for typical PFASs were above 95 % (98.47 % for perfluorooctanesulfonic acid (PFOS) and 95.85 % for perfluorooctanoic acid (PFOA)). The effectiveness of the ZIF-L/PEI TFN membrane in retaining representative PFASs was examined under various conditions, including different pressures, feed concentrations, aqueous environments, and salt ions. Notably, the experiments demonstrated that even after contamination with humic acid (HA), >88 % of the water flux could be restored by washing. Additionally, density functional theory (DFT) calculations were employed to predict the distinct intermolecular interactions between PFASs and ZIF-L as well as PEI. These calculations provide additional insights into the interception mechanism of TFN membranes towards PFASs. Based on this study, TFN membranes incorporating MOF as nanofillers show great potential as an effective method for purifying PFASs from aqueous environments and possess superior environmental sustainability and cost-effectiveness.

Influence of humic acid on the bioaccumulation, elimination, and toxicity of PFOS and TBBPA co-exposure in Mytilus unguiculatus Valenciennes.

Tetrabromobisphenol A (TBBPA) and Perfluorooctane sulfonate (PFOS) are emerging contaminants which coexist in marine environments, posing significant risks to ecosystems and human health. The behavior of these contaminants in the presence of dissolved organic matter (DOM), specifically the co-contamination of TBBPA and PFOS, is not well understood. The bioaccumulation, distribution, elimination, and toxic effects of TBBPA and PFOS on thick-shell mussels (Mytilus unguiculatus V.), with the absence and presence of humic acid (HA), a typical DOM, were studied. The results showed that the uptake of TBBPA decreased and the uptake of PFOS increased when exposed to 1 mg/L HA. However, at higher concentrations of HA (5 and 25 mg/L), the opposite effect was observed. Combined exposure to HA, TBBPA, and PFOS resulted in oxidative stress in the digestive gland, with the severity of stress dependent on exposure time and HA dose. Histological analysis revealed a positive correlation between HA concentration and tissue damage caused by TBBPA and PFOS. This study provides insights into the influence of HA on the bioaccumulation-elimination patterns and toxicity of TBBPA and PFOS in marine bivalves, offering valuable data for ecological and health risk assessments of combined pollutants in aquatic environments rich in DOM.

Integrated evidence of transcriptional, metabolic, and intestinal microbiota changes in Ruditapes philippinarum due to perfluorooctanoic acid-induced immunotoxicity.

Perfluorooctanoic acid (PFOA) is a toxic pollutant that bioaccumulates and is a significant public health concern due to its ubiquitous and persistent occurrence in global environments. Few studies have evaluated the adverse effects of PFOA on immune system, and this is particularly true for mollusks. Here, the PFOA-associated effects on immune system were evaluated in Ruditapes philippinarum using integrated analysis of metabolomes, microbiomes, and transcriptomes, providing evidence for possible mechanisms related to immunotoxicity. PFOA exposure caused clear variation in several important metabolites related to immune regulatory function within the haemolyph from R. philippinarum, while also altering key metabolic pathways, including those of lipids, unsaturated fatty acids (UFAs), and bile acids (BAs). After exposure to PFOAs, intestinal bacterial communities also clearly changed, with the predominant microflora becoming Mycoplasma and Bacteroidetes that are related to intestinal inflammation. Molecular analyses provided consistent results, wherein the expression of immune-related genes was significantly altered. Integration of the multi-'omics' analyses suggested that the TLR/MyD88/NF-kB pathway, along with PI3K-Akt-mTOR pathway, PPAR-mediated lipid metabolism and the autophagy signaling pathway, likely play important roles in initiating immunotoxic effects in R. philippinarum after PFOA exposure. These results provide further evidence that PFOA exposure can lead to immunologic dysfunction and also provide new insights into the mechanisms of PFAS alteration of bivalve immune function.

New insights into the oxidative damage and antioxidant defense mechanism in Manila clams (Ruditapes philippinarum) exposed to 8:2 polyfluoroalkyl phosphate diester stress.

