Rhizopus arrhizus infection in mice causes brain histopathological alterations and exacerbates neuronal apoptosis.

Rhizopus arrhizus is a fungus that can cause central nervous system infections in animals, resulting in high morbidity and mortality, but the mechanism of injury is rarely reported. In this study, we investigated the mechanism of Rhizopus arrhizus damage to the central nervous system of mice by observing the clinical neurological symptoms and resolving the pathological changes in the ultrastructure of brain tissues, combined with the alteration of apoptosis-related genes and immunohistochemistry (IHC). The results showed that all the mice in the treated group died, the brain pyknosis of neurons, there were black mycelium aggregates around the blood vessels, and apoptotic vesicles were produced. The RT-qPCR results showed that, compared with the control group, the relative transcriptome levels of Caspase 8 and BcL-2 genes were significantly increased (P < 0.05), the relative transcriptome level of Caspase 9 gene was highly significant (P < 0.01), the relative transcriptome level of Caspase 3 and Bax gene was significantly decreased (P < 0.05), and the ratio of Bcl-2/Bax was significantly increased (P < 0.05) in the brains of the treated group. TUNEL staining showed that the rate of neuronal apoptosis in the treated group of mice was extremely significantly higher than that in the control group (P < 0.01). This study shows that Rhizopus arrhizus strain XMLO1 causes brain damage by triggering neuronal apoptosis. This study provided a theoretical basis for revealing the mechanism of Rhizopus arrhizus infection.

Impact of environmental variables on the distribution of phytoplankton communities in the Southern Yellow Sea.

To gain a comprehensive understanding of the seasonal variation in the structure of phytoplankton communities in the Southern Yellow Sea (SYS), two research expeditions were conducted from 12 to 24 in April 2019, and from 12 to 22 in October of 2019. During the spring season, the phytoplankton community within the SYS was primarily comprised of diatoms and dinoflagellates, while in autumn, diatoms and cyanobacteria dominated. Thalassiosira rotula and Paralia sulcata were the dominant species in both seasons. In spring, P. sulcata displayed no obvious correlation with any environmental parameter, while in autumn, it exhibited negative correlations with environmental factors. According to the cluster and multidimensional scaling analyses, the phytoplankton community was stratified into three distinct ecological provinces in the SYS: the Western Yellow Sea, the Yellow Sea basin, and the southern coastal region. The phytoplankton community composition was predominantly affected by seasonal fluctuations in temperature and nutrient levels. Notably, the Yellow Sea basin exhibited the lowest phytoplankton abundance, largely because of the impact of the Yellow Sea Cold Water Mass. Furthermore, the presence of cyanobacteria, particularly prevalent in the Yellow Sea basin, may have been facilitated by transport mechanisms associated with the Kuroshio current. Aggregated boosted tree (ABT) and Generalized Additive models (GAM) suggested that temperature, DIN, salinity, and DIP were significant parameters of phytoplankton abundance in SYS. Additionally, the N:P nutrient ratio was a key parameter in governing the structure of phytoplankton communities during both seasons.

Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy.

PURPOSE: This study aimed to characterize the clinical features, genetic findings, and genotype-phenotype correlations of patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD) harboring biallelic AIPL1 pathogenic variants. DESIGN: Retrospective case series. METHODS: This study consecutively enrolled 51 patients from 47 families with a clinical diagnosis of LCA/EOSRD harboring disease-causing variants in the AIPL1 gene, from October 2021 to September 2023. Molecular genetic findings, medical history, and ophthalmic evaluation including visual acuity (VA), multimodal retinal imaging, and electrophysiologic assessment were reviewed. RESULTS: Of the 51 patients (32 with LCA and 19 with EOSRD), 27 (53%) were females, and age at last review ranged from 0.5 to 58.4 years. We identified 28 disease-causing AIPL1 variants, with 18 being novel. In patients with EOSRD, the mean (range) VA was 1.3 (0.7-2.7) logMAR and 1.3 (0.5-2.3) logMAR for right and left eyes respectively, with an average annual decline of 0.03 logMAR (R2 = 0.7547, P < .01). For patients with LCA, the VA ranged from light perception to counting fingers. Optical coherence tomography imaging demonstrated preservation of foveal ellipsoid zone in the 5 youngest EOSRD patients and 9 LCA children. Electroretinography showed severe cone-rod patterns in 78.6% (11/14) of patients with EOSRD, while classical extinguished pattern was documented in all patients with LCA available for the examination. The most common mutation was the nonsense variants of c.421C>T, with an allele frequency of 53.9%. All patients with EOSRD carried at least one missense mutation, of whom 13 identified with c.152A>G and 5 with c.572T>C. Twenty-six patients with LCA harbored two null AIPL1 variants, while 18 were homozygous for c.421C>T and 6 were heterozygous for c.421C>T with another loss-of-function variant. CONCLUSIONS: This study reveals distinct clinical features and variation spectrum between AIPL1-associated LCA and EOSRD. Patients harboring at least one nonnull mutation, especially c.152A>G and c.572T>C, were significantly more likely to have a milder EOSRD phenotype than those with two null mutations. Residual foveal outer retinal structure observed in the youngest proportion of patients suggests an early window for gene augmentation therapy.