CircABCA13 acts as a miR-4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1.

Circular RNAs (circRNAs) play a pivotal role in the tumorigenesis and progression of various cancers. However, the role and mechanisms of circABCA13 in esophageal squamous cell carcinoma (ESCC) are largely unknown. Here, we reported that circABCA13, a novel circular RNA generated by back-splicing of the intron of the ABCA13 gene, is highly expressed in ESCC tumor tissues and cell lines. Upregulation of circABCA13 correlated with TNM stage and a poor prognosis in ESCC patients. While knockdown of circABCA13 in ESCC cells significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth, overexpression of circABCA13 facilitated tumor growth both in vitro and in vivo. In addition, circABCA13 directly binds to miR-4429 and sequesters miR-4429 from its endogenous target, SRXN1 mRNA, which subsequently upregulates SRXN1 and promotes ESCC progression. Consistently, overexpression of miR-4429 or knockdown of SRXN1 abolished malignant behavior promotion of ESCC results from circABCA13 overexpression in vitro and in vivo. Collectively, our study uncovered the oncogenic role of circABCA13 and its mechanism in ESCC, suggesting that circABCA13 could be a potential therapeutic target and a predictive biomarker for ESCC patients.

Circular RNA circ-FIRRE interacts with HNRNPC to promote esophageal squamous cell carcinoma progression by stabilizing GLI2 mRNA.

Increasing evidence has shown that circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) and promote cancer progression. However, the function and mechanism of the circRNA/RBP complex in esophageal squamous cell carcinoma (ESCC) are still largely unknown. Herein, we first characterized a novel oncogenic circRNA, circ-FIRRE, by RNA sequencing (Ribo-free) profiling of ESCC samples. Furthermore, we observed marked circ-FIRRE overexpression in ESCC patients with high TNM stage and poor overall survival. Mechanistic studies indicated that circ-FIRRE, as a platform, interacts with the heterogeneous nuclear ribonucleoprotein C (HNRNPC) protein to stabilize GLI2 mRNA by directly binding to its 3'-UTR in the cytoplasm, thereby resulting in elevated GLI2 protein expression and subsequent transcription of its target genes MYC, CCNE1, and CCNE2, ultimately contributing to ESCC progression. Moreover, HNRNPC overexpression in circ-FIRRE knockdown cells notably abolished circ-FIRRE knockdown-mediated Hedgehog pathway inhibition and ESCC progression impairment in vitro and in vivo. Clinical specimen results showed that circ-FIRRE and HNRNPC expression was positively correlated with GLI2 expression, which reveals the clear significance of the circ-FIRRE/HNRNPC-GLI2 axis in ESCC. In summary, our results indicate that circ-FIRRE could serve as a valuable biomarker and potential therapeutic target for ESCC and highlight a novel mechanism of the circ-FIRRE/HNRNPC complex in ESCC progression regulation.

Circ_16601 facilitates Hippo pathway signaling via the miR-5580-5p/FGB axis to promote my-CAF recruitment in the TME and LUAD progression.

BACKGROUND: Lung cancer represents a significant public health issue in China, given its high incidence and mortality rates. Circular RNAs (circRNAs) have been recently proposed to participate in the development and progression of tumors. Nevertheless, their particular roles in the pathogenesis of lung adenocarcinoma (LUAD), the tumor microenvironment (TME), and the underlying molecular mechanisms are still not well understood. METHODS: High-throughput sequencing was used to analyze the circRNAs expression profiles in 7 pairs of human LUAD tissues. shRNA was used to knockdown the YAP1 and FGB genes. RNA sequencing and RT-qPCR were performed to classify the regulatory effects of circ_16601 in LUAD cells. The progression effect of circ_16601 on lung cancer was investigated in vitro and in vivo. RESULTS: The circ_16601 is significantly elevated in LUAD tissues compared to adjacent normal lung tissues, and its high expression is positively associated with poor prognosis in LUAD patients. Additionally, circ_16601 overexpression promotes LUAD cell proliferation in vitro and increases xenograft tissue growth in mice in vivo; circ_16601 also could recruit fibroblasts to cancer associate fibroblasts. Mechanistically, circ_16601 can directly bind to miR-5580-5p, preventing its ability to degrade FGB mRNA and enhancing its stability. Subsequently, circ_16601 promotes the activation of the Hippo pathway in a YAP1-dependent manner, leading to LUAD progression. CONCLUSIONS: Our findings shed valuable insights into the regulatory role of circ_16601 in LUAD progression and highlight its potential as a diagnostic and therapeutic target in LUAD. Overall, this study provides theoretical support to improve the prognosis and quality of life of patients suffering from this devastating disease.