8:2 perfluoroalkyl phosphate diester (8:2 diPAP) is the main precursor of perfluoroalkyl carboxylic acids, and it has been detected in a wide range of environments. In this study, conventional biochemical and histopathological analyses and transcriptome methods were used to investigate the accumulation and oxidative stress of 8:2 diPAP in Manila clams (Ruditapes philippinarum) as well as the clam's defense mechanisms for the first time. The hepatopancreas was the main target organ for 8:2 diPAP accumulation; the concentration reached 484.0 ±â€¯15.5 ng/g after 7 days of exposure to 10 µg/L of 8:2 diPAP, which was 2-100 times higher than that found in other organs. 8:2 diPAP accumulation resulted in significant lipid peroxidation, and the change in malondialdehyde content was highly correlated with 8:2 diPAP accumulation (r > 0.8). The antioxidant enzymes catalase and peroxidase were significantly activated at 7 days of exposure. Although the levels subsequently returned to normal, this restoration was unable to prevent damage. Histopathological analysis showed that 8:2 diPAP exposure resulted in inflammatory damage to the hepatopancreas, which failed to resolve during the recovery period. Transcriptomic analyses showed that the expression of differentially expressed genes had different degrees of positive/negative correlation with antioxidant indicators, and they were significantly enriched in cell death regulatory pathways such as autophagy, apoptosis, and necrosis. The core factor expression results indicated that 8:2 diPAP exposure induced activation of the organismal autophagy factor followed by a shift towards apoptosis. In addition, pathways related to amino acid metabolism and energy metabolism were involved in determining the cell fate of Manila clams. Overall, these results indicated that 8:2 diPAP induced peroxidation of membrane lipids, disturbed physiological processes, and ultimately initiated programmed cell death in Manila clams. The findings of this study provide new insights into the mechanism of toxicity of 8:2 diPAP exposure in marine bivalves.

CircSMARCA5 silencing impairs cell proliferation and invasion via the miR-17-3p-EGFR signaling in lung adenocarcinoma.

AIMS: Circular RNAs are widely expressed in various cancers and play important roles in tumorigenesis and tumor progression. The function and mechanism of circSMARCA5 in lung adenocarcinoma however remains unclear. MAIN METHODS: QRT-PCR analysis was applied for determining circSMARCA5 expression in lung adenocarcinoma patient tumor tissues and cells. Molecular biological assays were used for investigating the role of circSMARCA5 in lung adenocarcinoma progression. Luciferase reporter and bioinformatics assays were used for identifying the underlying mechanism. KEY FINDINGS: In this study, we observed that circSMARCA5 expression was decreased in lung adenocarcinoma tissues but silencing of circSMARCA5 in lung adenocarcinoma cells inhibited cell proliferation, colony formation, migration and invasion. Mechanistically, we found EGFR, c-MYC and p21 were down-regulated upon circSMARCA5 knockdown. MiR-17-3p efficiently down- regulated EGFR expression via directly binding to EGFR mRNA. SIGNIFICANCE: These studies suggest that circSMARCA5 functions as an oncogene via targeting miR-17-3p-EGFR axis and may represent a promising therapeutic target for lung adenocarcinoma.

Perfluoroalkyl substances (PFASs) in aquatic products from the Yellow-Bohai Sea coasts, China: Concentrations and profiles across species and regions.

