Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish.

Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39-2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT-PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects.

Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification.

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.

Comprehensive profiling of L1 retrotransposons in mouse.

L1 elements are retrotransposons currently active in mammals. Although L1s are typically silenced in most normal tissues, elevated L1 expression is associated with a variety of conditions, including cancer, aging, infertility and neurological disease. These associations have raised interest in the mapping of human endogenous de novo L1 insertions, and a variety of methods have been developed for this purpose. Adapting these methods to mouse genomes would allow us to monitor endogenous in vivo L1 activity in controlled, experimental conditions using mouse disease models. Here, we use a modified version of transposon insertion profiling, called nanoTIPseq, to selectively enrich young mouse L1s. By linking this amplification step with nanopore sequencing, we identified >95% annotated L1s from C57BL/6 genomic DNA using only 200 000 sequencing reads. In the process, we discovered 82 unannotated L1 insertions from a single C57BL/6 genome. Most of these unannotated L1s were near repetitive sequence and were not found with short-read TIPseq. We used nanoTIPseq on individual mouse breast cancer cells and were able to identify the annotated and unannotated L1s, as well as new insertions specific to individual cells, providing proof of principle for using nanoTIPseq to interrogate retrotransposition activity at the single-cell level in vivo.

Therapeutic potential of hydrogen sulfide in osteoarthritis development.

The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (H2S) in OA and the therapeutic potential of H2S donors. The review highlights the importance of changes in the endogenous H2S pathway in OA development and systematically elaborates on the role of H2S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H2S can lessen bone and joint inflammation by inhibiting leukocyte adhesion and migration, reducing pro-inflammatory mediators, and impeding the activation of key inflammatory pathways such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, H2S is shown to mitigate mitochondrial dysfunction and endoplasmic reticulum stress, and to modulate Nrf2, NF-κB, PI3K/Akt, and MAPK pathways, thereby decreasing oxidative stress-induced chondrocyte apoptosis. Moreover, H2S alleviates bone and joint pain through the activation of Kv7, K-ATP, and Nrf2/HO-1-NQO1 pathways. Recent developments have produced a variety of H2S donors, including sustained-release H2S donors, natural H2S donors, and synthetic H2S donors. Understanding the role of H2S in OA can lead to the discovery of new therapeutic targets, while innovative H2S donors offer promising new treatments for patients with OA.

Active compounds from Calendula officinalis flowers act via PI3K and ERK signaling pathways to offer neuroprotective effects against Parkinson's disease.

Calendula officinalis flowers, associated with diverse biological effects, could be utilized as functional food ingredients to play a crucial role in human health. In this study, we examined the anti-PD activity of C. officinalis flower extracts and investigated their bioactive compounds and molecular mechanisms based on LC-MS/MS assay, bioinformatic exploration and in vitro treatment of SH-SY5Y cells. C. officinalis extracts exhibited significant positive effects on the length and fluorescence density of the dopaminergic neuron region in zebrafish larvae. At 10 µg/mL, the extract restored the length to 96.54% and fluorescence density to 87.77% of the control values, which was equivalent to the effect of a positive drug, indicating the extract's powerful potential to alleviate PD symptoms. Five active compounds, including chlorogenic acid, 3,4-dicaffeoylquinic acid (DA), rutin, isorhamnetin 3-O-glucoside (IG) and calenduloside E (CE) were identified in extracts by LC-QTOF-MS/MS. Hsp90α, PI3K and ERK were revealed as core targets of DA, IG and CE in relation to anti-PD activity. The compounds docked deeply within the pocket region of Hsp90α protein, and their binding energies (∆G b) were -6.93 kcal/mol (DA), -6.51 kcal/mol (IG) and -3.03 kcal/mol (CE), respectively. Subsequently, they concurrently activated the PI3K/Akt signaling pathway and inhibited the ERK signaling pathway, thereby preventing neuronal death and alleviating neuronal degeneration. These compounds from C. officinalis could be potent nutraceutical agents with protective properties that may shield dopaminergic neurons against the damage caused by PD. Our findings provide a basis for utilizing the C. officinalis flowers in functional foods.

Limit theorems for the site frequency spectrum of neutral mutations in an exponentially growing population.

