High-frequency rTMS of the left dorsolateral prefrontal cortex for post-stroke depression: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the therapeutic efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for treatment of post-stroke depression (PSD). METHODS: Ten articles with 266 patients in rTMS group and 258 patients in control group were included. The primary outcome was performed to examine the efficacy of rTMS for PSD. Secondary outcomes of response rates and remission rates and subgroup analyses were further explored. RESULTS: Our meta-analysis revealed a significant pooled effect size (the standard mean difference (SMD) was -1.45 points (95% CI, -2.04 to -0.86; p < 0.00001)). The odds ratio (OR) of the response rate and remission rate were 8.41 (95% CI, 2.52-28.12, p = 0.0005) and 6.04 (95% CI, 1.5-24.39, p = 0.01). Moreover, rTMS treatment for PSD patients in subacute phase and targeting the left DLPFC at 5-cm anterior to the left motor hotspot or the midpoint of the middle frontal gyrus showed significant antidepressant effect. In addition, the Hamilton Depression Rating Scale (HAMD) was sensitive to detect depressive changes in patients. CONCLUSIONS: Our meta-analysis elucidated that the application of high-frequency rTMS over the left DLPFC was an effective treatment alternative for PSD. SIGNIFICANCE: Our meta-analysis may help to develop more reasonable treatment strategies in clinical practice for PSD patients.

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus.

Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the Saccharomyces cerevisiae endocytic protein Ede1, in Aspergillus fumigatus. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of edeA caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the edeA null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in A. fumigatus. This observation was further supported by the evidence showing that the thickness of the cell wall in the ΔedeA mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the ΔedeA mutant displayed increased pathogenicity in the Galleria mellonella wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (Eps15 homology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in A. fumigatus. IMPORTANCE: Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.

Phycosphere bacterial disturbance of Saccharina japonica caused by white rot disease relates to seawater nutrients.

In mid-November 2021, there were large areas of white rot disease on cultivated Saccharina japonica in Rongcheng City, China, and diseases were undetected on Sargassum horneri and Porphyra yezoensis. The disturbance direction of bacterial community in the phycosphere after disease outbreak and the relationship with seawater nutrients remain unclear. Here, in situ studies of bacterial community in the non-diseased and diseased areas (Shawo and Dongchu islands) and seawater nutrient levels were carried out. 16S rRNA sequencing showed that the bacterial richness of the studied seaweeds increased in the diseased area. Only in S. japonica, Algitalea outcompeted abundant primary bacteria with probiotic relationships to the host of the non-diseased area, and dominated in the diseased area (17.6% of the total abundance). Nitrogen and phosphorus levels in seawater were 57.8% and 19.6% higher in the non-diseased area than those in the diseased area, respectively, and were strongly correlated with the phycosphere bacteria at the family level of S. japonica. There was no difference in potential pathogenicity between the two areas, while positive signal communications decreased, and nitrogen cycle, chemoheterotrophy, and cellulolysis increased in the diseased area compared to the non-diseased area. Overall, white rot disease caused a structural disturbance in phycosphere bacterial community of S. japonica that related to seawater nutrient levels. Enriched degraders and altered bacterial community functions may exacerbate the disease. This evaluation will provide information for white rot disease management to prevent and mitigate the occurrence of S. japonica outbreaks.