Perfluoroalkyl substances (PFASs) are emerging contaminants capable of harming human health, primarily via ingesting aquatic products. The current study monitored a survey of 23 PFASs in 1049 aquatic products from the coasts of the Yellow-Bohai Sea in China to comprehensively investigate the concentrations and distributions of PFASs. PFOA, PFOS, PFNA, PFOSA, and PFUdA were more predominantly and frequently detected than other PFASs in all samples, dominating PFAS patterns in aquatic products. The mean levels of ∑PFASs in different species followed the order: marine shellfish > marine crustaceans > fish > cephalopods > sea cucumber. Profiles of PFASs differ between species, suggesting species-specific accumulation plays a role. Various aquatic species are potential environmental bioindicators that signal individual PFAS contamination. For instance, clams can act as a potential PFOA bioindicator. High ∑PFAS levels in some sites (such as Binzhou, Dongying, Cangzhou, and Weifang) could be attributed to industrial activities involving fluoropolymer manufacture. The differences between PFAS concentrations and profiles in aquatic products across the study regions have been proposed as PFAS fingerprints of the Yellow-Bohai Sea coasts. Analyses of principal components and Spearman correlations indicated that the precursor biodegradation possibly contribute to C8-C10 PFCAs in the study samples. This study reported a wide presence of PFASs in different species of aquatic products across the Yellow-Bohai Sea coasts. The potential health risks that PFASs pose in certain species (such as marine shellfish and marine crustaceans) should not be neglected.

Monitoring and analysis of desertification surrounding Qinghai Lake (China) using remote sensing big data.

Desertification is one of the most serious ecological environmental problems in the world. Monitoring the spatiotemporal dynamics of desertification is crucial for its control. The region around Qinghai Lake, in the northeastern part of the Qinghai-Tibet Plateau in China, is a special ecological function area and a climate change sensitive area, making its environmental conditions a great concern. Using cloud computing via Google Earth Engine (GEE), we collected Landsat 5 TM, Landsat 8 OLI/TIRS, and MODIS Albedo images from 2000 to 2020 in the region around Qinghai Lake, acquired land surface albedo (Albedo), and normalized vegetation index (NDVI) to build a remote sensing monitoring model of desertification. Our results showed that the desertification difference index based on the Albedo-NDVI feature space could reflect the degree of desertification in the region around Qinghai Lake. GEE offers significant advantages, such as massive data processing and long-term dynamic monitoring. The desertification land area fluctuated downward in the study area from 2000 to 2020, and the overall desertification status improved. Natural factors, such as climate change from warm-dry to warm-wet and decreased wind speed, and human factors improved the desertification situation. The findings indicate that desertification in the region around Qinghai Lake has been effectively controlled, and the overall desertification trend is improving.

Characteristic Profile of the Hazardous, Nutritional, and Taste-Contributing Compounds during the Growth of Argopecten irradians with Different Shell Colors.

Bay scallops (Argopecten irradians; A. irradians) are shellfish with high nutritional and economic value. However, nutritional studies on A. irradians with different shell colors are limited. This study examines the hazardous, nutritional, and taste-contributing compounds during the growth of A. irradians with different shell colors. During the growth of A. irradians, the hazardous contents were below the standard limit. Changes in the nutritional and taste-contributing compounds between months were more significant than shell color. Bay scallops had more fats, total fatty acids, and taste-contributing compounds in August and more proteins, essential fatty acids, vitamin D, vitamin B12, Cu, and Zn in September and October. In October, the golden shell color strain had more proteins, essential fatty acids, vitamin D, vitamin B12, Cu, and Zn, while the purple shell color strain had more taste-contributing compounds. A. irradians had better taste in August and higher nutritional value in September and October. In October, the golden shell color strain has higher nutritional value, and the purple shell color strain has better commercial value and taste. The correlation analysis indicates that the nutritional quality of bay scallops is affected by age (months), shell color, and seawater environment.

A Dual-Channel Microfluidic Chip for Single Tobacco Protoplast Isolation and Dynamic Capture.

Protoplasts are widely used in gene function verification, subcellular localization, and single-cell sequencing because of their complete physiological activities. The traditional methods based on tissues and organs cannot satisfy the requirement. Therefore, the isolation and capture of a single protoplast are most important to these studies. In this study, a dual-channel microfluidic chip based on PDMS with multi-capture cavities was designed. The design theory of the dual-channel microfluidic chip's geometry was discussed. The capture mechanism of the single cell in a dual-channel microfluidic chip was studied by simulation analysis. Our results showed that a single polystyrene microsphere or tobacco protoplast was successfully isolated and trapped in this chip. The capture efficiency of the chip was 83.33% for the single tobacco protoplast when the inlet flow rate was 0.75 µL/min. In addition, the dynamic capture of the polystyrene microsphere and tobacco protoplasts was also presented. Overall, our study not only provided a new strategy for the subsequent high throughput single protoplast research, but also laid a theoretical foundation for the capture mechanism of the single cell.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

Deactivation of AKT/GSK-3ß-mediated Wnt/ß-catenin pathway by silencing of KIF26B weakens the malignant behaviors of non-small cell lung cancer.

