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BACKGROUND: Aberrant expression of circular RNA (circRNA) has been demonstrated to be related to atherosclerosis (AS) formation. However, the mechanism of circCHMP5 (also known as hsa_circ_0003575) in AS formation remains unclear. METHODS: Oxidized low-density lipoprotein (ox-LDL) was used to treat human umbilical vein endothelial cells (HUVECs) to construct a cell injury model. The expression level of circCHMP5, miR-532-5p, and Rho-associated protein kinase 2 (ROCK2) was measured using quantitative real-time PCR. Cell cycle, apoptosis, proliferation, and angiogenesis were determined by flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU) assay, and tube formation assay. In addition, the protein expression of apoptosis markers, inflammation factors, and ROCK2 was detected by western blot analysis. The interaction between miR-532-5p and circCHMP5 or ROCK2 was assessed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Our results indicated that circCHMP5 was overexpressed in ox-LDL-induced HUVECs. CircCHMP5 knockdown promoted cell cycle, proliferation, and angiogenesis while inhibiting apoptosis and inflammation in ox-LDL-induced HUVECs. MiR-532-5p could be sponged by circCHMP5, and its inhibitor reversed the negative regulation of si-circCHMP5 on ox-LDL-induced HUVECs injury. ROCK2, a target of miR-532-5p, reversed the inhibition effect of miR-532-5p on ox-LDL-induced HUVECs injury. Furthermore, we confirmed that circCHMP5 upregulated ROCK2 by sponging miR-532-5p. CONCLUSION: To sum up, our data showed that circCHMP5 regulated the miR-532-5p/ROCK2 axis to accelerate ox-LDL-induced HUVECs injury, confirming that circCHMP5 might be a potential target for AS treatment.
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Aterosclerose , MicroRNAs , Humanos , Lipoproteínas LDL/toxicidade , Células Endoteliais da Veia Umbilical Humana , Apoptose , Aterosclerose/genética , Inflamação , MicroRNAs/genética , Proliferação de Células , Quinases Associadas a rhoRESUMO
The rapidly growing power data in smart grids have created difficulties in security management. The processing of large-scale power data with the use of artificial intelligence methods has become a hotspot research topic. Considering the early warning detection problem of smart meters, this paper proposes an abnormal data detection network based on Deep Reinforcement Learning, which includes a main network and a target network composed of deep learning networks. This work uses the greedy policy algorithm to find the action of the maximum value of Q based on the Q-learning method to obtain the optimal calculation policy. It also uses the reward value and discount factor to optimize the target value. In particular, this study uses the fuzzy c-means method to predict the future state information value, which improves the computational accuracy of the Deep Reinforcement Learning model. The experimental results show that compared with the traditional smart meter data anomaly detection method, the proposed model improves the accuracy of meter data anomaly detection.
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Inteligência Artificial , Reforço Psicológico , Algoritmos , RecompensaRESUMO
BACKGROUND: Sanfeng Tongqiao Dripping Pills (SFTQ) has clinically demonstrated a promising therapeutic effect on allergic rhinitis (AR). However, the active ingredients and underlying mechanisms of SFTQ remain unclear. PURPOSE: Exploring the effects, mechanisms, and active ingredients of SFTQ in the treatment of AR is valuable. STUDY DESIGN: The mechanisms of SFTQ and its active ingredients in treating AR were investigated through in vivo and in vitro studies. METHODS: A HDM-induced AR model was established in BALB/c mice. The effects of SFTQ in treating AR were evaluated by AR-like symptoms, EOS count, and pathological changes in the nasal tissue in vivo. The effects of SFTQ active components on epithelial cells (ECs) were evaluated in Poly(I:C) and TNF-α co-stimulated human nasal ECs (RPMI-2650). Additionally, the effects of SFTQ active components on splenocytes proliferation and Th cell differentiation were assessed. A co-culture system of ECs and T lymphocytes was established to investigate the impact of Th2 cells on the structure and function of ECs. The effects of SFTQ ingredients on ECs, T lymphocytes, and the HDM-induced AR model were further confirmed through in vivo and in vivo studies, respectively. RESULTS: SFTQ significantly alleviated AR-like symptoms and pathological changes in the nasal tissue of AR mice. The treatment elevated the expression of Occludin and E-cadherin in the nasal epithelium and reduced the percentage of Th2 cells in cervical lymph nodes (CLN). Among the active compounds of SFTQ, L-Menthone and Pulegone notably downregulated IL-33 levels in activated ECs, while Hesperetin significantly decreased TSLP and IL-33 levels. In the co-culture system of ECs and Th2 cells, exposure to Baicalin, Wogonin, and Pulegone increased the TEER value of ECs, while notably inhibiting the production of TSLP and IL-33. Furthermore, in HDM-induced AR mice, treatments with Baicalin, Luteolin, and Hesperetin effectively inhibited AR-like symptoms. Additionally, Luteolin and Hesperetin significantly reduced the inflammatory cells infiltration and the population of Th2 cells in AR mice. CONCLUSION: SFTQ and its active ingredients effectively alleviated HDM-induced AR in mice by inhibiting Th2 cell differentiation and repairing the nasal epithelial barrier. Our study can provide a scientific basis for SFTQ to be used in clinical treatment of AR.
