Transcriptome-wide N6-methyladenosine (m6A) methylation profiling of long non-coding RNAs in ovarian endometriosis.

N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.

SEnSCA: Identifying possible ligand-receptor interactions and its application in cell-cell communication inference.

Multicellular organisms have dense affinity with the coordination of cellular activities, which severely depend on communication across diverse cell types. Cell-cell communication (CCC) is often mediated via ligand-receptor interactions (LRIs). Existing CCC inference methods are limited to known LRIs. To address this problem, we developed a comprehensive CCC analysis tool SEnSCA by integrating single cell RNA sequencing and proteome data. SEnSCA mainly contains potential LRI acquisition and CCC strength evaluation. For acquiring potential LRIs, it first extracts LRI features and reduces the feature dimension, subsequently constructs negative LRI samples through K-means clustering, finally acquires potential LRIs based on Stacking ensemble comprising support vector machine, 1D-convolutional neural networks and multi-head attention mechanism. During CCC strength evaluation, SEnSCA conducts LRI filtering and then infers CCC by combining the three-point estimation approach and single cell RNA sequencing data. SEnSCA computed better precision, recall, accuracy, F1 score, AUC and AUPR under most of conditions when predicting possible LRIs. To better illustrate the inferred CCC network, SEnSCA provided three visualization options: heatmap, bubble diagram and network diagram. Its application on human melanoma tissue demonstrated its reliability in CCC detection. In summary, SEnSCA offers a useful CCC inference tool and is freely available at https://github.com/plhhnu/SEnSCA.

Contrast-enhanced CT radiomics for preoperative prediction of stage in epithelial ovarian cancer: a multicenter study.

BACKGROUND: Preoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset. METHODS: A total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test. RESULTS: Seven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P < 0.001). CONCLUSIONS: The combined model integrating clinical characteristics and radiomics features shows potential as a non-invasive adjunctive diagnostic modality for preoperative evaluation of the FIGO staging status of EOC, thereby facilitating clinical decision-making and enhancing patient outcomes.

RNA structure probing uncovers RNA structure-dependent biological functions.

RNA molecules fold into complex structures that enable their diverse functions in cells. Recent revolutionary innovations in transcriptome-wide RNA structural probing of living cells have ushered in a new era in understanding RNA functions. Here, we summarize the latest technological advances for probing RNA secondary structures and discuss striking discoveries that have linked RNA regulation and biological processes through interrogation of RNA structures. In particular, we highlight how different long noncoding RNAs form into distinct secondary structures that determine their modes of interactions with protein partners to realize their unique functions. These dynamic structures mediate RNA regulatory functions through altering interactions with proteins and other RNAs. We also outline current methodological hurdles and speculate about future directions for development of the next generation of RNA structure-probing technologies of higher sensitivity and resolution, which could then be applied in increasingly physiologically relevant studies.

Remote ischemic preconditioning and clinical outcomes after pediatric cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: The benefit of remote ischemia preconditioning (RIPreC) in pediatric cardiac surgery is unclear. The objective of this systematic review and meta-analysis was to examine the effectiveness of RIPreC in reducing the duration of mechanical ventilation and intensive care unit (ICU) length of stay after pediatric cardiac surgery. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to December 31, 2022. Randomized controlled trials comparing RIPreC versus control in children undergoing cardiac surgery were included. The risk of bias of included studies was assessed using the Risk of Bias 2 (RoB 2) tool. The outcomes of interest were postoperative duration of mechanical ventilation and ICU length of stay. We conducted random-effects meta-analysis to calculate weighted mean difference (WMD) with 95% confidence interval (CI) for the outcomes of interest. We performed sensitivity analysis to examine the influence of intraoperative propofol use. RESULTS: Thirteen trials enrolling 1,352 children were included. Meta-analyses of all trials showed that RIPreC did not reduce postoperative duration of mechanical ventilation (WMD -5.35 h, 95% CI -12.12-1.42) but reduced postoperative ICU length of stay (WMD -11.48 h, 95% CI -20.96- -2.01). When only trials using propofol-free anesthesia were included, both mechanical ventilation duration (WMD -2.16 h, 95% CI -3.87- -0.45) and ICU length of stay (WMD -7.41 h, 95% CI -14.77- -0.05) were reduced by RIPreC. The overall quality of evidence was moderate to low. CONCLUSIONS: The effects of RIPreC on clinical outcomes after pediatric cardiac surgery were inconsistent, but both postoperative mechanical ventilation duration and ICU length of stay were reduced in the subgroup of children not exposed to propofol. These results suggested a possible interaction effect of propofol. More studies with adequate sample size and without intraoperative propofol use are needed to define the role of RIPreC in pediatric cardiac surgery.

