Knocking down SOX2 overcomes the resistance of prostate cancer to castration via notch signaling.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a terminal type of advanced cancer resistant to androgen deprivation therapy (ADT). Due to the poor therapeutic response of CRPC, novel treatment strategies are urgently required. This study aimed to clarify the regulatory roles of the SOX2/Notch axis in CRPC. METHODS: For the evaluation of the SOX2, Notch, and Hey1 expression in the prostate cancer (PCa) and CRPC tissues, we conducted immunohistochemistry (IHC) analyses. RT-PCR, Western blotting, and immunofluorescence were performed to evaluate SOX2 and Notch expression in enzalutamide-resistant LNCaP cells (Enza-R). CCK-8, Transwell, Wound healing, and Western blotting assays were used to assess the viability, invasion, migration, cell cycle, and drug-resistant in Enza-R cells. RESULTS: Compared to the PCa tissues, CRPC tissues exhibited significantly elevated SOX2, Notch1, and Hey1 expression. SOX2-positive patients were more likely to develop bone metastases than SOX2-negative ones. Significant activation of the signaling associated with SOX2 and Notch was detected in Enza-R cells. The suppression of SOX2 clearly inactivated the Notch signaling and inhibited malignant behaviors, including proliferation, invasion, migration, and drug resistance in Enza-R cells. Theγsecretase inhibitor, GSI-IX, abrogated the enzalutamide resistance by inhibiting Notch signaling in vitro in vitro. Also, GSI-IX alone had a significant anti-tumor effect in Enza-R cells. CONCLUSION: We demonstrated that SOX2/Notch signaling was responsible for Enzalutamide resistance in CRPC. Targeting SOX2/Notch signaling might represent a new choice for the treatment and therapy of CRPC.

Development and Validation of a Tunable Diode Laser Absorption Spectroscopy System for Hot Gas Flow and Small-Scale Flame Measurement.

TDLAS (tunable diode laser absorption spectroscopy) is an important gas analysis method that can be employed to obtain characteristic parameters non-invasively by the infrared absorption spectra of tracer molecules such as CH4, H2O and O2. In this study, a portable H2O-based TDLAS system with a dual optical path was developed with the aim of assessing the combustion characteristics of flammable gases. Firstly, a calculation method of gas characteristics including temperature and velocity combining absorption spectra and a HITRAN database was provided. Secondly, to calibrate and validate this TDLAS system precisely, a pressure vessel and a shock tube were introduced innovatively to generate static or steady flow fields with preset constant temperatures, pressures, or velocities. Static tests within environment pressures up to 2 MPa and steady flow field tests with temperatures up to 1600 K and flow velocities up to 950 m/s were performed for verification. It was proved that this system can provide an accurate values for high temperature and velocity gas flows. Finally, an experimental investigation of CH4/air flames was conducted to test the effectiveness of the system when applied to small diffusion flames. This TDLAS system gave satisfactory flame temperature and velocity data owing to the dual optical path design and high frequency scanning, which compensated for scale effects and pulsation of the flame. This work demonstrates a valuable new approach to thermal hazard analysis in specific environments.

Identification of co-expressed genes and immune infiltration features related to the progression of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease that affects arterial walls and is a leading cause of cardiovascular disease. Gene co-expression modules can provide insight into the molecular mechanisms underlying atherosclerosis progression. In this study, gene co-expression network analysis (WGCNA) was done to identify gene co-expression modules associated with atherosclerosis progression. Before conducting WGCNA, preprocessing and soft power selection were performed on the GSE28829, GSE100927, GSE43292, GSE10334, and GSE16134 datasets ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi ). Co-expression modules were identified using dynamic tree cuts, and their correlations and trait associations were visualized. Enrichment analysis was performed on the blue and magenta modules to identify biological processes (BP) and pathways related to atherosclerosis. The CIBERSORT algorithm was used to predict immune cell infiltration in early and advanced atherosclerotic plaques. We identified 12 co-expression modules, in which blue and magenta were most highly correlated with atherosclerosis progression. The blue module was enriched for inflammation- and immune-related BP and pathways, including phagosome, lysosome, osteoclast differentiation, chemokine signaling pathway, platelet activation, NF-kappa B signaling pathway, Fc gamma R-mediated phagocytosis, lipid and atherosclerosis, autophagy, and apoptosis. The magenta module was significantly enriched for vascular permeability regulation, positive and negative regulation of epithelial to mesenchymal transition, and lamellipodium. Additionally, the CIBERSORT algorithm predicted less abundance of T regulatory cells and monocytes in advanced compared to early atherosclerotic plaques. The enrichment analysis of BP, cellular components, molecular functions, and atherosclerosis-related pathways in the blue and magenta modules showed that inflammation and immune response played a key role in the progression of atherosclerosis. Our study provides insights into the molecular mechanisms underlying atherosclerosis progression and identifies potential therapeutic targets for the treatment of atherosclerosis. The identification of immune cell subtypes associated with atherosclerosis could lead to the development of immunomodulatory therapies to prevent or treat atherosclerosis.

