Exploring the microRNA-mRNA regulatory network associated with solasonine in bladder cancer.

Background: Solasonine has been demonstrated to exert an inhibitory effect on bladder cancer (BC), but the potential mechanisms remain unclear. Therefore, the aim of this study is to explore the association between microRNAs (miRNAs)-mediated regulation and the anti-tumor activities of solasonine in BC. Methods: MiRNA sequencing was performed to identify the differentially expressed microRNAs (DE-miRNAs) associated with solasonine in BC cells. Functional enrichment analyses of the DE-miRNAs activated and inhibited by solasonine were then conducted. The DE-miRNAs with prognostic value for BC and those differentially expressed in the BC samples were subsequently identified as the hub DE-miRNAs. After identifying the messenger RNAs (mRNAs) that were targeted by the hub DE-miRNAs and those differentially expressed in the BC samples, a protein-protein interaction analysis was performed to identify the core downstream genes, which were then used to construct a solasonine-miRNA-mRNA regulatory network. Results: A total of 27 activated and 19 inhibited solasonine-mediated DE-miRNAs were identified that were found to be associated with several tumor-related biological functions and pathways. After integrating the results of the survival analysis and expression assessment, the following nine hub DE-miRNAs were identified: hsa-miR-127-3p, hsa-miR-450b-5p, hsa-miR-99a-5p, hsa-miR-197-3p, hsa-miR-423-3p, hsa-miR-4326, hsa-miR-625-3p, hsa-miR-625-5p, and hsa-miR-92a-3p. The DE-mRNAs targeted by the hub DE-miRNAs were predicted, and 30 core downstream genes were used to construct the solasonine-miRNA-mRNA regulatory network. miR-450b-5p was shown to be associated with the most mRNAs in this network, which suggests that it plays a crucial role in the solasonine-mediated anti-BC effect. Conclusions: A regulatory network, including solasonine, miRNAs, and mRNAs related to BC, was constructed. This network provides extensive insights into the molecular regulatory mechanisms that underlie the anti-cancer efficacy of solasonine in BC.

Development and validation of a risk prediction model and prediction tools for post-thrombotic syndrome in patients with lower limb deep vein thrombosis.

PURPOSE: Our research aims to compare the predictive performance of decision tree algorithms (DT) and logistic regression analysis (LR) in constructing models, and develop a Post-Thrombotic Syndrome (PTS) risk stratification tool. METHODS: We retrospectively collected and analyzed relevant case information of 618 patients diagnosed with DVT from January 2012 to December 2021 in three different tertiary hospitals in Jiangxi Province as the modeling group. Additionally, we used the case information of 212 patients diagnosed with DVT from January 2022 to January 2023 in two tertiary hospitals in Hubei Province and Guangdong Province as the validation group. We extracted electronic medical record information including general patient data, medical history, laboratory test indicators, and treatment data for analysis. We established DT and LR models and compared their predictive performance using receiver operating characteristic (ROC) curves and confusion matrices. Internal and external validations were conducted. Additionally, we utilized LR to generate nomogram charts, calibration curves, and decision curves analysis (DCA) to assess its predictive accuracy. RESULTS: Both DT and LR models indicate that Year, Residence, Cancer, Varicose Vein Operation History, DM, and Chronic VTE are risk factors for PTS occurrence. In internal validation, DT outperforms LR (0.962 vs 0.925, z = 3.379, P < 0.001). However, in external validation, there is no significant difference in the area under the ROC curve between the two models (0.963 vs 0.949, z = 0.412, P = 0.680). The validation results of calibration curves and DCA demonstrate that LR exhibits good predictive accuracy and clinical effectiveness. A web-based calculator software of nomogram (https://sunxiaoxuan.shinyapps.io/dynnomapp/) was utilized to visualize the logistic regression model. CONCLUSIONS: The combination of decision tree and logistic regression models, along with the web-based calculator software of nomogram, can assist healthcare professionals in accurately assessing the risk of PTS occurrence in individual patients with lower limb DVT.

New Insights into the Role of Mild Hypoxia in Regulating Neural Stem Cell Characteristics.