Gaze Estimation Based on Convolutional Structure and Sliding Window-Based Attention Mechanism.

The direction of human gaze is an important indicator of human behavior, reflecting the level of attention and cognitive state towards various visual stimuli in the environment. Convolutional neural networks have achieved good performance in gaze estimation tasks, but their global modeling capability is limited, making it difficult to further improve prediction performance. In recent years, transformer models have been introduced for gaze estimation and have achieved state-of-the-art performance. However, their slicing-and-mapping mechanism for processing local image patches can compromise local spatial information. Moreover, the single down-sampling rate and fixed-size tokens are not suitable for multiscale feature learning in gaze estimation tasks. To overcome these limitations, this study introduces a Swin Transformer for gaze estimation and designs two network architectures: a pure Swin Transformer gaze estimation model (SwinT-GE) and a hybrid gaze estimation model that combines convolutional structures with SwinT-GE (Res-Swin-GE). SwinT-GE uses the tiny version of the Swin Transformer for gaze estimation. Res-Swin-GE replaces the slicing-and-mapping mechanism of SwinT-GE with convolutional structures. Experimental results demonstrate that Res-Swin-GE significantly outperforms SwinT-GE, exhibiting strong competitiveness on the MpiiFaceGaze dataset and achieving a 7.5% performance improvement over existing state-of-the-art methods on the Eyediap dataset.

The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin.

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

Metal-Organic Framework Confined Solvent Ionic Liquid Enables Long Cycling Life Quasi-Solid-State Lithium Battery in Wide Temperature Range.

Solid-state Li batteries are receiving increasing attention as a prospective energy storage system due to the high energy density and improved safety. However, the high interfacial resistance between solid-state electrolyte and electrode results in sluggish Li+ transport kinetics. To tackle the interfacial problem and prolong the cycle life of solid-state Li batteries, a quasi-solid-state electrolyte (QSSE) based on a solvate ionic liquid (SIL) space-restricted in nanocages of UIO-66 (SIL/UIO-66) is prepared in this study. Benefiting from the effective spatial confinement of the TFSI- by the pore UIO-66 and the strong chemical interactions between the SIL and metal atoms, SIL/UIO-66 QSSE exhibits high ionic conductivity and good compatibility with electrodes. As a result, Li|QSSE|LFP cells demonstrate excellent rate capability and cycle stability in a wide temperature range of 25-90 °C. This study provides a realistic strategy for the fabrication of safe solid electrolytes with excellent compatibility and long cycle life for high-performance QSSE Li-ion batteries.

Development of a handheld compression optical coherence elastography probe with a disposable stress sensor.