The site frequency spectrum (SFS) is a widely used summary statistic of genomic data. Motivated by recent evidence for the role of neutral evolution in cancer, we investigate the SFS of neutral mutations in an exponentially growing population. Using branching process techniques, we establish (first-order) almost sure convergence results for the SFS of a Galton-Watson process, evaluated either at a fixed time or at the stochastic time at which the population first reaches a certain size. We finally use our results to construct consistent estimators for the extinction probability and the effective mutation rate of a birth-death process.

Comprehensive profiling of L1 retrotransposons in mouse.

L1 elements are retrotransposons currently active in mammals. Although L1s are typically silenced in most normal tissues, elevated L1 expression is associated with a variety of conditions, including cancer, aging, infertility, and neurological disease. These associations have raised interest in the mapping of human endogenous de novo L1 insertions, and a variety of methods have been developed for this purpose. Adapting these methods to mouse genomes would allow us to monitor endogenous in vivo L1 activity in controlled, experimental conditions using mouse disease models. Here we use a modified version of transposon insertion profiling, called nanoTIPseq, to selectively enrich young mouse L1s. By linking this amplification step with nanopore sequencing, we identified >95% annotated L1s from C57BL/6 genomic DNA using only 200,000 sequencing reads. In the process, we discovered 82 unannotated L1 insertions from a single C57BL/6 genome. Most of these unannotated L1s were near repetitive sequence and were not found with short-read TIPseq. We used nanoTIPseq on individual mouse breast cancer cells and were able to identify the annotated and unannotated L1s, as well as new insertions specific to individual cells, providing proof of principle for using nanoTIPseq to interrogate retrotransposition activity at the single cell level in vivo .

The beneficial effects of the active components from Maclura tricuspidata fruits in the treatment of diabetes mellitus.

Five active compounds, daidzein, luteolin, alpinumisoflavone (AI), 6,8-diprenylgenistein (DG), and warangalone (WA), were identified from the fruits of Maclura tricuspidata via LC-Q/TOF-MS. WA and DG were shown to reverse the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs), indicating their potential protective effects in alleviating diabetic symptoms. Network pharmacology was conducted to reveal the potential mechanisms of action of the compounds, and Hsp90α (degree: 47), Src (degree: 49), Akt (degree: 69) and p53 (degree: 60) were shown as the core targets related to antidiabetic properties. Further experimental verification suggested that the compounds could enhance phosphorylation of Src and Akt, increase p53 expression act as Hsp90 inhibitors, and protect against HG induced endothelial dysfunction. Our findings will provide a comprehensive understanding of the active substances of M. tricuspidata, which will be helpful for their utilisation.

Long-infrared dual-wavelength linear-polarization-multiplexed confocal metalens based on an all-silicon dielectric.

The metalens has vast applications in biomedicine and industrial manufacturing due to their ultrathin structure and vital ability to manipulate the properties of light waves for long-infrared systems. However, it is difficult for metalens to achieve the confocal function with high focusing efficiency, wide wavelength bandwidth, and low structural complexity. Here, we propose and experimentally demonstrate an all-silicon dielectric metalens composed of arrays of minimalist meta-atoms with a single rectangular nanopillar arranged on a periodic square lattice substrate, which realizes the confocal function of the orthogonal-linear-polarized light with wavelengths of 10.6 µm and 9.3 µm, with focusing efficiencies of 64.94% and 60.03%, respectively. Also, it reveals nearly the diffraction-limited focusing performance. In addition, the metalens can realize precise long-infrared thermal imaging. Moreover, the proposed metalens is compatible with the standard complementary metal oxide semiconductor processes, which can effectively reduce the manufacturing cost and provide a feasible solution for developing planar integrated multifunctional micro-nanophotonic devices in the long-infrared field.

Secondary metabolites from the marine-derived fungus Penicillium chrysogenum Y20-2, and their pro-angiogenic activity.

A systematic chemical study of the secondary metabolites of the marine fungus, Penicillium chrysogenum (No. Y20-2), led to the isolation of 21 compounds, one of which is new (compound 3). The structures of the 21 compounds were determined by conducting extensive analysis of the spectroscopic data. The pro-angiogenic activity of each compound was evaluated using a zebrafish model. The results showed that compounds 7, 9, 16, and 17 had strong and dose-dependent pro-angiogenic effects, with compound 16 demonstrating the strongest pro-angiogenic activity, compounds 6, 12, 14, and 18 showing moderate activity, and compounds 8, 13, and 19 exhibiting relatively weak activity.

