CircTENM3 inhibites tumor progression via the miR-558/RUNX3 axis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is currently acknowledged as the second most widespread cancer among men worldwide. Yet, the lack of dependable diagnostic biomarkers and therapeutic targets has presented considerable hurdles to the progression of prostate cancer treatment. Circular RNAs are implicated in the pathogenesis of numerous diseases, positioning them as promising biomarkers for diverse medical conditions. This study aims to uncover a specific circRNA that could serve as a diagnostic and therapeutic target for detecting and treating PCa. METHODS: The change of circTENM3 expression levels in PCa was detected by qPCR. CCK8 assays, EdU assays, Scratch assay and Transwell migration assay conducted to detect the role of circTENM3 in PCa cells in vitro. RIP assay, RNA-pull down and luciferase reporter assay were performed to explore the mechanism of circTENM3. Gain-of-function analysis was performed to reveal the function of circTENM3 in PCa in vivo. RESULTS: The results revealed that the expression level of circTENM3 was significantly down-regulated in PCa. CircTENM3 overexpression alleviated the progression of PCa in vitro. Mechanistically, circTENM3 enhanced RUNX3 levels via miR-558 sponge. Gain-of-function analysis determined that circTENM3 overexpression could inhibit PCa progression in vitro. CONCLUSIONS: Our research offers profound insights into the protective role played by circTENM3 in PCa. CircTENM3 operates as a sponge for miR-558, thereby triggering the elevation of RUNX3 expression, which subsequently curbs the progression of PCa.

Circ-MALAT1 accelerates cell proliferation and epithelial mesenchymal transformation of colorectal cancer through regulating miR-506-3p/KAT6B axis.

Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Circular RNAs may play important roles in the progression of CRC. In this study, we investigated the roles and mechanisms of action of circ-MALAT1 in CRC. Gene expression and protein abundance were determined using qRT-PCR and western blot, respectively. Cell proliferation and migration were assessed by MTT, clone formation, and wound-healing assays. The interactions among the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (circ-MALAT1), miR-506-3p, and lysine acetyltransferase 6B (KAT6B) were predicted using the StarBase software and confirmed by the luciferase activity assay. Circ-MALAT1 and KAT6B were upregulated, while miR-506-3p was downregulated in CRC cells. We validated that knocking down of circ-MALAT1 suppressed proliferation, migration, and epithelial-mesenchymal transition (EMT) of CRC cells, and these effects were abolished by miR-506-3p downregulation or KAT6B sufficiency. Our study suggests that circ-MALAT1 could sponge miR-506-3p to regulate the expression of KAT6B. Moreover, KAT6B sufficiency could neutralize miR-506-3p-dependent growth arrest, migration, and EMT. Circ-MALAT1 promotes cell proliferation, migration, and EMT of CRC cells via the miR-506-3p/KAT6B axis, thereby acting as a novel potential therapeutic target for the treatment of colorectal cancer.

CircPTK2 accelerates tumorigenesis of colorectal cancer by upregulating AKT2 expression via miR-506-3p.

With the rapid increase in its incidence in the last decade, colorectal cancer (CRC) is becoming one of the most life-threatening cancers. Circular RNA PTK2 (circPTK2) has multiple functions in oncogenesis, including in CRC. However, it remains elusive if circPTK2 also plays an important role in CRC malignancy. The levels of circPTK2, miR-506-3p, and AKT serine/threonine kinase 2 (AKT2) were measured by qPCR. The protein level of AKT2 was evaluated by western blotting assay. The proliferation, migration, and invasion of CRC cancer cells were evaluated by MTT, colony formation, wound-healing, and transwell assays. The interaction between circPTK2 and miR-506-3p and between miR-506-3p and AKT2 mRNA were verified by dual-luciferase reporter assay. The expressions of circPTK2 and AKT2 were elevated in CRC cells, with a concomitant reduction of miR-506-3p. The knockdown of circPTK2 suppressed the proliferation, migration, and invasion of CRC cells. CircPTK2 targeted miR-506-3p and negatively regulated its expression. Furthermore, miR-506-3p overexpression suppressed the CRC progression by downregulating the AKT2 expression. AKT2 overexpression or miR-506-3p inhibition restored the suppression of growth and invasiveness of CRC cancer cells caused by circPTK2 silencing. The circPTK2/miR-506-3p/AKT2 axis plays a novel and essential role in promoting CRC progression, providing potential targets for CRC therapeutic modality.

A glimpse into social perception in light of vitality forms.