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Diferenciação Celular , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos BALB C , Mucosa Nasal , Pyroglyphidae , Rinite Alérgica , Células Th2 , Animais , Rinite Alérgica/tratamento farmacológico , Mucosa Nasal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Th2/efeitos dos fármacos , Humanos , Camundongos , Modelos Animais de Doenças , Feminino , Células Epiteliais/efeitos dos fármacos , Ocludina/metabolismo , Citocinas/metabolismo , Linfopoietina do Estroma do TimoRESUMO
Conductive hydrogels have garnered significant interest in the realm of wearable flexible sensors due to their close resemblance to human tissue, wearability, and precise signal acquisition capabilities. However, the concurrent attainment of an epidermal hydrogel sensor incorporating reliable self-healing capabilities, biodegradability, robust adhesiveness, and the ability to precisely capture subtle electrophysiological signals poses a daunting and intricate challenge. Herein, an innovative MXene-based composite hydrogel (PBM hydrogel) with exceptional self-healing, self-adhesive, and versatile functionality is engineered through the integration of conductive MXene nanosheets into a well-structured poly(vinyl alcohol) (PVA) and bacterial cellulose (BC) hydrogel three-dimensional (3D) network, utilizing multiple dynamic cross-linking synergistic repeated freeze-thaw strategy. The hydrogel harnesses the presence of dynamically reversible borax ester bonds and multiple hydrogen bonds between its constituents, endowing it with rapid self-healing efficiency (97.8%) and formidable self-adhesive capability. The assembled PBM hydrogel epidermal sensor possesses a rapid response time (10 ms) and exhibits versatility in detecting diverse external stimuli and human movements such as vocalization, handwriting, joint motion, Morse code signals, and even monitoring infusion status. Additionally, the PBM hydrogel sensor offers the added advantage of swift degradation in phosphate-buffered saline solution (within a span of 56 days) and H2O2 solution (in just 53 min), maintaining an eco-friendly profile devoid of any environmental pollution. This work lays the groundwork for possible uses in electronic skins, interactions between humans and machines, and the monitoring of individualized healthcare.
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Adesivos , Hidrogéis , Nitritos , Elementos de Transição , Humanos , Peróxido de Hidrogênio , Cimentos de Resina , Condutividade ElétricaRESUMO
Conventional bulky and rigid planar architecting power systems are difficult to satisfy the growing demand for wearable applications. 1D fiber batteries bearing appealing features of miniaturization, adaptability, and weavability represent a promising solution, yet challenges remain pertaining to energy density and scalability. Herein, an ingenious densifiable functional ink is invented to fabricate scalable, flexible, and high-mass-loading fiber lithium-ion batteries (LIBs) by adopting a fast ink-extrusion technology. In the formulated ink, pyrrole-modified reduced graphene oxide is elaborately introduced and exerts multiple influences; it not only assembles carbon nanotubes and poly(vinylidene fluoride-co-hexafluoropropylene) to compose a sturdy, conductive, and agglomeration-free 3D network that realizes an ultra-high content (75 wt%) of the active materials and endows the electrode excellent flexibility but also serves as a capillary densification inducer, encouraging an extremely large linear mass loading (1.01 mg cm-1 per fiber) and packing density (782.1 mg cm-3 ). As a result, the assembled fiber LIBs deliver impressive linear and volumetric energy densities with superb mechanical compliance, demonstrating the best performance among all the reported extruded fiber batteries. This work highlights a highly effective and facile approach to fabricate high-performance fiber energy storage devices for future practical wearable applications.
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Background: Phlegm-dampness constitution as one of nine constitutions in traditional Chinese medicine (TCM) has been a high risk factor for glucolipid metabolic disorders (GLMD). Based on our previous findings, Hua Tan Qu Shi recipe (HTQSR) could effectively improve metabolic indicators of GLMD by targeting on phlegm-dampness constitution. However, the proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution remain unknown. Methods: Clinical participants from phlegm-dampness constitution with the prediabetic state (T), phlegm-dampness constitution with marginally elevated blood lipids (Z), and phlegm-dampness constitution before sickness (W) were included in this study, who orally took HTQSR for 12 weeks and, respectively, marked AT, AZ, and AW. Data-independent acquisition (DIA) and parallel reaction monitoring (PRM) were performed to identify the differential proteins; then, Venn analysis was used to investigate coexpressed and coregulated proteins. In addition, ingenuity pathway analysis (IPA) software was utilized to explore the related pathways and diseases and biofunctions. Results: LXR/RXR activation, acute phase response signaling, and production of nitric oxide and reactive oxygen species in macrophages were obviously activated between the T and AT groups, as well as the Z and AZ groups. In contrast, these three pathways were inhibited between the W and AW groups. Importantly, one coexpressed and coregulated differential protein, B2MG, was validated by PRM among all groups. Conclusions: This work firstly reported the underlying proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution, indicating that intervention of phlegm-dampness constitution might be a novel strategy for the preventive treatment of GLMD.
