Enhancers are important regulatory elements that can control gene activity across vast genetic distances. However, the underlying nature of this regulation remains obscured because it has been ...difficult to observe in living cells. Here, we visualize the spatial organization and transcriptional output of the key pluripotency regulator
and its essential enhancer
Control Region (SCR) in living embryonic stem cells (ESCs). We find that
and SCR show no evidence of enhanced spatial proximity and that spatial dynamics of this pair is limited over tens of minutes.
transcription occurs in short, intermittent bursts in ESCs and, intriguingly, we find this activity demonstrates no association with enhancer proximity, suggesting that direct enhancer-promoter contacts do not drive contemporaneous
transcription. Our study establishes a framework for interrogation of enhancer function in living cells and supports an unexpected mechanism for enhancer control of
expression that uncouples transcription from enhancer proximity.
Mutations in gene regulatory elements have been associated with a wide range of complex neuropsychiatric disorders. However, due to their cell-type specificity and difficulties in characterizing ...their regulatory targets, the ability to identify causal genetic variants has remained limited. To address these constraints, we perform an integrative analysis of chromatin interactions, open chromatin regions and transcriptomes using promoter capture Hi-C, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing, respectively, in four functionally distinct neural cell types: induced pluripotent stem cell (iPSC)-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus-like neurons and primary astrocytes. We identify hundreds of thousands of long-range cis-interactions between promoters and distal promoter-interacting regions, enabling us to link regulatory elements to their target genes and reveal putative processes that are dysregulated in disease. Finally, we validate several promoter-interacting regions by using clustered regularly interspaced short palindromic repeats (CRISPR) techniques in human excitatory neurons, demonstrating that CDK5RAP3, STRAP and DRD2 are transcriptionally regulated by physically linked enhancers.
•The HPF-LADRC is introduced to replace the traditional PI controller on the wind turbine's rotor side converter. Firstly, the estimate and feedback of the system's subsynchronous oscillations are ...implemented using linear extended state observer (LESO) in the LADRC.•An HPF is added to the linear state error feedback (LSEF) in the LADRC to mitigate low-frequency oscillation.•Time-domain simulations and impedance model-based analysis are performed to validate the proposed suppression technique for SSCI under different wind speeds, compensated levels, and the number of in-service DFIGs.
Doubly-fed induction generator (DFIG)-based wind farms interact with series capacitors in transmission lines, leading to sub-synchronous control interaction (SSCI). The SSCI's oscillation frequency is affected by the system's operating conditions. Therefore, this paper proposes the linear active disturbance rejection control (LADRC) based on the high-pass filter (HPF) to mitigate SSCI under various conditions. The HPF-LADRC is introduced to replace the traditional PI controller on the wind turbine's rotor side converter. Firstly, the estimate and feedback of the system's subsynchronous oscillations are implemented using linear extended state observer (LESO) in the LADRC. Then, an HPF is added to the linear state error feedback (LSEF) in the LADRC to mitigate low-frequency oscillation. Finally, time-domain simulations and impedance model-based analysis are performed to validate the proposed suppression technique for SSCI under different wind speeds, compensated levels, and the number of in-service DFIGs. The results demonstrate that the proposed HPF-LADRC increases the system's low-frequency band dampness and enhances its disturbance resistance.
Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using ...single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone
. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.
Freezing is a serious problem that affects the power, transport, and transmission industries and is a major concern for the national economy and safety. Currently, several engineering de-icing ...methods, such as thermal, mechanical, and chemical de-icing, have shown problems related to energy consumption, efficiency, and the environment. Superhydrophobic materials have high droplet contact and roll angles, which can reduce the droplet residence and ice adhesion on their surfaces and have unique advantages in the self-cleaning and anti-icing fields. This paper introduces the development of infiltration theory and superhydrophobic materials and their principles of anti-icing and de-icing. Herein, the preparation and coating methods of superhydrophobic materials in applications are summarised, the performance and lifetime issues of superhydrophobic materials in applications are clarified, and the research progress on superhydrophobic materials in different fields is reviewed. Prospects for the application of superhydrophobic materials in electrified railways are also presented. A feasibility study was conducted to solve some of the existing problems of electrified railways, providing a theoretical basis for the development of electrified railways.
Superhydrophobic coatings give a solution for the protection of electrical equipment and some corresponding preparation methods.
Soil contamination with toxic heavy metals such as arsenic (As) is becoming a serious global problem because of the rapid development of the social economy. Although plant growth-promoting bacteria ...(PGPB) and nanoparticles (NPs) are the major protectants to alleviate metal toxicity, the study of these chemicals in combination to ameliorate the toxic effects of As is limited. Therefore, the present study was conducted to investigate the combined effects of different levels of
(5 ppm and 10 ppm) and iron oxide nanoparticles (FeO-NPs) (50 mg/l
and 100 mg/l
) on plant growth and biomass, photosynthetic pigments, gas exchange attributes, oxidative stress and response of antioxidant compounds (enzymatic and non-enzymatic), and their specific gene expression, sugars, nutritional status of the plant, organic acid exudation pattern As accumulation from the different parts of the plants, and electron microscopy under the soil, which was spiked with different levels of As 0 μM (i.e., no As), 50 μM, and 100 μM in Ajwain (
L.) seedlings. Results from the present study showed that the increasing levels of As in the soil significantly (
< 0.05) decreased plant growth and biomass, photosynthetic pigments, gas exchange attributes, sugars, and nutritional contents from the roots and shoots of the plants, and destroyed the ultra-structure of membrane-bound organelles. In contrast, increasing levels of As in the soil significantly (
< 0.05) increased oxidative stress indicators in term of malondialdehyde, hydrogen peroxide, and electrolyte leakage, and also increased organic acid exudation patter in the roots of
.
seedlings. The negative impact of As toxicity can overcome the application of PGPB (
) and FeO-NPs, which ultimately increased plant growth and biomass by capturing the reactive oxygen species, and decreased oxidative stress in
.
seedlings by decreasing the As contents in the roots and shoots of the plants. Our results also showed that the FeO-NPs were more sever and showed better results when we compared with PGPB (
) under the same treatment of As in the soil. Research findings, therefore, suggest that the combined application of
and FeO-NPs can ameliorate As toxicity in
.
seedlings, resulting in improved plant growth and composition under metal stress, as depicted by balanced exudation of organic acids.