Kinesin family member 26B (KIF26B) is reported differently expressed in multiple neoplasms and exerts a pivotal role in carcinogenesis. To date, the relationship between KIF26B and non-small cell lung cancer (NSCLC) is unaddressed. This study explored the possible roles and mechanisms of KIF26B in NSCLC. We observed high levels of KIF26B in NSCLC, and demonstrated that high KIF26B levels predicted an overall shorter duration of survival. Functional experiments demonstrated that restraint of KIF26B by gene knockdown exhibited remarkable tumor-suppressive effects in NSCLC in vitro, including repression of cell proliferation, induction of G0/G1 cell cycle arrest, suppression of cell invasion and epithelial-mesenchymal transition, and enhancement of chemotherapeutic sensitivity. The study further revealed that inhibition of KIF26B was able to affect the activation of ß-catenin via regulation of the AKT/GSK-3ß axis. Moreover, forced expression of ß-catenin could reverse KIF26B-silencing-evoked tumor-suppressive effects. Importantly, NSCLC cells with KIF26B silencing exhibited decreased growth potential in nude mice in vivo. Collectively, our data indicate that restraint of KIF26B has a tumor-suppressive role in NSCLC by affecting the AKT/GSK-3ß/ß-catenin pathway. This work unveils a pivotal role of KIF26B in NSCLC and suggests it as a viable target for anti-NSCLC therapy.

Effects of single and combined exposure to BDE-47 and PFOA on distribution, bioaccumulation, and toxicity in blue mussel (Mytilus galloprovincialis).

The contamination of 2,2',4,4'-Tetrabrmodiphenyl ether (BDE-47) and perfluorooctanoic acid (PFOA) has drawn a worldwide attention over the risks in ecological and food safety. In this work, blue mussel (Mytilus galloprpvincialis) was employed to investigate the combined effects of BDE-47 (10 ng mL-1) and PFOA (100 ng mL-1) on tissue distribution, accumulation, elimination, and toxicity. Results suggested that BDE-47 and PFOA accumulated mostly in digestive gland, followed by gills and gonad, and M. galloprovincialis displayed higher accumulation capacity to BDE-47 than PFOA. Co-exposure treatment reduced the accumulation of BDE-47, and enhanced the accumulation of PFOA. Furthermore, biochemical and histopathological tests revealed that the aggravated toxicity in co-exposure groups was mainly attributed to the oxidative stress and damage of tissue structure. This work could be helpful to get a better understanding of the combined behaviors and cumulative risks of BDE-47 and PFOA in marine ecosystem.

[Effects of long-term nitrogen addition on the nitrogen pools in a meadow steppe ecosystem]. / é•¿æœŸæ°®æ·»åŠ å¯¹è‰ç”¸è‰åŽŸç”Ÿæ€ç³»ç»Ÿæ°®åº“çš„å½±å“.