The proliferation of neural stem cells (NSCs) is precisely regulated by extracellular environmental factors. In situ hypoxia, one of the key factors involved in the regulation of NSC characteristics, has attracted increasing amounts of attention. Numerous studies have demonstrated that hypoxia can significantly promote the formation of neurospheres and the proliferation of NSCs in vitro and that intermittent hypoxia can promote the proliferation of endogenous NSCs in vivo. In this article, the effects of different concentrations of oxygen on NSC proliferation and differentiation both in vivo and in vitro are reviewed, and the potential applications of hypoxia-preconditioned NSCs, as well as research progress and challenges in the treatment of central nervous system diseases, are further summarized. Here, the critical role of oxygen in the neurogenesis of NSCs is emphasized, and insights into the use of hypoxia to regulate NSC characteristics are provided.

Karyotype and LTR-RTs analysis provide insights into oak genomic evolution.

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.

4 mC site recognition algorithm based on pruned pre-trained DNABert-Pruning model and fused artificial feature encoding.

DNA 4 mC plays a crucial role in the genetic expression process of organisms. However, existing deep learning algorithms have shortcomings in the ability to represent DNA sequence features. In this paper, we propose a 4 mC site identification algorithm, DNABert-4mC, based on a fusion of the pruned pre-training DNABert-Pruning model and artificial feature encoding to identify 4 mC sites. The algorithm prunes and compresses the DNABert model, resulting in the pruned pre-training model DNABert-Pruning. This model reduces the number of parameters and removes redundancy from output features, yielding more precise feature representations while upholding accuracy.Simultaneously, the algorithm constructs an artificial feature encoding module to assist the DNABert-Pruning model in feature representation, effectively supplementing the information that is missing from the pre-trained features. The algorithm also introduces the AFF-4mC fusion strategy, which combines artificial feature encoding with the DNABert-Pruning model, to improve the feature representation capability of DNA sequences in multi-semantic spaces and better extract 4 mC sites and the distribution of nucleotide importance within the sequence. In experiments on six independent test sets, the DNABert-4mC algorithm achieved an average AUC value of 93.81%, outperforming seven other advanced algorithms with improvements of 2.05%, 5.02%, 11.32%, 5.90%, 12.02%, 2.42% and 2.34%, respectively.

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival.

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here, we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.

Insomnia is related to long-term atrial fibrillation recurrence following radiofrequency ablation.

OBJECTIVE: Atrial fibrillation (AF), the most common cardiac arrhythmia, presents significant health challenges, and the intricate connection between insomnia and AF has garnered substantial attention. This cohort study aims to investigate the relationship between insomnia and AF recurrences following radiofrequency ablation. MATERIALS AND METHODS: Data were retrieved from an electronic database of patients who underwent radiofrequency ablation for AF. The primary endpoint was AF recurrence. We utilized a multivariable Cox model, coupled with three propensity score methods, for analysis. RESULTS: Between January 1, 2017, and June 1, 2022, 541 patients who underwent radiofrequency ablation for AF were recorded in the database. After excluding 185 patients, the final cohort comprised 356 patients. Among them, 68 were afflicted by insomnia, while 288 were not. Over a median follow-up of 755 days, one patient died, and 130 (36.5%) experienced AF recurrence. Multivariate Cox regression analysis revealed that the insomnia group had a higher risk of AF recurrence compared to the non-insomnia group (HR: 1.83, 95% CI: 1.16-2.89). Further landmark analysis showed no significant difference in AF recurrence rates during the initial 1-year follow-up. However, beyond 1 year, the insomnia group demonstrated a significantly higher AF recurrence rate. As the number of insomnia symptoms increased, the risk of AF recurrence also rose significantly, indicating a dose-response relationship. CONCLUSION: This study establishes a significant link between insomnia and long-term AF recurrence following radiofrequency ablation. It underscores the importance of identifying and addressing insomnia in patients with AF undergoing radiofrequency ablation.

Optimizing rice grain size by attenuating phosphorylation-triggered functional impairment of a chromatin modifier ternary complex.

Histone acetylation affects numerous cellular processes, such as gene transcription, in both plants and animals. However, the posttranslational modification-participated regulatory networks for crop-yield-related traits are largely unexplored. Here, we characterize a regulatory axis for controlling rice grain size and yield, centered on a potent histone acetyltransferase (chromatin modifier) known as HHC4. HHC4 interacts with and forms a ternary complex with adaptor protein ADA2 and transcription factor bZIP23, wherein bZIP23 recruits HHC4 to specific promoters, and ADA2 and HHC4 additively enhance bZIP23 transactivation on target genes. Meanwhile, HHC4 interacts with and is phosphorylated by GSK3-like kinase TGW3. The resultant phosphorylation triggers several functional impairments of the HHC4 ternary complex. In addition, we identify two major phosphorylation sites of HHC4 by TGW3-sites which play an important role in controlling rice grain size. Overall, our findings thus have critical implications for understanding epigenetic basis of grain size control and manipulating the knowledge for higher crop productivity.