The development of economic catalysts for aerobic oxidation procedure has attracted extensive attention. In this work, a novel Ni/Zn supported defective carbon with multi-functional catalytic sites ...was fabricated via a two-step pyrolysis-H
2
O
2
treatment. The catalyst was applied to the Baeyer–Villiger (B–V) oxidation using ambient air as a green and safe oxidant. The catalyst with optimal Ni/Zn ratio of (2:1) delivers a high catalytic activity (> 92%) and perfect selectivity (> 99%) for the conversion of a wide range of substituted cyclic-ketones to the corresponding lactones. The characterization results have clarified that the H
2
O
2
treatment leads to the formation of active N/O-group on the catalyst surface, which facilitates the adsorption of substrate/intermediate molecules and benefits the reaction. Moreover, the synergistic effect between multi-functional sites results in the buffering/stabilizing of free radicals, enhanced efficiency of oxygen insertion to form lactone. The design principle in this work is believed to shed light on the exploration of all-in-one solid catalyst for diverse oxidative reaction.
Graphical Abstract
Objective
In recent years, the Emergency Care Research Institute has advised that endoscope cleaning is of considerable importance. In the present study, a quality control circle (QCC) was used to ...reduce the formation of biofilms in flexible endoscopes within one hospital in Guangdong Province, China.
Methods
During reprocessing of 235 flexible endoscopes in the urology surgical suite, adenosine triphosphate (ATP) detection was used to monitor the efficacy of biofilm removal. The internal and external parts of flexible endoscopes were used as sampling sites by means of the flushing and smudge methods, respectively. When the two results reached the standard of less than 500 relative light units/piece at the same time, endoscopic biofilm clearance was considered to be qualified. A QCC was established to implement a 10-step plan-do-check-act model.
Results
The baseline qualified rate (i.e., ATP monitoring pass rate) during reprocessing of 235 flexible endoscopes was 50%. During the study, the qualified rate increased to 85.29% after establishment of the QCC. During reprocessing of 150 flexible endoscopes in the following 6 months, the qualified rate remained at 90%.
Conclusion
Establishment of the QCC improved the removal of biofilm from flexible endoscopes in the urology surgical suite.
Objective
This study aimed to compare the therapeutic effect of intravesical instillation hyaluronic acid with intradetrusor botulinum toxin A (BTX-A) injection or cystoscopic hydrodistention for ...ketamine-associated cystitis.
Methods
Thirty-six patients were evenly randomly divided into the BTX-A group or the hydrodistention group. Patients received 200 U BTX-A detrusor injections in the BTX-A group and cystoscopic hydrodistention in the hydrodistention group. Intravesical instillation of hyaluronic acid was administrated in both groups for eight times. Patients with involuntary detrusor contraction were divided into the persistent involuntary detrusor contraction group and resolved involuntary detrusor contraction group after treatment in 6 months. The predictors of persistent involuntary detrusor contraction were analyzed.
Results
Twelve months after treatment, the daytime frequency, Interstitial Cystitis Symptom Index, maximal capacity, and maximal cystometric capacity in the BTX-A group were significantly better than those in the hydrodistention group. Patients with resolution of involuntary detrusor contraction had a significantly shorter duration of ketamine, lower amount of fibrosis in pathology, and higher maximal capacity than those with persistent involuntary detrusor contraction 6 months after therapy.
Conclusion
Intravesical instillation of hyaluronic acid with intradetrusor BTX-A injection appears to be a preferable option for long-term effectiveness compared with cystoscopic hydrodistention.
Prostate cancer (PCa) is a high morbidity malignancy in males, and biochemical recurrence (BCR) may appear after the surgery. Our study is designed to build up a risk score model using circular RNA ...sequencing data for PCa. The dataset is from the GEO database, using a cohort of 144 patients in Canada. We removed the low abundance circRNAs (FPKM < 1) and obtained 546 circRNAs for the next step. BCR-related circRNAs were selected by Logistic regression using the "survival" and "survminer" R package. Least absolute shrinkage and selector operation (LASSO) regression with 10-fold cross-validation and penalty was used to construct a risk score model by "glmnet" R software package. In total, eight circRNAs (including circ_30029, circ_117300, circ_176436, circ_112897, circ_112897, circ_178252, circ_115617, circ_14736, and circ_17720) were involved in our risk score model. Further, we employed differentially expressed mRNAs between high and low risk score groups. The following Gene Ontology (GO) analysis were visualized by Omicshare Online tools. As per the GO analysis results, tumor immune microenvironment related pathways are significantly enriched. "CIBERSORT" and "ESTIMATE" R package were used to detect tumor-infiltrating immune cells and compare the level of microenvironment scores between high and low risk score groups. What's more, we verified two of eight circRNA's (circ_14736 and circ_17720) circular characteristics and tested their biological function with qPCR and CCK8
. circ_14736 and circ_17720 were detected in exosomes of PCa patients' plasma. This is the first bioinformatics study to establish a prognosis model for prostate cancer using circRNA. These circRNAs were associated with CD8
T cell activities and may serve as a circRNA-based liquid biopsy panel for disease prognosis.
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