Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis.

Radiotherapy resistance is a challenge for colorectal cancer (CRC) treatment. Circular RNAs (circRNAs) play vital roles in the occurrence and development of CRC. This study aimed to investigate the role of circ_0005615 in regulating the radiosensitivity of CRC. The levels of circ_0005615, microRNA-665 (miR-665), and notch receptor 1 (NOTCH1) were detected by quantitative real-time PCR or western blot. The radiosensitivity of CRC cells was assessed by colony formation assay. Cell viability, apoptosis, and colony formation were assessed by Cell Counting Kit-8 assay, flow cytometry, and colony formation assay. Cell migration and invasion were confirmed by transwell assay and scratch assay. The binding relationship between miR-665 and circ_0005615 or NOTCH1 was verified by dual-luciferase reporter assay. Xenograft assay was used to test the effect of circ_0005615 on radiosensitivity in vivo. circ_0005615 and NOTCH1 were up-regulated, and miR-665 was down-regulated in CRC tissues and cells. Radiation decreased circ_0005615 and NOTCH1 levels and increased miR-665 level. Knockdown of circ_0005615 enhanced radiosensitivity of CRC cells. Moreover, circ_0005615 sponged miR-665 to regulate the radioresistance of CRC cells. Besides, miR-665 targeted NOTCH1 to mediate the radiosensitivity of CRC cells. Furthermore, circ_0005615 depletion increased CRC radiosensitivity in vivo. circ_0005615 silencing elevated radiosensitivity of CRC by regulating miR-665/NOTCH1 axis.

Integrative epigenome profiling of 47XXY provides insights into whole genomic DNA hypermethylation and active chromatin accessibility.

Klinefelter syndrome (KS, 47XXY) is a disorder characterized by sex chromosomal aneuploidy, which may lead to changes in epigenetic regulations of gene expression. To define epigenetic architectures in 47XXY, we annotated DNA methylation in euploid males (46XY) and females (46XX), and 47XXY individuals using whole genome bisulfite sequencing (WGBS) and integrated chromatin accessbilty, and detected abnormal hypermethylation in 47XXY. Furthermore, we detected altered chromatin accessibility in 47XXY, in particular in chromosome X, using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) in cultured amniotic cells. Our results construct the whole genome-wide DNA methylation map in 47XXY, and provide new insights into the early epigenomic dysregulation resulting from an extra chromosome X in 47XXY.

Characterization of plasma exosomal microRNAs in responding to radiotherapy of human esophageal squamous cell carcinoma.

Radiotherapy is one of the main treatment methods for esophageal squamous cell carcinoma (ESCC). Previous research has shown that plasma exosomal microRNAs (miRNAs) can predict therapeutic outcome. In the present study, to identify potential exosomal miRNAs that respond to radiotherapy, plasma exosomal miRNAs from ESCC patients undergoing radiotherapy were isolated and sequenced. Upregulated and downregulated miRNAs were detected from patients pre­ and post­radiotherapy, and it was found that they play distinct roles in DNA damage process and endosomal mediated transport. Based on wound healing and Cell Counting Kit­8 assays in TE­1 human esophageal cancer cells, it was identified that representative miRNA miR­652 and miR­30a alter migration but not proliferation. The present findings identified differentially expressed miRNAs in responding to radiotherapy, and added a reference to explore non­invasive plasma biomarkers to evaluate therapeutic effects in ESCC.

Design of a Morphing Skin with Shape Memory Alloy Based on Equivalent Thermal Stress Approach.