Xylenol orange-modified CdTe quantum dots as a fluorescent/colorimetric dual-modal probe for anthrax biomarker based on competitive coordination.

Bacillus anthracis spores can make humans infected with vicious anthrax, so it is significant to detect their biomarker 2,6-pyridinedicarboxylic acid (DPA). The development of dual-modal methods for DPA detection that are more flexible in practical applications remains a challenge. Herein, colorimetric xylenol orange (XO) was modified on fluorescent CdTe quantum dots (QDs) for dual-modal detection of DPA through competitive coordination. After the binding of XO on CdTe QDs via coordination with Cd2+, CdTe QDs displayed quenched red fluorescence and the bound XO was presented as red color. The competitive coordination of DPA with Cd2+ made XO released from CdTe QDs, causing the enhanced red fluorescence of CdTe QDs and the yellow color of free XO. On this basis, DPA was rapidly (1 min) quantified through fluorescent and colorimetric modes within the ranges of 0.1-5 µM and 0.5-40 µM, respectively. The detection limits for DPA were calculated as low as 42 nM and 240 nM, respectively assigned to fluorescent and colorimetric modes. The level of urinary DPA was further measured. Satisfactory relative standard deviations (fluorescent mode: 0.1%-10.2%, colorimetric mode: 0.8%-1.8%) and spiked recoveries (fluorescent mode: 100.0%-115.0%, colorimetric mode: 86.0%-96.6%) were obtained.

LC-MS Analysis of Ginsenosides in Different Parts of Panax quinquefolius and Their Potential for Coronary Disease Improvement.

Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb1, pseudoginsenoside F11, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd, and ginsenoside F2, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of Panax quinquefolius. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand-receptor interaction, cholesterol metabolism, the cGMP-PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the whole P. quinquefolius plant in drugs and functional foods.

[Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway].

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Radix Panacis quinquefolii Extract Ameliorates Inflammatory Bowel Disease through Inhibiting Inflammation.

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION: RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.

Bifunctional ratiometric fluorescent probe for sensing anthrax spore biomarker and tetracycline at different excitation channels.

Multifunctional fluorescent probes have received increasing attention for the sake of atom economy and high-density integration. Herein, CdTe quantum dots (QDs) modified with Eu3+ were synthesized as the bifunctional ratiometric fluorescent probe for sensing two hazardous substances tetracycline (TC) and anthrax spore biomarker 2,6-dipicolinic acid (DPA) at different excitation channels, based on the discrepant excitation wavelengths of Eu3+ and the fluorescence quenching of CdTe QDs after interaction with them. Both DPA and TC enhanced the red emission of Eu3+ via antenna effect but caused the green emission of CdTe QDs to quench. Interestingly, the excitation wavelengths of Eu3+ after coordinating with DPA and TC were 275 and 386 nm, respectively. On this basis, CdTe QDs-Eu3+ achieved the bifunctional ratiometric detection of DPA (λex = 275 nm) and TC (λex = 386 nm) with different excitation channels. Both DPA and TC were selectively detected by CdTe QDs-Eu3+ with rapid response (DPA-1 min, TC-1 min) and high sensitivity (DPA-LOD 0.3 µM, TC-LOD 2.2 nM). CdTe QDs-Eu3+ were applied to analyzing DPA and TC in food, biological and environmental samples. Satisfactory spiked recoveries (80.0-119.0 %) and relative standard deviations (0.5-8.4 %) were obtained for measuring DPA and TC in these samples.

Impact of Stone Powder Content on Corrosion Resistance in Reinforced Concrete under Stray Current and Chloride Interactions.