Increasing atmospheric nitrogen (N) deposition greatly affects species diversity, productivity, and stability of ecosystems. It is thus of the great importance to understand how grassland N pools respond to the increased atmospheric N deposition. This study was conducted in a meadow steppe in Erguna, Inner Mongolia, China. There were six levels of N addition (i.e., 0, 2, 5, 10, 20 and 50 g·m-2·a-1) and two levels of mowing (i.e., mowing and unmown). Samples of aboveground tissues of dominant plant, root, aboveground litter, and soil to the depth of 100 cm were collected in the seventh year after treatments. The N content was measured and the N pool was calculated. The results showed that N addition significantly increased the N content of aboveground plant tissues and litter, as well as N pools of Leymus chinensis, plant community, litter and ecosystem. Mowing significantly increased the N content of L. chinensis leaf and litter, but reduced N pools of L. chinensis, plant community and litter, and did not affect their responses to N addition. There was a significant interactive effect between mowing and N addition on plant community N pool. High levels of N addition in the unmown treatment led to more N stored in the litter pool, with the saturation threshold for the plant community N pool occurred at 10 g·m-2·a-1. Under mowing treatment, the plant community N pool increased with the increasing N addition, and more N stored in plant community N pool after mowing. Mowing could alleviate the negative impacts of increasing N deposition on biodiversity and ecosystem stability, and extended postponing the occurrence of ecosystem N saturation induced by increasing N deposition.

Uptake, Tissue Distribution, and Elimination of 8:2 Polyfluoroalkyl Phosphate Diesters in Mytilus galloprovincialis.

Although the distribution of 8:2 polyfluoroalkyl phosphate diester (8:2 diPAP) in aquatic environments has been reported, details on its uptake, tissue specificity, and elimination in bivalve mollusks remain to be clarified. The present study is the first report on the accumulation and elimination of 8:2 diPAP in mussels (Mytilus galloprovincialis). The tissue-specific accumulation and depuration of 8:2 diPAP and its metabolites were investigated via semistatic seawater exposure (8:2 diPAP at a nominal concentration of 10 µg/L), through water-borne exposure with static daily renewal over a 72-h exposure period and a 360-h depuration period. The digestive gland was found to be the target organ where accumulation and biotransformation primarily occur. The bioaccumulation factor values (mL/g dry wt) in different organs were in the following order: digestive gland (1249) > adductor muscle (315) > gills (289) > gonad (82.9) > mantle (33.0). Moreover, the distribution of 8:2 diPAP among tissues may be related to the total protein content. The 8:2 diPAP tended to be excreted in feces. The compounds 8:2 fluorotelomer carboxylic acid, 8:2 fluorotelomer unsaturated carboxylic acid, 7:3 fluorotelomer carboxylic acid, perfluorooctanoic acid, and perfluoroheptanoic acid were detected and quantified as phase I metabolites, and the concentration of all phase I metabolites relative to the 8:2 diPAP concentration (72 h) was 0.304 mol%. A phase II metabolite, 8:2 fluorotelomer alcohol conjugated with sulfate, was detected but not quantitated in the digestive gland. A biotransformation pathway of 8:2 diPAP in M. galloprovincialis was proposed on the basis of the results obtained in the present study and previous studies. These findings improve our understanding of the accumulation of perfluorocarboxylic acids in bivalve mollusks. Environ Toxicol Chem 2021;40:1992-2004. © 2021 SETAC.

LncRNA NORAD, sponging miR-363-3p, promotes invasion and EMT by upregulating PEAK1 and activating the ERK signaling pathway in NSCLC cells.

Lung cancer is one of the most common malignant tumors in the world. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. About 75% of patients are in the middle and advanced stages at the time of discovery, and the 5-year survival rate is very low. The aim of this study was to investigate the role of long non-coding RNA (lncRNA) NORAD in the pathogenesis of NSCLC. We found that lncRNA NORAD was highly expressed in human NSCLC tissues and cell lines. The CCK-8 assay results showed that lncRNA NORAD had no effect on cell proliferation. The Transwell assay and Western blotting results showed that overexpression of lncRNA NORAD promoted the invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells. Then bioinformatics analysis was used to screen for candidate miRNA bound with lncRNA NORAD and the target gene of miRNA in NSCLC. The luciferase reporter gene assay and RNA pull-down assay were used to verify the relationship. We found that miR-363-3p expression was down-regulated, whereas PEAK1 expression was upregulated in NSCLC cells. We performed gain and loss function test of lncRNA NORAD, miR-363-3p and PEAK1, the results showed that while miR-363-3p-mimic inhibited cell invasion and EMT by targeting PEAK1, lncRNA NORAD acted as a sponge of miR-363-3p and promoted cell invasion and EMT by increasing the expression of PEAK1. In addition, p-ERK expression was detected by Western blotting to observe the effects of lncRNA NORAD, miR-363-3p and PEAK1 on activation of the ERK signaling pathway. Taken together, lncRNA NORAD upregulated the expression of PEAK1 through sponging miR-363-3p, and then activated the ERK signaling pathway, thereby promoting the development of NSCLC.