Optical coherence elastography (OCE) is a functional extension of optical coherence tomography (OCT). OCE measures a sample's deformation under force stimuli. Compression is often used to generate the force stimuli in OCE. In this Letter, we report the development of a handheld quantitative compression OCE probe with a novel stress senor, dedicated to measuring the force. The stress sensor consists of a circular glass window and a metal ring which are connected with polyurethane spokes. This sensor is mounted on the tip of the OCT sample arm as an imaging window, so that the force applied to the sample through the window can be measured by detecting the window displacement from the OCT image. The force-displacement function was first developed through simulation on COMSOL Multiphysics and eventually calibrated experimentally. A phase-sensitive OCT technique was employed to measure both the window displacement and the sample deformation. The performance of an OCE probe with this stress sensor was evaluated on a two-layer phantom. The results show that it is extremely capable of measuring the sample Young's modulus. Finally, we successfully measured the elasticity of the human fingertip, indicating a good potential of this OCE probe for in vivo elastogram measurement on human skin.

New Insight into the Confinement Effect of Microporous Carbon in Li/Se Battery Chemistry: A Cathode with Enhanced Conductivity.

Embedding the fragmented selenium into the micropores of carbon host has been regarded as an effective strategy to change the Li-Se chemistry by a solid-solid mechanism, thereby enabling an excellent cycling stability in Li-Se batteries using carbonate electrolyte. However, the effect of spatial confinement by micropores in the electrochemical behavior of carbon/selenium materials remains ambiguous. A comparative study of using both microporous (MiC) and mesoporous carbons (MeC) with narrow pore size distribution as selenium hosts is herein reported. Systematic investigations reveal that the high Se utilization rate and better electrode kinetics of MiC/Se cathode than MeC/Se cathode may originate from both its improved Li+ and electronic conductivities. The small pore size (<1.35 nm) of the carbon matrices not only facilitates the formation of a compact and robust solid-electrolyte interface (SEI) with low interfacial resistance on cathode, but also alters the insulating nature of Li2 Se due to the emergence of itinerant electrons. By comparing the electrochemical behavior of MiC/Se cathode and the matching relationship between the diameter of pores and the dimension of solvent molecules in carbonate, ether, and solvate ionic liquid electrolyte, the key role of SEI film in the operation of C/Se cathode by quasi-solid-solid mechanism is also highlighted.

Dual-side view optical coherence tomography for thickness measurement on opaque materials.

Optical coherence tomography (OCT), as an optical interferometric imaging technique, has found wide applications in various fields. In principle, OCT is well suited for imaging layered structures, and thus, one of the typical applications is thickness measurement. However, due to the limited imaging depth resulting from light attenuation, thickness measurement by OCT is limited to non-opaque materials. In this study, we developed a novel (to the best of our knowledge) dual-side view OCT (DSV-OCT) system for thickness measurement on opaque materials. The dual-side view was achieved on a conventional swept source OCT platform by creating two symmetrical sampling arms. This allows us to image both sides of the material simultaneously and produce the surface contours of the two sides in a single C scan. Finally, the thickness of the opaque material can be calculated from the two surface contours above. We demonstrated that our DSV-OCT technique can measure the thickness of opaque material with an accuracy of about 3 µm.

Opposing roles of miR-294 and MBNL1/2 in shaping the gene regulatory network of embryonic stem cells.

Alternative pre-mRNA splicing plays important roles in regulating self-renewal and differentiation of embryonic stem cells (ESCs). However, how specific alternative splicing programs are established in ESCs remains elusive. Here, we show that a subset of alternative splicing events in ESCs is dependent on miR-294 expression. Remarkably, roughly 60% of these splicing events are affected by the depletion of Muscleblind-Like Splicing Regulator 1 and 2 (Mbnl1/2). Distinct from canonical miRNA function, miR-294 represses Mbnl1/2 through both posttranscriptional and epigenetic mechanisms. Furthermore, we uncover non-canonical functions of MBNL proteins that bind and promote the expression of miR-294 targets, including Cdkn1a and Tgfbr2, thereby opposing the role of miR-294 in regulating cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Our study reveals extensive interactions between miRNAs and splicing factors, highlighting their roles in regulating cell type-specific alternative splicing and defining gene expression programs during development and cellular differentiation.

miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency.

Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8-/- mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming. Mechanistically, we identified Mbd2, a reader for methylated CpGs, as the target of miR-290 cluster that represses glycolysis and reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371 cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the reprogramming of human fibroblasts. Hence, we identified a previously unappreciated mechanism by which miR-290/371 miRNAs orchestrate epigenetic, transcriptional and metabolic networks to promote pluripotency in PSCs and during reprogramming.

Use of capillary electrophoresis to select a DNA aptamer that recognizes swine anaphylatoxin C5a.

Complement factor 5a is a potent proinflammatory mediator that contributes to the pathogenesis of numerous inflammatory diseases. Protein-based C5a inhibitors have proven to be clinically valuable. Aptamers, which are oligonucleic acid chains or polypeptides, can bind to target molecules and hence have the potential to be used for detection and blockade of targets. Here, we describe the discovery that the single-stranded DNA aptamer S1 can bind specifically to swine C5a, which can then be quickly selected for with capillary electrophoresis for high-throughput sequencing. Aptamer S1 bound specifically to swine C5a with a dissociation constant of 4 µM as measured by surface plasmon resonance (SPR). Moreover, aptamer S1 inhibited C5a-induced chemotaxis of neutrophils in vitro. Our study suggests that the S1 aptamer has great potential to be a key structure in the development of effective therapeutic agents against inflammatory diseases.

Functional Dissection of pri-miR-290~295 in Dgcr8 Knockout Mouse Embryonic Stem Cells.

The DiGeorge syndrome critical region gene 8 (Dgcr8) knockout strategy has been widely used to study the function of canonical microRNAs (miRNAs) in vitro and in vivo. However, primary miRNA (pri-miRNA) transcripts are accumulated in Dgcr8 knockout cells due to interrupted processing. Whether abnormally accumulated pri-miRNAs have any function is unknown. Here, using clustered regularly interspaced short palindromic repeats system/CRISPR-associated protein 9 (CRISPR/Cas9), we successfully knocked out the primary microRNA-290~295 (pri-miR-290~295) cluster, the most highly expressed miRNA cluster in mouse embryonic stem cells (ESCs), in Dgcr8 knockout background. We found that the major defects associated with Dgcr8 knockout in mouse ESCs, including higher expression of epithelial-to-mesenchymal transition (EMT) markers, slower proliferation, G1 accumulation, and defects in silencing self-renewal, were not affected by the deletion of pri-miR-290~290 cluster. Interestingly, the transcription of neighboring gene nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 12(Nlrp12) was upregulated upon the deletion of the pri-miR-290~295 cluster. Together, our results suggested that the major defects in Dgcr8 knockout ESCs were not due to the accumulation of pri-miR-290~295, and the deletion of miRNA genes could affect the transcription of neighboring DNA elements.

Intuitive Label-Free SERS Detection of Bacteria Using Aptamer-Based in Situ Silver Nanoparticles Synthesis.

The characteristic of an ideal bacteria-detection method should have high sensitivity and specificity, be easy to operate, and not have a time-consuming culture process. In this study, we report a new bacteria-detection strategy that can recognize bacteria quickly and directly by surface-enhanced Raman scattering (SERS) with the formation of well-defined bacteria-aptamer@AgNPs. SERS signals generated by bacteria-aptamer@AgNPs exhibited a linear dependence on bacteria (R2 = 0.9671) concentration ranging from 101 to 107 cfu/mL. The detection limit is sensitive down to 1.5 cfu/mL. Meanwhile, the bacteria SERS signal was dramatically enhanced by its specifically recognized aptamer, and the bacteria could be identified directly and visually through the SERS spectrum. This strategy eliminates the puzzling data analysis of previous studies and offers significant advantages over existing approaches, getting a critical step toward the creation of SERS-based biochips for rapid in situ bacteria detection in mixture samples.

Small Moving Vehicle Detection in a Satellite Video of an Urban Area.