Shape memory alloy (SMA) is one of the potential driving devices for morphing aircraft due to its advantages of pseudoelasticity, superelasticity, and shape memory effect. Precise and fast analysis of SMA has simultaneously become a key requirement for industrial applications. In this study, a user-defined material subroutine (UMAT) was implemented and successfully applied in a three-dimensional numerical simulation in ABAQUS based on the extended Boyd-Lagoudas model. In addition to the conventional detwinned martensite (Md) and austenite (A), twinned martensite (Mt) was also considered to model the practical transformation accurately. Then, the equivalent thermal strain approach was adopted to simplify the simulation complexity with UMAT. By resetting the thermal expansion coefficient, the thermal strain equivalent to the original phase transformation strain was generated. The approach was validated in two cases, showing consistent results with the extended Boyd-Lagoudas model and reduction in time consumption by 89.1%. Lastly, an active morphing skin integrating the single-range SMA and a stainless-steel plate was designed to realize two-way morphing. The calculated arc height variation of the skin was 3.74 mm with a relative error of 1.84% compared to the experimental result of 3.81 mm. The coupled use of UMAT and the equivalent thermal stress approach helped to reduce the challenge in modeling SMA.

Single-Cell Transcriptomics of Cultured Amniotic Fluid Cells Reveals Complex Gene Expression Alterations in Human Fetuses With Trisomy 18.

Trisomy 18, commonly known as Edwards syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed cultured amniotic fluid cells from two euploid and three trisomy 18 samples using single-cell transcriptomics. We identified 6 cell groups, which function in development of major tissues such as kidney, vasculature and smooth muscle, and display significant alterations in gene expression as detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11 and 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.

Risk factors for atrioventricular block after occlusion for perimembranous ventricular septal defect.

BACKGROUND: The risk factors for complete atrioventricular block (CAVB) after device closure of perimembranous ventricular septal defect (pmVSD) remain unclear. OBJECTIVE: The purpose of this study was to analyze the incidence and risk factors for CAVB after device closure for pmVSD. METHODS: We reviewed 1884 patients with pmVSD who had undergone successful device occlusion between June 2005 and January 2020. Permanent CAVB was defined as CAVB requiring implantation of a permanent pacemaker (PPM) or extraction of the occluder. RESULTS: In total, 14 patients (0.7%) developed permanent CAVB. Of these patients, 10 (0.5%) required PPM implantation. Four permanent CAVB occurred within 7 days after the procedure (acute), 2 between 7 and 30 days (subacute), 3 between 30 days and 1 year (late), and 5 more than 1 year (very late). None of the subacute, late, and very late CAVB recovered normal conduction with medication and eventually required device removal or PPM implantation. Four patients with acute CAVB and 1 with subacute CAVB underwent device removal, and 4 (80%) recovered normal conduction. Multivariate regression revealed that the ratio of device to defect size was the only independent risk factor for permanent CAVB (odds ratio 3.027; 95% confidence interval 1.476-6.209; P = .003). CONCLUSION: The incidences of permanent CAVB after occlusion for pmVSD and PPM implantation were 0.7% and 0.5%, respectively. The ratio of device to defect size was the only independent risk factor for permanent CAVB. Device removal is an effective therapeutic modality for recovering normal conduction in acute and subacute CAVB patients.

Interneuron origin and molecular diversity in the human fetal brain.

Precise generation of excitatory neurons and inhibitory interneurons is crucial for proper formation and function of neural circuits in the mammalian brain. Because of the size and complexity of the human brain, it is a challenge to reveal the rich diversity of interneurons. To decipher origin and diversity of interneurons in the human fetal subpallium, here we show molecular features of diverse subtypes of interneuron progenitors and precursors by conducting single-cell RNA sequencing and in situ sequencing. Interneuron precursors in the medial and lateral ganglionic eminence simultaneously procure temporal and spatial identity through expressing a combination of specific sets of RNA transcripts. Acquisition of various interneuron subtypes in adult human brains occurs even at fetal stages. Our study uncovers complex molecular signatures of interneuron progenitors and precursors in the human fetal subpallium and highlights the logic and programs in the origin and lineage specification of various interneurons.

Differential expression of microRNAs in the human fetal left and right cerebral cortex.