Prediction of miRNA-disease associations based on strengthened hypergraph convolutional autoencoder.

Most existing graph neural network-based methods for predicting miRNA-disease associations rely on initial association matrices to pass messages, but the sparsity of these matrices greatly limits performance. To address this issue and predict potential associations between miRNAs and diseases, we propose a method called strengthened hypergraph convolutional autoencoder (SHGAE). SHGAE leverages multiple layers of strengthened hypergraph neural networks (SHGNN) to obtain robust node embeddings. Within SHGNN, we design a strengthened hypergraph convolutional network module (SHGCN) that enhances original graph associations and reduces matrix sparsity. Additionally, SHGCN expands node receptive fields by utilizing hyperedge features as intermediaries to obtain high-order neighbor embeddings. To improve performance, we also incorporate attention-based fusion of self-embeddings and SHGCN embeddings. SHGAE predicts potential miRNA-disease associations using a multilayer perceptron as the decoder. Across multiple metrics, SHGAE outperforms other state-of-the-art methods in five-fold cross-validation. Furthermore, we evaluate SHGAE on colon and lung neoplasms cases to demonstrate its ability to predict potential associations. Notably, SHGAE also performs well in the analysis of gastric neoplasms without miRNA associations.

Identification of the length and location of the A1 pulley combining palpation technique with palm landmarks: a cadaveric study.

Through anatomical morphology, to accumulate the relevant parameters of the A1 pulley of each adult finger. A total of 100 fingers were selected, dissected layer by layer, and the A1 pulley and neurovascular of each finger were observed. Measure the length of the A1 pulley, the distance between the needle knife insertion point and the proximal edge of A1 pulley, and the nerves and blood vessels on both sides. (1) The length of A1 pulleys of each finger is 6.18 ± 0.33 mm, 6.58 ± 0.73 mm, 5.98 ± 0.67 mm, 5.36 ± 1.08 mm, 5.63 ± 1.09 mm. (2) The distances between the needle knife entry point of each finger and the volar proper nerve of the ulnar finger are 7.00 ± 1.55 mm, 8.29 ± 1.46 mm, 5.10 ± 0.25 mm, 5.30 ± 0.24 mm, 0 mm; the distances from the volar proper nerve of the radial finger are 9.08 ± 0.87 mm, 4.70 ± 1.10 mm, 7.03 ± 0.72 mm, 6.81 ± 0.22 mm, 7.81 ± 0.57 mm. (3) The distances between the needle knife entry point of each finger and the proper volar artery of the ulnar finger are 10.40 ± 0.75 mm, 8.89 ± 0.53 mm, 6.35 ± 0.44 mm, 7.26 ± 0.16 mm, 0 mm, respectively; The distances from the volar proper artery of the radial finger are 8.75 ± 1.07 mm, 6.10 ± 0.35 mm, 11.44 ± 0.41 mm, 8.19 ± 0.60 mm, 9.78 ± 0.68 mm, respectively. The landmarks of the needle entry points are located at the position corresponding to the highest point of the metacarpal heads, except the tail finger. From the needle knife entry point to distal, cut the proximal edge of the A1 pulley longitudinally along the midline until the patient can flex autonomously, and pay attention to the distance between the two sides of 3.60-11.85 mm neurovascular bundle.

Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC). Materials and methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results. Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

[Relationship between acupoint sensitization and changes in dorsal root ganglion neuron excitability in myocardial ischemia mice].

