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Myocardial ischemia-reperfusion injury (MIRI) is a prevalent complication in patients with myocardial infarction. The pathological mechanism of MIRI remains elusive. Ferroptosis plays a critical role in MIRI. This study aimed to investigate the role of spermidine/spermine N1-acetyltransferase 1 (Sat1) in MIRI by regulation of ferroptosis. Rats and H9C2 cells were used to perform MIRI model. The extent of myocardial damage and associated pathological changes were evaluated. Protein expression was detected by western blot. Then we observed the mitochondrial morphology and measured cell viability and damage. The levels of lipid peroxide and glutathione were measured, and lipid reactive oxygen species (ROS) was quantified. Differentially expressed genes (DEGs) in MIRI were analyzed. Moreover, to explore the role of Sat1 in MIRI, this study utilized adeno-associated virus 9 and lentiviral transduction to modulate Sat1 expression in rats and H9C2 cells, respectively. The transcription factor that regulates Sat1 expression was predicated. Luciferase reporter gene experiment was conducted to reveal the potential sites of Sox2 binding to Sat1. This study revealed that ferroptosis was involved in MIRI. Through bioinformatic analysis, Sat1 was identified as a significant gene in MIRI, which has been reported as an inducer of ferroptosis. Our results showed that Sat1 expression was significantly increased in MIRI. Next, the study showed that inhibition of Sat1 alleviated MIRI by suppressing ferroptosis in vivo and , and over-expression of Sat1 promoted MIRI via activation of ferroptosis. Furthermore, Sat1 and its interacting genes were enriched in several signaling pathways, including ferroptosis and the MAPK signaling pathway. The results showed that Sat1 regulated MIRI through ferroptosis via MAPK/ERK pathway. Moreover, it is found that Sox2 can suppress Sat1 expression at the transcriptional level. The potential binding site was TAACAAAGGAA. In sum, this study demonstrated Sat1 expression was increased in MIRI, inhibition of Sat1 can alleviate MIRI by regulating ferroptosis via MAPK/ERK pathway, and Sat1 was negatively regulated by Sox2. These findings suggested that Sat1 may serve as a potential therapeutic target for the treatment of MIRI.

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference ( P  < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

Tongue muscles are derived from mesodermal cells, while signals driven by cranial neural crest cells (CNCCs) regulate tongue myogenesis via tissue–tissue interaction. Based on such mechanisms of interaction, congenital tongue defects occur in CNC-related syndromes in humans. This study utilized a pathologic model for the syndrome of congenital bony syngnathia, Wnt1-Cre;pMes-Bmp4 mouse line, to explore impacts of enhanced CNCCs-originated BMP4 signal on tongue myogenesis via tissue-tissue interaction. Our results revealed that microglossia, a clinical phenotype of congenital bony syngnathia in humans exhibited in Wnt1-Cre;pMes-Bmp4 mice due to impaired myogenesis. The augmented BMP4 signal affected the distal distribution, proliferation, and differentiation of myogenic cells as well as tendon patterning, resulting in disarrangement and atrophy of tongue muscles and the loss of the anterior digastric muscle. This study demonstrated how a CNCCs-originated ligand impaired tongue myogenesis via a non-autonomous way, which provided potential formation mechanisms for understanding tongue abnormalities in CNC-related syndromes.

To overcome the overheating phenomena of electronic devices and energy components, developing advanced energy‐free cooling coatings with promising radiative property seem an effective and energy‐saving way. However, the further application of these coatings is greatly limited by their sustainability because of their fragile and easy contamination. Herein, it is reported that a bioinspired radiative cooling coating (BRCC) displayed sustainably efficient heat dissipation by the combination of high emittance and robust self‐cleaning property. With the hierarchical porous structure constructed by multiwalled carbon nanotubes (MWCNTs), modified SiO2 and fluorosilicone (FSi) resin, the involvement of the BRCC improves the cooling performance by increasing ≈25% total heat transfer coefficient. During the abrasion and soiling tests, the BRCC‐coated Al alloy heat sink always displays stable radiative cooling performance. Moreover, the simulation and experimental results both revealed that reducing surface coverage of BRCC (≈80.9%) can still keep highly cooling efficiency, leading to a cost‐effective avenue. Therefore, this study may guide the design and fabrication of advanced radiative cooling coating. Inspired by the lotus leaves, we present a bio‐inspired radiative cooling coating (BRCC) with hierarchical porous structures, consisting of multiwalled carbon nanotubes, modified SiO2 and fluorosilicone resin. The BRCC displayed sustainably efficient heat dissipation by the combination of high emittance and robust self‐cleaning property. It is expected to be a promising candidate for thermal management applications for power‐intensive energy components.