A dual-responsive colorimetric probe for the detection of Cu2+ and Ni2+ species in real water samples and human serum.

The monitoring of heavy transition metals has increasingly attracted great attention because they pollute the environment and have unique physiological functions. Chemosensors are useful tools for monitoring heavy transition metals due to their simple visualization, excellent sensitivity and high selectivity. Herein, we have developed a novel chemosensor for the detection of water-soluble Cu2+ and Ni2+ species with different mechanisms, and low detection limits of 2.1 nM for Cu2+ and 1.2 nM for Ni2+ were obtained. The colorimetric probe CPH has been applied to qualitative and quantitative detection of Cu2+ and Ni2+ species in real samples.

[Pyrexia and hemoptysis for eight days in a school-age child].

A girl was diagnosed with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) due to pyrexia and hemoptysis for eight days. The girl was a school-age child with major clinical manifestations of pyrexia, skin rash, enlargement of bilateral cervical lymph nodes, conjunctival hyperaemia, red and cracked lips and strawberry-like tongue, followed by swelling of both hands and feet. Laboratory examination showed significant increases in white blood cell count, platelet count, C-reactive protein, erythrocyte sedimentation rate and liver enzymes, a significant reduction in albumin, and the presence of aseptic pyuria. After the first course of IVIG treatment, the girl still had recurrent pyrexia, with hemoptysis on day 2 after admission, and lung CT showed uneven luminance and patchy shadow. The symptoms were quickly alleviated after the second course of IVIG treatment combined with methylprednisolone and aspirin treatment. KD is a febrile disease characterized by multiple systemic vasculitis in childhood and can involve various organ systems such as the heart, lungs, kidneys and the nervous system. Therefore, it is necessary to carefully monitor and recognize the rare symptoms of KD, and early recognition of pulmonary complications of KD can avoid delay in diagnosis, prevent the development of more serious complications, and help with early treatment and disease recovery.

Interleukin-1ß Plays a Pivotal Role via the PI3K/Akt/mTOR Signaling Pathway in the Chronicity of Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy. It is often associated with hippocampal sclerosis, which is histopathologically characterized by selective neuron loss, mossy fiber sprouting, and synapse reconstruction, and is the primary cause of refractory epilepsy. Its mechanism has not been fully elucidated. Substantial evidence now supports that inflammatory pathways are activated in epilepsy foci. We have confirmed that the interleukin-1ß (IL-1ß) level is involved in the epileptogenesis of MTLE, and we further investigated how it works in its chronicity in this study. METHODS: The MTLE model was induced by pilocarpine, and Western blot and co-immunoprecipitation were used to detect proteins related to the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway in the hippocampi of MTLE rats and MTLE children. Meanwhile, primary hippocampal neurons were cultured and transfected by lentivirus, and the same methods were used to test the related protein expression; fluorescent dye FM4-64 was used to measure synaptic vesicle endocytosis (SVE) of neurons. RESULTS: We revealed that mTOR is continuously activated in the rat MTLE model and children with MTLE, and it correlated with the IL-1ß level. We further proved that IL-1ß activates neurons via the PI3K/Akt/mTOR signaling pathway, accompanied by the upregulation of MAP2 and the enhancement of SVE in hippocampal neurons. CONCLUSION: Our findings suggest that IL-1ß can activate mTOR, followed by activated neurons, which is critical in the pathogenesis of MTLE chronicity. These findings contribute to the understanding of the pathogenesis of MTLE, and targeting inflammation modulators in MTLE may provide new pathways for therapy of refractory epilepsy.

Does overconfident CEO lead to corporate environmental misconducts? Evidence from China.

Enterprises are drawing growing criticism for violating environmental rules. The research examines whether and how top executives' mental bias leads to corporate environmental misconduct (CEI). Drawing on upper echelon theory (UET) and agency theory, we link CEO overconfidence with CEI, and explore the boundary conditions from the perspective of management discretion at the governance level. Using a data set covering the Chinese listed enterprises from 2004 to 2016, the empirical results demonstrate that CEO overconfidence positively and markedly influenced CEI. Moreover, shareholder concentration and CEO duality reinforce the relationship between overconfidence and CEI, whereas board independence is the opposite. The findings clarify ecological outcomes of CEO overconfidence and have remarkable significance in theory and practice.

miR-493-5p Silenced by DNA Methylation Promotes Angiogenesis via Exosomes and VEGF-A-Mediated Intracellular Cross-Talk Between ESCC Cells and HUVECs.