OBJECTIVE: To investigate the relationship between the sensitization state of acupoints on the surface of the myocardial ischemia (MI) model mice and the changes in the electrophysiological properties of the dorsal root ganglion (DRG) neurons in the corresponding spinal cord segment, and its underlying mechanism. METHODS: Sixty-eight male C57BL/6J mice were randomly divided into control and model groups (34 mice in each group). The model group received an intraperitoneal injection of 160 mg/kg isoproterenol (ISO) to establish the MI model, and the control group received an injection of the same dose of normal saline as the model group. After modeling for about 6 days, MI proportion was measured by HE staining to verify the pathological changes in the heart tissue. Evans blue (EB) dye was injected into the tail vein of mice to reflect the size, location, distribution, and number of exudates on the body surface. Then, whole-cell membrane currents, intrinsic excitability and membrane properties of different types of DRG neurons were evaluated by electrophysiological experiment in vitro. RESULTS: Compared with the control group, the heart size was larger, with pathological outcomes showing enlarged myocardial hypertrophy, destroyed structure of cardiomyocytes, with mononuclear cell infiltration among the cardiomyocytes in the model group. Compared with the control group, the number of EB exudation points was significantly increased (P<0.01), which were mainly concentrated in the epidermis near the T1-T5 segment of the spinal cord, "Feishu" (BL13), "Jueyinshu" (BL14) and "Xinshu" (BL15) in the model group. Compared with the control group, the rheobase and action potential amplitude (APA) of DRG medium-sized neurons were obviously decreased (P<0.01, P<0.05), while the whole-cell membrane currents, the spike numbers, the average instantaneous frequency, and the average discharge frequency were markedly increased (P<0.01). There were no significant alterations in the membrane properties and intrinsic excitability induced by depolarized currents of small-sized neurons between groups. Compared with the control group, the whole-cell membrane currents, spike numbers, and the average instantaneous frequency were significantly increased in the model group(P<0.05, P<0.01) while rheobase was significantly decreased (P<0.05) in DRG medium-sized neurons labeled with biotin and CGRP. CONCLUSION: After the mice were modeled by ISO, the DRG medium-size neurons in the T1-T5 segment of the spinal cord may mediate the sensitization of acupoints on the body surface through their different neuronal membrane properties and intrinsic excitabilities.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

A Case of Coma Bullae Associated with Brachioradial Artery.

We present the first case of coma bullae observed in a 67-year-old woman due to pressure and ischemia associated with brachioradial artery. A skin biopsy taken from the ulcer border revealed extensive loss of the epidermis, fibrosis of dermis, mild infiltration by lymphocytes and neutrophils, and necrosis of the focal eccrine ducts. CT angiography of the right upper limb showed a high origin of the radial artery, meanwhile both high originating radial artery and the anastomoses were tortuous and were of relatively small caliber. The diagnosis of coma bullae was made. After tissue debridement, the skin lesions gradually recovered, leaving atrophic scars.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.

[Research progress of Codonopsis Radix and prediction of its Q-markers].

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES.

BACKGROUND: The relationship between dietary total antioxidant capacity (DTAC) and death risk among CKD populations remains unclear. METHODS: Based on vitamin C equivalent antioxidant capacity (VCEAC) and the component dietary antioxidant index (CDAI) indices, we analyzed two cohorts to investigate the association of DTAC with all-cause and CVD mortality in CKD patients using data from National Health and Nutrition Examination Survey (2007-2018). VCEAC (n = 6330) and CDAI (n = 6300) cohorts with mortality follow-up data available through 2018 were included. Cox models with restricted cubic splines was used to model the nonlinear association between VCEAC/CDAI and outcomes in CKD patients. RESULTS: Our results showed L-shaped associations of DTAC with all-cause mortality among individuals with CKD stages 1-2 in both cohorts. Compared to the lowest quartile, higher dietary total antioxidant intake was associated with lower all-cause mortality risks among CKD stages 1-2 after adjustment for covariates, with HRs (95%CI) of 1.00, 0.91 (0.71,1.17), 0.69 (0.53,0.90), and 0.70 (0.54,0.91) in VCEAC, and similar respective estimate trends in CDAI. After sensitivity and subgroup analyses, there were no benefits for patients with stage 3-5 CKD or albuminuria. Mediation analysis revealed that the proportions mediated in both cohorts were less consistent. CONCLUSIONS: Moderate dietary total antioxidants intake has potential benefits for early-stage CKD patients. However, further evidence is needed to confirm whether patients with worsening CKD can benefit in the long term.

A triphenylamine-based fluorescence probe for detection of hypochlorite in mitochondria.

The level of HClO/ClO- in mitochondria is essential to keep the normal function of mitochondria. Therefore, it is meaningful to accurately and quickly monitor ClO- in mitochondria. In this work, a new triphenylamine-based fluorescence probe PDTPA was designed and synthesized, in which pyridinium salt and dicyano-vinyl group were introduced as mitochondria targeting site and reaction site for ClO-. The probe showed high sensitivity and fast fluorescence response (<10 s) in the detection of ClO-. Moreover, the probe PDTPA had good linearity in a wide concentration range of ClO- and its detection limit was calculated as 10.5 µM. Confocal fluorescence images demonstrated that the probe could target mitochondria and track the fluctuations of endogenous/exogenous ClO- levels in the mitochondria of living cells.