Manufactured sand, known for its artificial production, eco-friendliness, cost-effectiveness, and sustainability, serves as an excellent alternative to natural sand. Stone powder content plays a crucial role in determining the performance of manufactured sand, significantly enhancing concrete compaction and its ability to withstand environmental degradation. This study aims to explore the feasibility of using environmentally and economically advantageous manufactured sand in the construction of subway tunnel segments in coastal areas. It investigates the impact of stone powder content on the corrosion resistance of concrete made with manufactured sand under the combined influence of chloride salts and stray currents. The analysis covers corrosion tendencies, the post-rusting performance of reinforcement bars, the resistance of concrete to chloride transport, and microstructure properties, which are assessed through electron microscope scanning and mercury compression testing. The findings indicate that the corrosion resistance of manufactured sand concrete generally surpasses that of river sand concrete. Furthermore, stone powder content within the 3-8% range leads to a denser concrete microstructure, reduced porosity, lower free-chloride ion levels, increased polarization resistance of post-corrosion reinforcements, lower corrosion current density, and reduced mass loss of reinforcing bars. This research provides valuable theoretical support for promoting the use of environmentally friendly manufactured sand concrete in subway construction projects.

Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

Lipid Profiles of the Heads of Four Shrimp Species by UPLC-Q-Exactive Orbitrap/MS and Their Cardiovascular Activities.

Lipids are key factors in nutrition, structural function, metabolic features, and other biological functions. In this study, the lipids from the heads of four species of shrimp (Fenneropenaeus chinensis (FC), Penaeus japonicus (PJ), Penaeus vannamei (PV), and Procambarus clarkia (PCC)) were compared and characterized based on UPLC-Q-Exactive Orbitrap/MS. We compared the differences in lipid composition of four kinds of shrimp head using multivariate analysis. In addition, a zebrafish model was used to evaluate pro-angiogenic, anti-inflammatory, anti-thrombotic, and cardioprotective activities of the shrimp head lipids. The lipids from the four kinds of shrimp head had different degrees of pro-angiogenic activities, and the activities of PCC and PJ shrimp lipids were more significant than those of the other two species. Four lipid groups displayed strong anti-inflammatory activities. For antithrombotic activity, only PCC (25 µg/mL) and PV (100 µg/mL) groups showed obvious activity. In terms of cardioprotective activity, the four kinds of lipid groups significantly increased the zebrafish heart rhythms. The heart distances were shortened, except for those of the FC (100 µg/mL) and PJ (25 µg/mL) groups. Our comprehensive lipidomics analysis and bioactivity study of lipids from different sources could provide a basis for the better utilization of shrimp.

Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-ß-boswellic acid (AKBA) through oxidative stress.

Acetyl-11-keto-ß-boswellic acid (AKBA), a triterpenoid from Boswellia serrate, is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its developmental toxicity and cardiotoxicity. A developmental toxicity assay in zebrafish embryos/larvae from 4 to 96 hours post-fertilization (hpf) was performed and a cardiotoxicity assay was designed from 48 to 72 hpf. Markers of oxidative stress and related genes were selected to access the possible mechanisms. According to the results, AKBA induced pericardium edema, yolk-sac edema, abnormal melanin, spinal curvature, hatching inhibition and shortened body length. Further, increased SV-BA distance, reduced heart rate, increased pericardium area and decreased blood flow velocity were detected in AKBA treated groups. The inhibition of cardiac progenitor gene expression, such as Nkx2.5 and Gata4, may be related to cardiotoxicity. The activities of antioxidant enzymes were decreased and the content of MDA was increased. In addition, AKBA treatment decreased the expression levels of Mn-Sod, Cat, and Gpx. These results suggested that AKBA induced developmental toxicity and cardiotoxicity through oxidative stress. As far as we know, this is the first report on the toxicity of AKBA. It reminds us to pay attention to developmental toxicity and cardiotoxicity of AKBA.

Preparation and characterization of young Prunus persica fruit fraction and its anti-inflammatory effect on a transgenic zebrafish model.

Young Prunus persica fruits (YPF) contain substances that are distinct from those found in the mature fruits. Response surface methodology was used to explore the influences of extraction conditions including ultrasonic time (X1), ethanol proportion (X2), liquid-to-solid ratio (X3) and temperature (X4) on UV-absorbing components from YPF. To purify the extract, the adsorption/desorption properties of 280 nm-absorbing components on AB-8 resin were investigated. A total of 11 metabolites (amino acids, glycosylated amino acids and phenolics) were identified in the UV-absorbing fraction of YPF (YPF-F) based on LC-MS/MS assays. In a study of in vivo anti-inflammatory activity, YPF-F significantly decreased the number of inflammatory cells that migrated to the lateral line location in CuSO4-induced transgenic fluorescent zebrafish. YPF should be utilized as a high value resource of functional foods.[Formula: see text].