Background: Exosomal microRNAs (miRNAs) in the tumor microenvironment play crucial roles in tumorigenesis and tumor progression by participating in intercellular cross-talk. However, the functions of exosomal miRNAs and the mechanisms by which they regulate esophageal squamous cell carcinoma (ESCC) progression are unclear. Methods: RNA sequencing and GEO analysis were conducted to identify candidate exosomal miRNAs involved in ESCC development. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of plasma exosomal miR-493-5p. EdU, tube formation and Transwell assays were used to investigate the effects of exosomal miR-493-5p on human umbilical vein endothelial cells (HUVECs). A subcutaneous xenograft model was used to evaluate the antitumor effects of miR-493-5p and decitabine (a DNA methyltransferase inhibitor). The relationship between miR-493-5p and SP1/SP3 was revealed via a dual-luciferase reporter assay. A series of rescue assays were subsequently performed to investigate whether SP1/SP3 participate in exosomal miR-493-5p-mediated ESCC angiogenesis. Results: We found that miR-493-5p expression was notably reduced in the plasma exosomes of ESCC patients, which showed the high potential value in early ESCC diagnosis. Additionally, miR-493-5p, as a candidate tumor suppressor, inhibited the proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGFA and exerted its angiostatic effect via exosomes. Moreover, we found that SP1/SP3 are direct targets of miR-493-5p and that re-expression of SP1/SP3 could reverse the inhibitory effects of miR-493-5p. Further investigation revealed that miR-493-5p expression could be regulated by DNA methyltransferase 3A (DNMT3A) and DNMT3B, and either miR-493-5p overexpression or restoration of miR-493-5p expression with decitabine increased the antitumor effects of bevacizumab. Conclusion: Exosomal miR-493-5p is a highly valuable ESCC diagnosis marker and inhibits ESCC-associated angiogenesis. miR-493-5p can be silenced via DNA methylation, and restoration of miR-493-5p expression with decitabine increases the antitumor effects of bevacizumab, suggesting its potential as a therapeutic target for ESCC treatment.

[Comorbidities and functional impairments in children with attention deficit hyperactivity disorder].

OBJECTIVE: To assess comorbidities and functional impairments in children with attention deficit hyperactivity disorder (ADHD), and to investigate their relationship with the core symptoms (attention deficit and hyperactivity) of ADHD. METHODS: A total of 319 children with suspected ADHD were included in the study. The Vanderbilt ADHD Parent Rating Scale (VADPRS) was completed by their parents. Diagnosis and classification were performed based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Comorbidities and functional impairments were evaluated according to the VADPRS. Children with various types of ADHD were compared in terms of comorbidities and functional impairments, and their relationship with the core symptoms of ADHD was analyzed. RESULTS: Of the 319 children, 196 were diagnosed with ADHD, including 84 cases of predominantly inattentive type (ADHD-I), 35 cases of predominantly hyperactive-impulsive type (ADHD-HI) and 77 cases of combined type (ADHD-C); 123 did not meet the diagnostic criteria for ADHD. At least one other psychiatric disorder (oppositional defiant disorder, conduct disorder or emotional disorder) was seen in 63.8% (125/196) of the children with ADHD, versus 37.4 % (46/123) of the children without ADHD (P<0.05). The incidence of oppositional defiant disorder and conduct disorder in the ADHD-C subgroup was significantly higher than in the ADHD-I subgroup (P<0.05). The sums of oppositional defiant disorder, conduct disorder and emotional disorder symptoms were weakly correlated with the sums of hyperactive-impulsive and inattentive symptoms (P<0.01). Up to 89.8% of children with ADHD and 74.8% of children without ADHD showed functional impairments (P<0.05). The ADHD-C subgroup had a significantly higher overall incidence of functional impairments than the ADHD-I and ADHD-HI subgroups (P<0.05). The sum of inattentive symptoms was weakly correlated with the scores of learning ability, sibling relationship and participation in organized activities (P<0.01), and the sum of hyperactive-impulsive symptoms was weakly correlated with the score of sibling relationship (P<0.01). CONCLUSIONS: The incidence of comorbidities and functional impairments among children with ADHD is high, especially in those with ADHD-C. The severity of core symptoms in children with ADHD can influence the occurrence of comorbidities and functional impairments. The incidence of psychiatric disorders and functional impairments is also high in children with suspected ADHD who do not meet the diagnostic criteria for ADHD, so attention also needs to be paid to interventions among these children.