[Effect of electroacupuncture on Notch/NF-κB signaling pathway in colonic mucosa of mice with ulcerative colitis].

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) on the intestinal mucosal barrier and its relationship with the Notch/NF-κB signaling pathway in mice with ulcerative colitis (UC), so as to explore its mechanism of treating UC. METHODS: Male C57BL/6J mice were randomized into control, model and EA groups, with 6 mice in each group. The UC model was established by giving the mice with 2% Dextran Sulfate Sodium (DSS) for 7 days. EA (2 Hz/15 Hz, 0.2 mA) was applied at bilateral "Zusanli" (ST36) for 30 min, once a day for 7 days. The disease activity indexes ï¼»DAI=(body weight index score+stool score+bleeding score)/3; 0-4 pointsï¼½ of mice were calculated. The morphological changes of colonic tissues of mice in each group were observed by HE staining, and serum contents of TNF-α and IL-6 were detected by ELISA. Claudin-1 protein expression in colon tissue was detected by immunofluorescence, while the protein expression levels of Muc-2, Notch-1, MMP-9 in colon tissue were detected by immunohistochemistry. The real-time PCR method was used to detect the expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in colon tissues. RESULTS: After modeling, the DAI, serum TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expression levels of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA in the colonic tissue were significantly increased (P<0.001, P<0.01) in the model group relevant to the control group. At the same time, Claudin-1 and Muc-2 protein expression were significantly reduced (P<0.01). After the EA intervention, the increased DAI score, TNF-α and IL-6 contents, Notch-1 and MMP-9 protein expression, the relative expressions of Notch-1, Hes-1, NF-κB, TLR-4 and AKT mRNA, and the decreased Claudin-1 and Muc-2 protein expression were all reversed compared with the model group (P<0.05, P<0.01, P<0.001). H.E. staining of the colonic tissue showed damage and infiltration of inflammatory cells in the model group, and those were significantly improved in the EA group. CONCLUSION: EA can promote the recovery of intestinal mucosal barrier function and reduce inflammatory reaction in UC mice, which may be associated with its effects in inhibiting the excessive activation of the Notch/NF-κB signaling pathway.

GAS6-AS1, a long noncoding RNA, functions as a key candidate gene in atrial fibrillation related stroke determined by ceRNA network analysis and WGCNA.

BACKGROUND: Stroke attributable to atrial fibrillation (AF related stroke, AFST) accounts for 13 ~ 26% of ischemic stroke. It has been found that AFST patients have a higher risk of disability and mortality than those without AF. Additionally, it's still a great challenge to treat AFST patients because its exact mechanism at the molecular level remains unclear. Thus, it's vital to investigate the mechanism of AFST and search for molecular targets of treatment. Long non-coding RNAs (lncRNAs) are related to the pathogenesis of various diseases. However, the role of lncRNAs in AFST remains unclear. In this study, AFST-related lncRNAs are explored using competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA). METHODS: GSE66724 and GSE58294 datasets were downloaded from GEO database. After data preprocessing and probe reannotation, differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) between AFST and AF samples were explored. Then, functional enrichment analysis and protein-protein interaction (PPI) network analysis of the DEMs were performed. At the meantime, ceRNA network analysis and WGCNA were performed to identify hub lncRNAs. The hub lncRNAs identified both by ceRNA network analysis and WGCNA were further validated by Comparative Toxicogenomics Database (CTD). RESULTS: In all, 19 DELs and 317 DEMs were identified between the AFST and AF samples. Functional enrichment analysis suggested that the DEMs associated with AFST were mainly enriched in the activation of the immune response. Two lncRNAs which overlapped between the three lncRNAs identified by the ceRNA network analysis and the 28 lncRNAs identified by the WGCNA were screened as hub lncRNAs for further validation. Finally, lncRNA GAS6-AS1 turned out to be associated with AFST by CTD validation. CONCLUSION: These findings suggested that low expression of GAS6-AS1 might exert an essential role in AFST through downregulating its downstream target mRNAs GOLGA8A and BACH2, and GAS6-AS1 might be a potential target for AFST therapy.