Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

A Formal γ-C-H Functionalization of Carboxylic Acids Guided by Metal-Nitrenoids as an Unprecedented Mechanistic Motif.

Harnessing the key intermediates in metal-catalyzed reactions is one of the most essential strategies in the development of selective organic transformations. The nitrogen group transfer reactivity of metal-nitrenoids to ubiquitous C-H bonds allows for diverse C-N bond formation to furnish synthetically valuable aminated products. In this study, we present an unprecedented reactivity of iridium and ruthenium nitrenoids to generate remote carbocation intermediates, which subsequently undergo nucleophile incorporation, thus developing a formal γ-C-H functionalization of carboxylic acids. Mechanistic investigations elucidated a unique singlet metal-nitrenoid reactivity to initiate an abstraction of γ-hydride to form the carbocation intermediate that eventually reacts with a broad range of carbon, nitrogen, and oxygen nucleophiles, as well as biorelevant molecules. Alternatively, the same intermediate can lead to deprotonation to afford ß,γ-unsaturated amides in a less nucleophilic solvent.

Seasonal patterns and bloom dynamics of phytoplankton based on satellite-derived chlorophyll-a in the eastern yellow sea.

Satellite-derived chlorophyll-a concentration (Chl-a) is essential for assessing environmental conditions, yet its application in the optically complex waters of the eastern Yellow Sea (EYS) is challenged. This study refines the Chl-a algorithm for the EYS employing a switching approach based on normalized water-leaving radiance at 555 nm wavelength according to turbidity conditions to investigate phytoplankton bloom patterns in the EYS. The refined Chl-a algorithm (EYS algorithm) outperforms prior algorithms, exhibiting a strong alignment with in situ Chl-a. Employing the EYS algorithm, seasonal and bloom patterns of Chl-a are detailed for the offshore and nearshore EYS areas. Distinct seasonal Chl-a patterns and factors influencing bloom initiation differed between the areas, and the peak Chl-a during the bloom period from 2018 to 2020 was significantly lower than the average year in both areas. Specifically, bimodal and unimodal peak patterns in Chl-a were observed in the offshore and nearshore areas, respectively. By investigating the relationships between environmental factors and bloom parameters, we identified that major controlling factors governing bloom initiation were mixed layer depth (MLD) and suspended particulate matter (SPM) in the offshore and nearshore areas, respectively. Additionally, this study proposed that the recent decrease in the peak Chl-a might be caused by rapid environmental changes such as the warming trend of sea surface temperature (SST) and the limitation of nutrients. For example, external forcing, phytoplankton growth, and nutrient dynamics can change due to increased SST and limitation of nutrients, which can lead to a decrease in Chl-a. This study contributes to understanding phytoplankton dynamics in the EYS, highlighting the importance of region-specific considerations in comprehending Chl-a patterns and bloom dynamics.

Villoglandular Adenocarcinoma of the Uterine Cervix: A Case Report.

Cervical adenocarcinomas constitute for approximately 10%-20% of all invasive cervical cancers. Villoglandular adenocarcinomas (VGAs) are a rare subtype of cervical adenocarcinoma, representing approximately 5% of all cases of cervical adenocarcinomas. Herein, we report the case of a 49-year-old perimenopausal woman successfully treated for VGA. The patient presented to the hospital with a primary complaint of vaginal discharge persisting for 7 months with worsening symptoms. She had no underlying medical conditions or history of oral contraceptive use. A punch biopsy revealed an adenocarcinoma, and a human papillomavirus (HPV) test indicated positive for HPV-16. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection, and a pathological diagnosis of VGA was established. After surgery, the patient underwent a 6-week course of concurrent chemoradiotherapy with cisplatin. During the 42 months of follow-up, no signs of disease recurrence or metastasis were observed. Because of the limitations of specimen acquisition, achieving a precise diagnosis through cervicovaginal cytology and punch biopsy is challenging. Instead, conization should be considered to prevent misdiagnosis.