The American psychoanalyst and developmental psychologist Daniel Stern's idea of vitality forms might suggest a new solution to explain how other minds are intensely expressed in their actions. Vitality forms characterize the expressive style of actions. The effective perception of vitality forms allows people to recognize the affective states and intentions of others in their actions, and could even open the possibility of properties of objects that are indicated by the given actions. Currently, neurophysiological studies present that there might be a neural mirror mechanism in the dorso-central insula (DCI), middle cingulate cortex (MCC), and other related cerebral areas, which serve to preferably perceive and deliver vitality forms of actions. In this article, possible types of vitality forms related to other minds, which have been brought to particular attention in recent years, have been collected and discussed in the following four areas: (1) Vitality forms on understanding non-verbal intention, (2) on understanding verbal intention, (3) vitality forms as grounding social cognition, and (4) as grounding social emotion. These four areas, however, might refer to an entirety of a binary actor-observer communicative landscape. In this review, we try to simplify the analysis by relying on two fundamental dimensions of criteria: first, the idea of vitality forms is conceived as the most basic way of observing subsequent higher-order dimensions of action, that is, understanding intention in the style of action. Thus, in the first two subsections, the relationships between vitality forms and their roles in understanding non-verbal and verbal intention have been discussed. Second, vitality forms could also be conceived as background conditions of all the other mental categories, that is, vitality forms can ground cognition and emotion in a social context. In the second dimension, the existence of social cognition or emotion depends on the existence of the stylistic kinematics of action. A grounding relation is used to distinguish a ground, that is, vitality forms, and its grounded mental categories. As relating with the domain of social perception, in this review, it has been discussed vitality forms possibly could ground social cognition and social emotion, respectively.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex may reduce impulsivity in patients with methamphetamine use disorders: A pilot study.

Background: Individuals who use methamphetamine (MA) for a long period of time may experience decreased inhibition and increased impulsivity. In order to reduce impulsivity or improve inhibitory control ability, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has attracted much attention of researchers. Recent studies on addiction have shown that rTMS can stimulate different brain regions to produce different therapeutic effects. Recent work also suggests that HF-rTMS over right dorsolateral prefrontal cortex (DLPFC) does not affect the impulsivity of patients with alcohol use disorder; while HF-rTMS over left DLPFC could improve the impulsivity of patients with alcohol use disorder and cigarette smokers. However, it should be noted that empirical studies applying HF-rTMS over left DLPFC of patients with MA use disorders (MAUD) (to evaluate its effect on impulsivity) are still lacking. Methods: Twenty-nine patients with MAUD underwent five sessions of HF-rTMS on the left DLPFC per week for 4 consecutive weeks. The cue-induced craving and stop-signal and NoGo task were assessed pre-rTMS and post-rTMS (at the end of the 4-week rTMS treatment). In addition, 29 healthy controls were recruited. There was no rTMS intervention for the controls, the performance of the stop-signal and NoGo task was evaluated on them. Results: In total, HF-rTMS of the left DLPFC significantly decreased MA-dependent patients' cue-induced craving and stop-signal reaction time (SSRT). For SSRT, the pre-test of experimental group was significantly higher than the score of control group. In the experimental group, the pre-test score was significantly higher than the post-test score. For Go and stop-signal delay (SSD), the pre-test scores of the experimental group was significantly lower than the scores of the control group. No significant difference was found between the pre-test and the post-test scores of the experimental group. Conclusion: Add-on HF-rTMS of left DLPFC may be an effective intervention for reducing impulsivity and cue-induced craving of patients with MAUD. Future research with a control group of MAUD that does not undergo the treatment is needed to confirm the effectiveness.

Intermittent Theta Burst Stimulation vs. High-Frequency Repetitive Transcranial Magnetic Stimulation in the Treatment of Methamphetamine Patients.

Background and Aims: In this brief report, we compare the effectiveness and safety of intermittent theta burst stimulation (iTBS) and conventional 10 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with methamphetamine use disorder (MAUD). Our study suggests that iTBS would also reduce drug craving in patients with MAUD just as the 10 Hz; thus, there may be no difference in treatment effects between these two methods. Methods: In total twenty male methamphetamine (MA) addicts were randomly assigned to iTBS (n = 10) or 10 Hz (n = 10) groups for 12 treatments. Cue-evoked cravings, anxiety, depression, and withdrawal symptoms were measured at baseline before the first treatment, and post-tests after days 10, 15, and 20. Results: The results showed that iTBS and 10 Hz treatment had similar effectiveness in reducing cue-induced craving in male addicts for MA. Both 10 Hz and iTBS improved withdrawal symptoms of patients with MAUD. Conclusions: Intermittent theta burst stimulation may be similar in effectiveness as 10 Hz in treating patients with MAUD. The clinical usefulness of rTMS could be improved substantially because of the increase in its capacity, cost, and accessibility. Importantly, the effectiveness of rTMS in the treatment of patients with MAUD is not yet proven, and should be tested in the large double-blind sham-controlled studies.