Vehicle surveillance of a wide area allows us to learn much about the daily activities and traffic information. With the rapid development of remote sensing, satellite video has become an important data source for vehicle detection, which provides a broader field of surveillance. The achieved work generally focuses on aerial video with moderately-sized objects based on feature extraction. However, the moving vehicles in satellite video imagery range from just a few pixels to dozens of pixels and exhibit low contrast with respect to the background, which makes it hard to get available appearance or shape information. In this paper, we look into the problem of moving vehicle detection in satellite imagery. To the best of our knowledge, it is the first time to deal with moving vehicle detection from satellite videos. Our approach consists of two stages: first, through foreground motion segmentation and trajectory accumulation, the scene motion heat map is dynamically built. Following this, a novel saliency based background model which intensifies moving objects is presented to segment the vehicles in the hot regions. Qualitative and quantitative experiments on sequence from a recent Skybox satellite video dataset demonstrates that our approach achieves a high detection rate and low false alarm simultaneously.

A Rechargeable Al/S Battery with an Ionic-Liquid Electrolyte.

Aluminum metal is a promising anode material for next generation rechargeable batteries owing to its abundance, potentially dendrite-free deposition, and high capacity. The rechargeable aluminum/sulfur (Al/S) battery is of great interest owing to its high energy density (1340 Wh kg(-1) ) and low cost. However, Al/S chemistry suffers poor reversibility owing to the difficulty of oxidizing AlSx . Herein, we demonstrate the first reversible Al/S battery in ionic-liquid electrolyte with an activated carbon cloth/sulfur composite cathode. Electrochemical, spectroscopic, and microscopic results suggest that sulfur undergoes a solid-state conversion reaction in the electrolyte. Kinetics analysis identifies that the slow solid-state sulfur conversion reaction causes large voltage hysteresis and limits the energy efficiency of the system.

Feasibility of using 8 mL of iodinated contrast media in cerebral computed tomographic angiography with a dual-layer spectral detector.

Background: Virtual monoenergetic images (VMIs) at a low energy level can improve image quality when the amount of iodinated contrast media (CM) is reduced. The purpose was to evaluate the feasibility of using an extremely low CM volume and injection rate in cerebral computed tomography angiography (CTA) on a dual-layer spectral detector computed tomography (CT). Methods: Patients who were clinically suspected of intracranial aneurysm or cerebrovascular diseases were included in our study (from June to November 2022). In this prospective study, 80 patients were randomly enrolled into group A (8 mL of CM with a 1-mL/s flow rate) or group B (40 mL of CM with 4-mL/s flow rate). The VMIs at 40-70 keV in group A and polychromatic conventional images in the 2 groups were reconstructed. CT attenuation, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were evaluated via the t-test or Mann-Whitney test (2 groups), while analysis of variance or Kruskal-Wallis test (multiple groups). Subjective image quality was assessed on a 5-point scale. Results: In group A, the subjective image quality score, CT attenuation, and CNR of the internal carotid artery (ICA) and middle cerebral artery (MCA) were the highest on VMIs at 40 keV. The image noise on VMIs at 40 keV was 5.08±0.84 Hounsfield units. The subjective image quality score, CT value of the ICA, MCA, and cerebral parenchyma on VMIs at 40 keV in group A were similar to those in group B (all P values >0.05). Compared to those in group B, the VMIs at 40 keV in group A demonstrated a significantly higher mean SNR and CNR of the ICA (mean SNR: 46.22±20.18 vs. 34.32±12.40, P=0.002; CNR: 55.47±13.43 vs. 46.18±12.30, P=0.002) and MCA [SNR: 13.66 (9.78, 20.29) vs. 9.99 (7.53, 14.00), P=0.003; CNR: 47.00±12.71 vs. 39.45±10.47, P=0.005]. Conclusions: Cerebral CTA on VMIs at 40 keV with 8 mL of CM and a 1-mL/s injection rate can provide diagnostic image quality.