Human brain is anatomically and functionally asymmetric. How brain asymmetry is initiated and established during fetal development is poorly understood. Accumulating evidence has shown that microRNAs (miRNAs) play crucial roles in brain development and function. In this study, we investigate miRNA expression profiles in left and right hemispheres of human fetal brains at 12 weeks post conception (PC), and identify 42 miRNAs showing differential expression between two hemispheres using Affymetrix microarray analyses. Target genes for left- and right-biased miRNAs are largely involved in developmental and functional regulations in the cortex such as axon guidance, GABAergic synapse and dopaminergic synapse pathways. Moreover, we find that predicted targets associated with canonical and non-canonical WNT signaling pathway show variations and differential expression between two hemispheres in response to left- and right-biased miRNAs. Our results highlight a potential role of miRNAs in regulating asymmetric development of human fetal brains.

Outcomes of closure of doubly committed subarterial ventricular septal defects in adults.

BACKGROUND: Outcome data of doubly committed subarterial ventricular septal defect closure in adults are limited. METHODS: A review was made of the inpatients >18 years of age who underwent doubly committed subarterial ventricular septal defect closure between June 2010 and June 2017. RESULTS: The patients were categorised into two groups: The valve intervention group consisted of 31 patients who underwent aortic valvuloplasty, aortic valve replacement, or repair of sinus Valsalva aneurysm in addition to doubly committed subarterial ventricular septal defect closure; non-valvular intervention group comprised 58 patients who underwent only doubly committed subarterial ventricular septal defect closure. The groups did not differ by sex and age. Patients in the valve intervention group, with a larger ventricular septal defect size, were shorter and tended to be lighter. The valve intervention group had more patients with pneumonia perioperatively. No infective endocarditis and reoperation were noted during the study period. At last follow-up, 91 and 96.6% of the studied patients were free from left ventricle dilation and pulmonary hypertension. In patients without pre-operative aortic regurgitation, 12 developed new mild aortic regurgitation during the follow-up. CONCLUSIONS: About 34.8% of adult patients with doubly committed subarterial ventricular septal defect required concurrent intervention on aortic valve or sinus Valsalva aneurysm. The midterm results of doubly committed subarterial ventricular septal defect closure in adult patients were favourable. However, the incidence of new mild aortic regurgitation after ventricular septal defect closure was high (27.3%). Long-term follow-up of aortic regurgitation progression is needed.

Transthoracic echocardiography as an alternative major guidance to angiography during transcatheter closure of patent ductus arteriosus: technical feasibility and clinical relevance.

The conventional transcatheter closure of patent ductus arteriosus (PDA) requires femoral artery puncture and angiography for duct anatomic and shunting estimation. If such estimation can be replaced by transthoracic echocardiography (TTE), the procedure will be further simplified, with fewer invasions. This study aimed to examine whether TTE can serve as an alternative to aorta angiography and as a major guidance for transcatheter duct closure. The study enrolled 298 consecutive patients (71 males and 227 females) with PDA. In the study, TTE with combined two-dimensional echocardiography (2DE) imaging and color-coded flow imaging (CDFI) was performed to measure the minimal shunting width (MSW) as the estimated minimal duct size for selection of an Amplatzer duct occluder (ADO) and to monitor the transcatheter duct closure intraprocedurally. The MSW was validated against the duct-stretched diameter (SDD), against the minimal waist diameter of the conical part of a released occluder measured by X-ray spot picture after successful duct closure (SDC), and against the size of the finally used ADO (SADO). Good correlation was found between MSW and SDD [SDD (mm) = 1.31 MSW; r = 0.89; p < 0.01] and between MSW and SADO [SADO (mm) = 1.71 MSW; r = 0.88; p < 0.01]. Of 296 patients who received occlusion using MSW as the reference for selection of the occluder, SDC was attained in 288 (97.3%), 5 (1.7%), and 2 (0.7%) patients, respectively, at the first, second (1 ADO replacement), and third (2 ADO replacements) occluding attempt. Acute occluder dislodgement occurred in one patient (0.3%). At the 12-month follow-up assessment, no major complications were found, and the total immediate or 12-month SDC was 99.7%. Echocardiography as an alternative major guidance to angiography for transcatheter duct closure is technically feasible, and TTE guidance can further simplify the procedure, with fewer invasions and potential complications.

ERCC1 single nucleotide polymorphism C8092A, but not its expression is associated with survival of esophageal squamous cell carcinoma patients from Fujian province, China.