Effects of Smart City Construction on the Quality of Public Occupational Health: Empirical Evidence From Guangdong Province, China.

This article takes the Guangdong Province of China as the research object and uses the difference-in-difference model to evaluate the impact of smart city construction on the quality of public occupational health and intercity differences. The obtained results show that smart city construction significantly improves the quality of public occupational health, and it is still valid after a series of robustness tests. The effect of this policy is stronger in cities that belong to the Pearl River Delta region or sub-provincial level cities. This study indicates that the central government should improve the pilot evaluation system and the performance appraisal mechanism of smart cities from the perspective of top-level design during the process of promoting smart city construction, which aims to correctly guide local governments to promote the construction of smart cities. To achieve the full improvement effect of smart city construction on the quality of public occupational health, local governments should implement smart city strategies in a purposeful and planned way according to the actual situation of the development of the jurisdiction.

ß-HB inhibits the apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis.

OBJECTIVE: Nerve damage can cause severe limb dysfunction and even leave a lifelong disability. The apoptosis of astrocytes may contribute to the nerve damage. In this research, we sought to investigate the effect of ß-HB on nerve damage in vitro. DESIGN: Astrocytes were treated with high glucose (HG) to mimic in vitro model of nerve damage. RT-qPCR and western blot were used to detect expressions of CREB, BDNF, Ki-67, PCNA, Bax, Bcl-2 and cleaved caspase 3 in astrocytes, respectively. MTT was used to measure the cell viability. In addition, flow cytometry was used to detect the cell apoptosis. RESULTS: ß-HB significantly promoted the proliferation and inhibited apoptosis in HG-treated astrocytes. Results showed that of PCNA and Bcl-2 were upregulated, and Bax and cleaved caspase 3 were downregulated after ß-HB stimulated in HG-treated astrocytes. In addition, HG-induced inhibition on BDNF expression in astrocytes was notably reversed by ß-HB. Furthermore, ß-HB promoted the growth and inhibited apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis. CONCLUSION: ß-HB promotes the growth and inhibits the apoptosis of high glucose-treated astrocytes via activation of CREB/BDNF axis, which may serve as a new target for treatment of nerve damage.

Mitigation of methane emission in a rice paddy field amended with biochar-based slow-release fertilizer.

Despite improving soil quality and reducing nitrogen (N) loss in paddy soil, replacing chemical fertilizer with organic fertilizer would significantly accelerate greenhouse gas emission in terms of methane (CH4). The application of slow-release fertilizer has been proposed an effective approach to control CH4 emissions, in addition to reducing N loss. Yet, the understanding of CH4 emissions from paddy fields with the additions of different fertilizers is still less known. Therefore, the effects of different fertilizer treatments, including chemical fertilizer treatment (CF), mixed chemical and organic fertilizer treatment (OF), biochar-based slow-release fertilizer treatment (SF), and no fertilizer control treatment (CK) on CH4 emissions and methanogenic community structure in paddy soils were investigated through a field experiment. Results showed that slow-release fertilizer addition significantly decreased CH4 emissions by 33.4%, during the whole rice growing season compared to those in OF. The cumulative CH4 emissions were in a significantly positive relation to soil NH4+-N. Slow-release fertilizer amendment decreased the relative abundances of Methanosarcina and Methanoregula and increased the relative abundances of hydrogenotrophic Methanocella and Rice Cluster I. Reduced CH4 emissions with slow-release fertilizer amendment might be mainly attributed to the different forms of N in the fertilizer and available potassium (K) in the paddy soil. Our findings produce novel insights into the application of slow-release fertilizer in controlling CH4 emissions from rice fields.

Anti-Sway and Positioning Adaptive Control of a Double-Pendulum Effect Crane System With Neural Network Compensation.

Cranes are widely used in the field of construction, logistics, and the manufacturing industry. Cranes that use wire ropes as the main lifting mechanism are deeply troubled by the swaying of heavy objects, which seriously restricts the working efficiency of the crane and even cause accidents. Compared with the single-pendulum crane, the double-pendulum effect crane model has stronger nonlinearity, and its controller design is challenging. In this paper, cranes with a double-pendulum effect are considered, and their nonlinear dynamical models are established. Then, a controller based on the radial basis function (RBF) neural network compensation adaptive method is designed, and a stability analysis is also presented. Finally, the hardware-in-the-loop experimental results show that the neural network compensation control can effectively improve the control performance of the controller in practice.

