Cell cycle of microalga Isochrysis galbana arrested by neurotoxin ß-N-methylamino-l-alanine and corresponding molecular mechanisms.

The phycotoxin ß-N-methylamino-l-alanine (BMAA) has attracted attention due to its risks to marine organisms and human health. In this study, approximately 85 % of synchronized cells of the marine microalga Isochrysis galbana were arrested at the cell cycle G1 phase by BMAA at 6.5 µM for a 24-h exposure. The concentration of chlorophyll a (Chl a) gradually decreased, while the maximum quantum yield of PSII (Fv/Fm), the maximum relative electron transport rate (rETRmax), light utilization efficiency (α) and half-saturated light irradiance (Ik) reduced early and recovered gradually in I. galbana exposed to BMAA in 96-h batch cultures. Transcriptional expression of I. galbana analyzed at 10, 12, and 16 h disclosed multiple mechanisms of BMAA to suppress the microalgal growth. Production of ammonia and glutamate was limited by the down-regulation of nitrate transporters, glutamate synthase, glutamine synthetase, cyanate hydrolase, and formamidase. Diverse extrinsic proteins related to PSII, PSI, cytochrome b6f complex, and ATPase were influenced by BMAA at transcriptional level. Suppression of the DNA replication and mismatch repair pathways increased the accumulation of misfolded proteins, which was reflected by the up-regulated expression of proteasome to accelerate proteolysis. This study improves our understanding of the chemical ecology impacts of BMAA in marine ecosystems.

Occurrence and spatial distribution of paralytic shellfish toxins in seawater and marine organisms in the coastal waters of Qinhuangdao, China.

In recent years, paralytic shellfish toxins (PSTs) have been prevalent in the coastal waters of Qinhuangdao, the west coast of the Bohai Sea, China. The content of PSTs in shellfish often exceeded the regulatory limit of 800 µg STX equivalent (eq.) kg-1, which poses a serious threat to human health. In this study, two surveys were conducted in May 2021 and May 2022 to investigate the distribution of PSTs in the coastal waters of Qinhuangdao. Seawater, surface sediment, phytoplankton, zooplankton, and other marine organism samples were collected, and the composition and concentration of PSTs were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results showed that multiple PST components were detected in all seawater samples collected at different depths, mainly including GTX1/4, GTX2/3, dcGTX2, STX and C1/2, and the highest concentration of PSTs reached 244 ng STX eq. L-1. The sediment samples also contained low levels of C1/2 and GTX2/3. Trace amounts of C1/2 and GTX1-4 were detected in phytoplankton and zooplankton. Moreover, all bivalve shellfish samples were found to contain PSTs, and the scallop Azumapecten farreri and the ark clam Anadara kagoshimensis showed relatively high concentrations of 607 and 497 µg STX eq. kg-1, respectively. In addition, low levels of PSTs were also found in some non-traditional PST vectors, including whelk Rapana venosa, octopus Amphioctopus ovulum, goby Ctenotrypauchen chinensis, and greenling Hexagrammos agrammus. Results of this study improve the understanding of the distribution of PSTs in seawater and marine organisms and the potential risk of persistent PSTs in seawater to marine ecosystems and human health.

TSAb Modulates Microglia M1 Polarization via Activation of the TSHR-Mediated NF-κB Signaling Pathway.

INTRODUCTION: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. METHODS: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. RESULTS: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. CONCLUSIONS: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release.

Non-Gaussian fluctuations and non-Markovian effects in the nuclear fusion process: Langevin dynamics emerging from quantum molecular dynamics simulations.

Macroscopic parameters as well as precise information on the random force characterizing the Langevin-type description of the nuclear fusion process around the Coulomb barrier are extracted from the microscopic dynamics of individual nucleons by exploiting the numerical simulation of the improved quantum molecular dynamics. It turns out that the dissipation dynamics of the relative motion between two fusing nuclei is caused by a non-Gaussian distribution of the random force. We find that the friction coefficient as well as the time correlation function of the random force takes particularly large values in a region a little bit inside of the Coulomb barrier. A clear non-Markovian effect is observed in the time correlation function of the random force. It is further shown that an emergent dynamics of the fusion process can be described by the generalized Langevin equation with memory effects by appropriately incorporating the microscopic information of individual nucleons through the random force and its time correlation function.