Complex network dynamics of the topological structure in a geochemical field from the Nanling area in South China.

The topological classification of geochemical elements is widely used as a reference for regional prospecting prediction. In this study, we analyze the topological correlation structures of 39 representative geochemical elements from the Nanling area of South China by implementing the complex networks theory. The topological correlation structures of geochemical elements have a high clustering coefficient (0.8120-0.8880), but the magnitude of the shortest path (1.2950-2.3600) is small. In combination with the analysis of complex networks characteristics, we report that the topological correlation structures of the geochemical elements in this area have small-world characteristics, which reveals the self-organized criticality. As shown in the topological network, two random elements have some level of associations, which present a specific community feature. Our preliminary result shows that with changing the control parameter (k) of "coarse-graining", the topological correlation structures undergo two critical phase transitions. As the control parameter (k) reaches 0.44, the entire element system evolves into two parts. When the control parameter (k) reaches 0.63, the system forms three "communities". It is worth noting that the three "communities" are basically consistent with the Goldschmidt's geochemical classification of the elements, which are lithophile, siderophile, and chalcophile groups, respectively. In these "communities", we also found that a small level of component units is nested.

Schisandra chinensis bee pollen's chemical profiles and protective effect against H2O2-induced apoptosis in H9c2 cardiomyocytes.

BACKGROUND: Schisandra chinensis (Turcz.) Baill bee pollen extract (SCBPE) is often used as a functional food in China due to its good antioxidant property. However, its chemical compositions and effects on H9c2 cardiomyocytes against H2O2-induced cell injury still lacks of reports thus far. This study aimed to characterize the main components of SCBPE and investigate its protective effects against H2O2-induced H9c2 cardiomyocyte injury. METHODS: The main components of SCBPE were analyzed via ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF MS/MS). The three main nucleosides in SCBPE were quantitatively analyzed via ultraperformance liquid chromatography-diode array detection. Furthermore, the potential mechanism by which SCBPE exerts protective effects against H2O2-induced H9c2 cardiomyocyte injury was explored for the first time via cell survival rate measurements; cell morphological observation; myocardial superoxide dismutase (SOD) activity and malondialdehyde (MDA) and glutathione (GSH) level determination; flow cytometry; and quantitative polymerase chain reaction. RESULTS: Two carbohydrates, three nucleosides, and nine quinic acid nitrogen-containing derivatives in SCBPE were identified or tentatively characterized via UPLC-QTOF MS/MS. The nine quinic acid nitrogen-containing derivatives were first reported in bee pollen. The contents of uridine, guanosine, and adenosine were 2.4945 ± 0.0185, 0.1896 ± 0.0049, and 1.8418 ± 0.0157 µg/mg, respectively. Results of in vitro experiments showed that cell survival rate, myocardial SOD activity, and GSH level significantly increased and myocardial MDA level significantly decreased in SCBPE groups compared with those in H2O2 group. Cell morphology in SCBPE groups also markedly improved compared with that in H2O2 group. Results indicated that SCBPE protected H9c2 cardiomyocytes from H2O2-induced apoptosis by downregulating the mRNA expressions of Bax, cytochrome C, and caspase-3 and upregulating the Bcl-2 mRNA expression. CONCLUSIONS: This study is the first to report that SCBPE could protect against oxidative stress injury and apoptosis in H2O2-injured H9c2 cells. Results indicated that the nucleosides and quinic acid nitrogen-containing derivatives could be the main substances that exert protective effects against H2O2-induced H9c2 cardiomyocyte injury.