CircATRNL1 protects against osteoarthritis by targeting miR-153-3p and KLF5.

BACKGROUND: Osteoarthritis (OA) is characterized by chondrocyte injury. Circular RNAs (circRNAs) are involved in the pathogenesis of various diseases, including OA. The purpose of this study was to determine the potential role of circATRNL1 in OA pathology in vitro. METHODS: Human chondrocytes were isolated and treated with interleukin-1 beta (IL-1ß) to mimic OA in vitro. High-throughput RNA sequencing was performed to identify differentially expressed circRNAs, miRNAs and mRNAs between IL and 1ß-treated chondrocytes and normal chondrocytes. The expression of circATRNL1, miR-153-3p and KLF5 was measured using quantitative real-time polymerase chain reaction (qRT-PCR). For functional analyses, cell apoptosis was assessed using a flow cytometry assay. Extracellular matrix (ECM) degradation was monitored by measuring the levels of ECM-associated proteins by Western blot. The potential target miRNAs of circATRNL1 were screened by bioinformatics analysis and verified by dual-luciferase reporter assay. RESULTS: The expression of circATRNL1 was decreased in IL-1ß-treated chondrocytes. CircATRNL1 overexpression ameliorated cell apoptosis and ECM degradation, which were promoted by IL-1ß treatment. Mechanistic analysis revealed that circATRNL1 directly targeted miR-153-3p and that miR-153-3p could reverse the inhibitory effects of circATRNL1 overexpression on inflammatory responses, cell apoptosis and ECM degradation. KLF5 is a target of miR-153-3p. CONCLUSION: Taken together, the results in this study suggested that circATRNL1 might ameliorate the development and progression of OA through regulating miR-153-3p/KLF5 axis. Our study increased the understanding of circRNAs as therapeutic targets in the treatment of OA.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

3D culture technologies of cancer stem cells: promising ex vivo tumor models.

Cancer stem cells have been shown to be important in tumorigenesis processes, such as tumor growth, metastasis, and recurrence. As such, many three-dimensional models have been developed to establish an ex vivo microenvironment that cancer stem cells experience under in vivo conditions. Cancer stem cells propagating in three-dimensional culture systems show physiologically related signaling pathway profiles, gene expression, cell-matrix and cell-cell interactions, and drug resistance that reflect at least some of the tumor properties seen in vivo. Herein, we discussed the presently available Cancer stem cell three-dimensional culture models that use biomaterials and engineering tools and the biological implications of these models compared to the conventional ones.

ORF Capture-Seq as a versatile method for targeted identification of full-length isoforms.

Most human protein-coding genes are expressed as multiple isoforms, which greatly expands the functional repertoire of the encoded proteome. While at least one reliable open reading frame (ORF) model has been assigned for every coding gene, the majority of alternative isoforms remains uncharacterized due to (i) vast differences of overall levels between different isoforms expressed from common genes, and (ii) the difficulty of obtaining full-length transcript sequences. Here, we present ORF Capture-Seq (OCS), a flexible method that addresses both challenges for targeted full-length isoform sequencing applications using collections of cloned ORFs as probes. As a proof-of-concept, we show that an OCS pipeline focused on genes coding for transcription factors increases isoform detection by an order of magnitude when compared to unenriched samples. In short, OCS enables rapid discovery of isoforms from custom-selected genes and will accelerate mapping of the human transcriptome.

Model to Predict Overall Survival in Patients With Hepatocellular Carcinoma After Curative Hepatectomy.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) remains difficult to accurately predict. The purpose of this study was to establish a prognostic model for HCC based on a novel scoring system. METHODS: Five hundred and sixty patients who underwent a curative hepatectomy for treatment of HCC at our hospital between January 2007 and January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. The nomogram construction was based on Cox proportional hazard regression models, and the development of the new scoring model was analyzed using receiver operating characteristic (ROC) curve analysis and then compared with other clinical indexes. The novel scoring system was then validated with an external dataset from a different medical institution. RESULTS: Multivariate analysis showed that tumor size, portal vein tumor thrombus (PVTT), invasion of adjacent tissues, microvascular invasion, and levels of fibrinogen and total bilirubin were independent prognostic factors. The new scoring model had higher area under the curve (AUC) values compared to other systems, and the C-index of the nomogram was highly consistent for evaluating the survival of HCC patients in the validation and training datasets, as well as the external validation dataset. CONCLUSIONS: Based on serum markers and other clinical indicators, a precise model to predict the prognosis of patients with HCC was developed. This novel scoring system can be an effective tool for both surgeons and patients.