Differential Proteomic Analysis of Low-Dose Chronic Paralytic Shellfish Poisoning.

Shellfish poisoning is a common food poisoning. To comprehensively characterize proteome changes in the whole brain due to shellfish poisoning, Tandem mass tag (TMT)-based differential proteomic analysis was performed with a low-dose chronic shellfish poisoning model in mice. A total of 6798 proteins were confidently identified, among which 123 proteins showed significant changes (fold changes of >1.2 or <0.83, p < 0.05). In positive regulation of synaptic transmission, proteins assigned to a presynaptic membrane (e.g., Grik2) and synaptic transmission (e.g., Fmr1) changed. In addition, altered proteins in nervous system development were observed, suggesting that mice suffered nerve damage due to the nervous system being activated. Ion transport in model mice was demonstrated by a decrease in key enzymes (e.g., Kcnj11) in voltage-gated ion channel activity and solute carrier family (e.g., Slc38a3). Meanwhile, alterations in transferase activity proteins were observed. In conclusion, these modifications observed in brain proteins between the model and control mice provide valuable insights into understanding the functional mechanisms underlying shellfish poisoning.

Relationship Between Genetic Polymorphism and Cognitive Impairment in Patients with Acute Ischemic Stroke (APOE).

Objective: To investigate the relationship between apolipoprotein E (ApoE) gene polymorphism and cognitive impairment (PSCI) in patients after acute ischemic stroke (AIS). Methods: A total of 150 AIS patients were treated in Chengde Central Hospital from December 2022 to December 2023 and were selected and divided into a disorder group (n=88) and a normal group (n=62) according to the presence or absence of PSCI. Clinical data of patients in the two groups were collected, ApoE genotype and allele distribution of patients in the disabled group and the normal group were detected, Montreal Cognitive Assessment and Mini-Mental State Examination scores of patients with different ApoE gene subtypes were compared, and the risk factors of PSCI after AIS were analyzed by unconditional Logistic regression. Results: The proportion of patients with acute lesions (≥3.0 cm) and the degree of carotid artery stenosis (moderate, severe, complete occlusion) in the disorder group was higher than that in the normal group, and the National Institutes of Health Stroke Scale score was higher than that in the control group, with statistical significance (P < .05). There were significant differences in the genotype and allelic distribution of ApoE between the two groups (P < .05). In both groups, the highest genotype frequency of ApoE was the ε3/3 homozygous type, which was 47.73% (in the disorder group) and 72.58% (in the normal group) respectively. In contrast, there were no significant differences in the genotype frequencies of ε2/2, ε2/3, ε2/4 and ε4/4 alleles in the two groups (P > .05). This means that in both groups of patients, the frequency of the ApoE ε3/3 genotype was the highest, while the genotype frequencies of ε2/2, ε2/3, ε2/4 and ε4/4 alleles were not significant between the two groups. difference. The distribution differences of these genotypes and alleles may be related to aspects such as disease risk and physiological function, providing valuable information for in-depth exploration of the role of ApoE in patients. The genotype frequency of ε3/3 in the disorder group was lower than that in the normal group. The frequency of the ε3/4 genotype was higher than that of the normal group, and the difference was statistically significant (P < .05). In both groups, the highest allele frequency was ε3 (68.75% in the disorder group and 83.06% in the normal group), and there was no difference in the frequency of ε2 allele between the two groups (P > .05). The frequency of the ε3 allele in the disorder group was lower than that in the normal group, and the frequency of the ε4 allele was higher than that in the normal group, the difference was statistically significant (P < .05). In the patients with cognitive impairment after AIS (disorder group), the MOCA and MMSE scores of patients with different ApoE subtypes (ε2, ε3, ε4) were compared, and the differences among the three groups were statistically significant (P < .05). The MOCA and MMSE scores in the ε4 group were lower than those in the ε2 and ε3 groups. The difference was statistically significant (P < .05). Logistic regression analysis showed that the degree of carotid artery stenosis, NIHSS score, and ApoEε4 gene were independent risk factors for PSCI in patients with AIS (P < .05). Conclusion: APOE gene polymorphism is associated with cognitive impairment in post-AIS patients, and carrying the ApoE Epsilon 4 gene may be associated with PSCI in post-AIS patients.

Microbial community diversity from nearshore to offshore in the East China Sea.

The Pollution Nagasaki (PN) section of the East China Sea (ECS) is a typical area for studying the complex hydrographic dynamics between Changjiang River discharge and Kuroshio, displaying intense variations of environmental gradients from nearshore to offshore. However, the temporal and spatial changes of microbial communities along the PN section have long been overlooked. In this study, we performed a comprehensive investigation into the abundance, diversity and ecology of free-living (FL) and particle-associated (PA) microbial communities in seawater samples along the PN section during both summer and winter. Distinct hydrological conditions and resulting environmental gradients were observed between summer and winter, with clear features of intrusive Kuroshio subsurface water in summer and strong vertical mixing of seawater in winter. Bacterial abundance along the PN section was higher in summer (1.11 × 108 copies·L-1 - 7.37 × 108 copies·L-1) than in winter (1.83 × 106 copies·L-1 - 1.34 × 108 copies·L-1). Microbial diversity, as indicated by α-diversity indices, remained at relatively stable levels in summer, while a clear decreasing trend was observed in winter along the PN section. Additionally, the winter communities exhibited a more evident spatial shift along the PN section compared to the summer communities. 16S rRNA gene amplicon sequencing showed that microbial community composition varied considerably between different seasons (summer and winter) and lifestyles (FL and PA), with a notable dominance of Ralstonia species. in winter. Regarding the assembly of microbial communities, the stochastic process represented by dispersal limitation was the dominant process in summer, while the deterministic homogeneous selection was the most important process in winter. Correspondingly, distinct topological properties of the microbial co-occurrence networks were shown between different seasons and along the PN section. These results enhance our understanding of how hydrological conditions influence dynamic changes of microbial communities along the PN section, providing new insights for the microbial community assembly and interactions in such a complex environment.

Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.