FACT mediates the depletion of macroH2A1.2 to expedite gene transcription.

The histone variant macroH2A is generally linked to transcriptionally inactive chromatin, but how macroH2A regulates chromatin structure and functions in the transcriptional process remains elusive. This study reveals that while the integration of human macroH2A1.2 into nucleosomes does not affect their stability or folding dynamics, it notably hinders the maintenance of facilitates chromatin transcription's (FACT's) function. We show that FACT effectively diminishes the stability of macroH2A1.2-nucleosomes and expedites their depletion subsequent to the initial unfolding process. Furthermore, we identify the residue S139 in macroH2A1.2 as a critical switch to modulate FACT's function in nucleosome maintenance. Genome-wide analyses demonstrate that FACT-mediated depletion of macroH2A-nucleosomes allows the correct localization of macroH2A, while the S139 mutation reshapes macroH2A distribution and influences stimulation-induced transcription and cellular response in macrophages. Our findings provide mechanistic insights into the intricate interplay between macroH2A and FACT at the nucleosome level and elucidate their collective role in transcriptional regulation and immune response of macrophages.

Rapid Prototyping of Thermoplastic Microfluidic 3D Cell Culture Devices by Creating Regional Hydrophilicity Discrepancy.

Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost-effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, an approach to pattern fluid guides inside microchannels is introduced by establishing differential hydrophilicity using pressure-sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. Optimal coating conditions are identified using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open-chip prototype and the fully bonded device containing additional features for medium perfusion. The suitability of the device for dynamic 3D cell culture is tested by growing human hepatocytes in the device under controlled fluid flow for a 14-day period. Additionally, the study demonstrated the potential of using the device for pharmaceutical high-throughput screening applications, such as predicting drug-induced liver injury. The approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.

Efficient Deep Learning Architecture for Detection and Recognition of Thyroid Nodules.

Ultrasonography is widely used in the clinical diagnosis of thyroid nodules. Ultrasound images of thyroid nodules have different appearances, interior features, and blurred borders that are difficult for a physician to diagnose into malignant or benign types merely through visual recognition. The development of artificial intelligence, especially deep learning, has led to great advances in the field of medical image diagnosis. However, there are some challenges to achieve precision and efficiency in the recognition of thyroid nodules. In this work, we propose a deep learning architecture, you only look once v3 dense multireceptive fields convolutional neural network (YOLOv3-DMRF), based on YOLOv3. It comprises a DMRF-CNN and multiscale detection layers. In DMRF-CNN, we integrate dilated convolution with different dilation rates to continue passing the edge and the texture features to deeper layers. Two different scale detection layers are deployed to recognize the different sizes of the thyroid nodules. We used two datasets to train and evaluate the YOLOv3-DMRF during the experiments. One dataset includes 699 original ultrasound images of thyroid nodules collected from a local health physical center. We obtained 10,485 images after data augmentation. Another dataset is an open-access dataset that includes ultrasound images of 111 malignant and 41 benign thyroid nodules. Average precision (AP) and mean average precision (mAP) are used as the metrics for quantitative and qualitative evaluations. We compared the proposed YOLOv3-DMRF with some state-of-the-art deep learning networks. The experimental results show that YOLOv3-DMRF outperforms others on mAP and detection time on both the datasets. Specifically, the values of mAP and detection time were 90.05 and 95.23% and 3.7 and 2.2 s, respectively, on the two test datasets. Experimental results demonstrate that the proposed YOLOv3-DMRF is efficient for detection and recognition of thyroid nodules for ultrasound images.