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Doenças Metabólicas , Proteômica , Humanos , Medicina Tradicional Chinesa , Fatores de RiscoRESUMO
OBJECTIVE: The objective of this study is to explore the long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles of monocyte-derived dendritic cells (DCs) obtained from peripheral blood mononuclear cells (PBMCs). DCs are known to play a major role in the regulating function of allergic rhinitis (AR). METHODS: PBMCs were separately isolated from the human peripheral blood of patients with AR and normal person (NP). The mixed lymphocyte reaction (MLR) assay was used to evaluate the function of DCs. Flow cytometry was used to determine the immune regulatory function of immature DCs (imDCs) and mature DCs (mDCs). lncRNAs and mRNAs in the NP group (DCs isolated from NP) and the test group (DCs isolated from patients with AR) were identified via chip technology and bioinformatic analyses. Moreover, bioinformatic analyses were employed to identify the related biological functions of monocyte-derived DCs and construct the functional networks of lncRNAs and mRNAs that are differentially expressed (DE) in imDCs and mDCs. RESULTS: MLR was significantly higher in the mDCs group than that in the imDCs group. CD14 was highly expressed in imDCs, whereas HLA-DR, CD80, and CD86 were highly expressed in mDCs (p < 0.001). We identified 962 DE lncRNAs and 308 DE mRNAs in the imDCs of NP and patients with AR. Additionally, there were 601 DE lncRNAs and 168 DE mRNAs in the mDCs in the NP and test groups. Quantitative RT-qPCR was used to study the significant fold changes of lncRNAs and mRNAs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found 16 significant regulated pathways in imDCs and 10 significant regulated pathways in mDCs, including the phagosome, cell adhesion signaling pathway, and inflammatory mediator regulation of TRP channels pathway. CONCLUSION: Our research studied the lncRNA and mRNA expression profiles of monocyte-derived DCs and demonstrated the functional networks that are involved in monocyte-derived DCs-mediated regulation in AR. These results provided possible molecular mechanisms of monocyte-derived DCs in the immunoregulating function and laid the foundation for the molecular therapeutic targets of AR.
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Transition metal selenides attract extensive attentions in the aspect of electrochemical energy storage due to the good conductivity and significant electrochemical activity. Herein, we develop a facile mothed to synthesize nickel cobalt selenides nanoparticles by hydrothermal approach. Benefiting from the synergistic effect between Co and Ni, the optimized Ni0.6Co0.4Se2 electrode shows a specific capacity of 602.6â¯Câ¯g-1 at 1â¯Aâ¯g-1 and superior rate characteristic (468.5â¯Câ¯g-1 at 20â¯Aâ¯g-1). More interestingly, an all-solid-state asymmetric supercapacitor was constructed utilizing the BNPC material as the negative electrode and the Ni0.6Co0.4Se2 samples as the positive electrode shows a high energy density of 42.1â¯Whâ¯kg-1 and superior cycling stability (91.0% capacity maintenance after 5000 cycles) in KOH/PVA gel electrolyte. These exciting characteristics provide a new idea for the construction of transition metal selenide electrode materials for high performance supercapacitors.
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Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide and the number of individuals at CAD risk is increasing. To better manage cardiovascular disease, improved tools for risk prediction including the identification of novel accurate biomarkers are needed. MicroRNAs (miRNAs) are small non-coding RNAs that modulate the expression of protein-coding genes at the post-transcription level and their dysregulated expression has been implicated in various pathogenic processes including cardiovascular disease. Circulating miRNAs have been widely recommended as potential biomarkers for many diseases including coronary artery disease. In the present study, we found that miR-3646 was significantly upregulated in the serum samples of CAD patients and in the mice with acute myocardial infarction (AMI) compared with the healthy control group via using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Moreover, the serum levels of miR-3646 were significantly positively correlated with the expression of IL-6 both in CAD patient samples and AMI mice samples. In human THP-1 macrophages, transfection with miR-3646 mimic elevated the expression of IL-6 while silence of miR-3646 suppressed the IL-6 level. Further exploration of the downstream targets of miR-3646 identified that blocking RHOH expression also could upregulate IL-6 expression. In addition, our findings also showed that miR-3646 promoted vascular smooth muscle cell (VSMC) proliferation and migration by targeting RHOH. These results demonstrate that the miR-3646-RHOH axis may serve as a key regulator in the progression of CAD by modulating vascular inflammation and regulating the biologic behaviors of VSMCs.
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The effects of Guangxin Dansheng Capsule on activating blood and eliminating stasis, regulating vital energy and alleviating pain were observed. The results showed that Guanxin Dansheng Capsule possessed obvious protective effects on acute cardiac muscle ischemia and could inhibit the aggregation of platelet induced by ADP, reduce the amount of oxygen consumed and prolong time of haemorrhage.