Esophageal carcinoma is one of the world's deadliest cancers. Esophageal squamous cell carcinoma (ESCC) is more frequent than adenocarcenoma (AC) in China. Platinum-based chemotherapy with surgical resection is a common treatment approach for ESCC; however, the treatment response is uncertain. Evidence suggests polymorphisms in genes encoding excision repair cross-complementing group 1 (ERCC1), a protein involved in nuclear excision repair (NER), may help predict response to cisplatin and other platinum-based chemotherapeutics. Multiple ERCC1 single nucleotide polymorphisms (SNPs) have been associated with platinum chemotherapy response. Two common SNPs occur at the C8092A and C118T loci. Our study aimed to determine if 1) an association exists between ERCC1 tumor expression and patient survival, 2) whether adjuvant therapy influence on survival is related to histological ERCC1 presence in tumor cell nuclei, and 3) whether other clinicopathological characteristics in a cohort of patients following surgery for various stages of ESCC are associated with tumor ERCC1 expression. One hundred eight patients were included in the study, and tumor biopsy was collected for genotyping and immunohistochemical analysis of ERCC1. Sixty-seven patients (62%) received no adjuvant therapy, and the rest had either platinum-based chemotherapy (28.5%), radiotherapy (6.5%) or both treatments (2.8%). Log-rank analysis revealed no significant connection between tumor ERCC1 expression (P = 0.12) or adjuvant therapy (P = 0.56) on patient survival. Also, non-parametric Mann-Whitney analysis showed no significant link between tumor size or nodus tumor formation and ERCC1 presence in patients in the study. Interestingly, C8092A SNP showed significant association with patient survival (P = 0.01), with patients homozygous for the mutant allele showing the most significantly reduced survival (P = 0.04) compared to those homozygous for the dominant allele (CC). Our results provide novel insight into the genotypic variation of patients from Quanzhou, Fujian province China.

Synthesis, DNA-binding, and photocleavage properties of a serious of porphyrin-daunomycin hybrids.

It is widely accepted that the pharmacological activities of anthracyclines antitumor agents express when the quinone-containing chromophore intercalates into base pairs of the duplex DNA. We have successfully synthesized and investigated the DNA-interactions of hybrids composed with quinone chromophore and cationic porphyrin. Herein, a clinic anticancer drug, daunomycin, is introduced to the porphyrin hybrids through different lengths of amide alkyl linkages, and their interactions and cleavage to DNA were studied compared with the previous porphyrin-quinone hybrids. Spectral results and the determined binding affinity constants (Kb) show that the attachment of daunomycin to porphyrin could improve the DNA-binding and photocleaving abilities. The porphyrin-daunomycin hybrids may find useful employment in investigating the ligand-DNA interaction.

Simultaneous determination of cadmium (II) and lead (II) with clay nanoparticles and anthraquinone complexly modified glassy carbon electrode.

An anthraquinone (AQ) improved Na-montmorillonite nanoparticles (nano-SWy-2) chemically modified electrode (CME) has been developed for the simultaneous determination of trace levels of cadmium (II) and lead (II) by differential pulse anodic stripping voltammetry (DPASV). This method is based on a non-electrolytic preconcentration via ion exchange model, followed by an accumulation period via the complex formation in the reduction stage at -1.2V, and then by an anodic stripping process. The mechanism of this design was proposed and the analytical performance was evaluated with several variables. Under the optimized working conditions, the detection limit was 3 and 1nM for Cd(2+) and Pb(2+), respectively. The calibration graphs were linear in the concentration ranges of 8x10(-9) to 1x10(-6)molL(-1) (Cd(2+)) and of 2x10(-9) to 1x10(-6)molL(-1) (Pb(2+)). Many inorganic species did not interfere with the assay significantly; the high sensitivity, selectivity, and stability of this nano-SWy-2-AQ CME were demonstrated. The applications for the detection of trace levels of Cd(2+) and Pb(2+) in milk powder and lake water samples indicate that it is an economical and potent method.