Background Methylmalonic acidemia (MMA) is one of the most common hereditary organic acid metabolism disorders that endangers the lives and health of infants and children. Early detection and intervention before the appearance of a newborn’s clinical symptoms can control disease progression and prevent or mitigate its serious consequences. Methods 42,004 newborns from two Chinese populations were included in the study. The small molecular metabolite analytes were detected from the dried blood spot (DBS) samples by MS/MS. Genetic analysis of 68 Chinese MMA cases were performed by whole-exome sequencing and Sanger sequencing. Random forest classifiers (RFC) were constructed to improve the MMA screening performance and genotype prediction in two Chinese populations. Meanwhile, other six machine learning models were trained to separate MMA patients from normal newborns. Model performance was assessed using accuracy, sensitivity, specificity, false positive rate (FPR), and positive predictive value (PPV) and the area under the receiver operating characteristic curve (AUC). Results In the total 42,004 newborn samples, 68 MMA cases were identified by genetic analysis, 42 cases of which were caused by variants in MMACHC , 24 cases by variants in MMUT , and two cases by variants in MMAA . Three novel variants including c.449T>G (p.I150R) of MMACHC , c.1151C>T (p.S384F) and c.1091_1108delins (p.Y364Sfs*4) in MMUT were identified in the MMA patients. RFC for newborn screening of MMA performed best as compared to several other classification models based on machine learning with 100% sensitivity, low FPR, excellent PPV and AUC. In addition, the subdivision RFC for MMA genotype prediction was constructed with superior performance. Conclusions It can be seen that RFC is extremely helpful for detection and genotype prediction in the newborn MMA screening. In addition, our findings extend the variant spectrum of genes related to MMA.

Our goal is to assess the ability of physicians to detect coronary calcifications in dual energy chest X-rays processed by a previously developed advanced algorithm. Because the chest X-ray is the most common imaging procedure, because the presence of coronary calcium provides proof of coronary artery disease, and because adherence to therapy can improve health, successful detection could positively impact healthcare for a large number of patients. Both dual energy chest and corroborative CT calcium score images were acquired. Dual energy images were processed with the advanced techniques, including sliding organ registration, so as to enhance coronary calcifications in two-shot dual energy acquisitions. We performed ROC to determine physicians’ ability to detect coronary calcifications. Since detection might be easier with heavier calcifications, we used various Agatston score cut-points for determining cases actually positive with calcification in the ROC analysis. In many cases, coronary calcifications were made more visible with the advanced processing as compared to conventional processing. At an Agatston cut-point of 300, coronary calcifications were detected with AUC = 0.85. There were marginal effects on detection performance found with increased X-ray exposure, nearby Agatston cut-point values, and coronary artery territory. Coronary calcifications can be detected in dual energy chest X-rays. The ability to detect disease compares very favorably to other accepted screening methods (e.g., X-ray mammography). As the chest X-ray is an already ordered procedure, there is an opportunity to detect a very large number of persons with coronary artery disease at zero or low cost.

Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.

Background Although adult human tissue-derived epidermal stem cells are capable of differentiating into enamel-secreting ameloblasts and forming teeth with regenerated enamel when recombined with mouse dental mesenchyme that possesses odontogenic potential, the induction rate is relatively low. In addition, whether the regenerated enamel retains a running pattern of prism identical to and acquires mechanical properties comparable with human enamel indeed warrants further study. Methods Cultured human keratinocyte stem cells (hKSCs) were treated with fibroblast growth factor 8 (FGF8) and Sonic hedgehog (SHH) for 18 h or 36 h prior to being recombined with E13.5 mouse dental mesenchyme with implantation of FGF8 and SHH-soaked agarose beads into reconstructed chimeric tooth germs. Recombinant tooth germs were subjected to kidney capsule culture in nude mice. Harvested samples at various time points were processed for histological, immunohistochemical, TUNEL , and western blot analysis. Scanning electronic microscopy and a nanoindentation test were further employed to analyze the prism running pattern and mechanical properties of the regenerated enamel. Results Treatment of hKSCs with both FGF8 and SHH prior to tissue recombination greatly enhanced the rate of tooth-like structure formation to about 70%. FGF8 and SHH dramatically enhanced stemness of cultured hKSCs. Scanning electron microscopic analysis revealed the running pattern of intact prisms of regenerated enamel is similar to that of human enamel. The nanoindentation test indicated that, although much softer than human child and adult mouse enamel, mechanical properties of the regenerated enamel improved as the culture time was extended. Conclusions Application of FGF8 and SHH proteins in cultured hKSCs improves stemness but does not facilitate odontogenic fate of hKSCs, resulting in an enhanced efficiency of ameloblastic differentiation of hKSCs and tooth formation in human–mouse chimeric tooth germs.

With the rapid development of deep learning, convolutional neural networks have been applied to no-reference image quality assessment (NR-IQA), but most methods focus on the design of complex networks, which not only increase network parameters and make the training process more difficult, but also fail to make full use of the rich global and local information in images. To address this problem, this paper proposed an effective NR-IQA method, namely, attention-driven residual dense network, which can evaluate the quality of images quickly and accurately. Specifically, three different sizes of convolution kernels are first used to extract features from images by parallel, so that the feature information of images can be expressed at different scales. Next, several cascaded residual dense channel attention blocks are used to further extract high-level feature information, which can capture the most effective feature. In addition, we embed a novel channel attention mechanism into the multi-scale feature extraction block and the residual dense block to filter out channel-specific attention by learning correlations between channels. A series of experiments on public synthetic databases show that the proposed method outperforms the state-of-the-art NR-IQA methods.