Reprogramming of a human induced pluripotent stem cell line from a long QT syndrome patient harboring a heterozygous mutation of c.1537C > T in SCN5A gene.

Long QT syndrome (LQTS) often causes malignant arrhythmia and syncope. Mutations in the SCN5A gene are the main cause of type 3 LQTS. In this study, we generated a human induced pluripotent stem cell line ZJYYPHi001-A from a female LQTS patient harboring a heterozygous mutation in SCN5A using non-integrative Sendai virus. This cell line expressed pluripotency markers, had the normal karyotype and could differentiate into three germ layers in vitro.

The association between serine hydroxymethyl transferase 1 gene hypermethylation and ischemic stroke.

This study aimed to determine the correlation between serine hydroxymethyl transferase 1 (SHMT1) gene methylation and ischemic stroke. A total of 202 age- and sex-matched individuals were included. Quantitative methylation-specific polymerase chain reaction (qMSP-PCR) was used to analyze the DNA methylation level. The plasma homocysteine (Hcy) concentration was much higher in ischemic cases than in controls (p = 0.009), while the high-density lipoprotein (HDL) levels in stroke cases were considerably lower than in controls (p = 0.005). A significantly higher level of SHMT1 methylation was observed in the ischemic strokes (58.82 ± 17.83%) compared to that in the controls (42.59 ± 20.76%, p < 0.001). The SHMT1 methylation level was strongly correlated with HDL concentration in the healthy controls (r = 0.517, p < 0.001), while the high plasma level of Hcy showed strong association with SHMT1 methylation in ischemic strokes (r = 0.346, p < 0.001). Receiver operating characteristic (ROC) analysis of curve indicated that SHMT1 methylation has been an acceptable indicator for ischemic stroke in female patients [all sexes, area under the curve (AUC) = 0.71, p < 0.001; male patients AUC = 0.62, p = 0.032; and female patients AUC = 0.79, p < 0.001] and in all ages (AUC = 0.71, p < 0.001). In our samples, DNA methylation levels of the STHMI gene were significantly correlated with ischemic stroke in Han Chinese. STHMI hypermethylation was significantly associated with the high Hcy concentration in ischemic stroke and had value as a potential indicator for female ischemic stroke.

[Clinical observation of different needle retention times for acute lumbar sprain treated with float needle].

OBJECTIVE: To observe the difference of the clinical effects of different needle retention times for acute lumbar sprain treated with float needle. METHODS: One hundred and twenty patients with acute lumbar sprain were randomly divided into a 6 h group, a 12 h group, a 24 h group and a western medication group, 30 cases in each one. In the three float needle groups, plastic hose was detained near the pressure pain point on the lumbar after subcutaneous scattering with float needle. The needle retention time was 6 h, 12 h and 24 h respectively. In the western medication group, 75 mg voltaren tablet was adopted orally every day and the treatment was given for four days. Visual analogue scale (VAS) and Oswestry dysfunction index (ODI) about low back pain were observed before and after treatment. Also, the comprehensive effect was assessed after treatment. RESULTS: After treatment, the VAS scores and the ODI scores were improved obviously than those before treatment in all groups (all P< 0. 05). In the three float needle groups, the VAS scores and the ODI scores were superior to those in the western medication group (all P<0. 05). The differences in VAS scores and ODI scores among the three float needle groups were not statistically significant after treatment (all P>0. 05). The effective rate in the 6 h, 12 h and 24 h group was 93. 3% (28/30), 90. 0% (27/30) and 93. 3% (28/30) respectively, which were better than 73. 3% (22/30) in the western medication group (all P<0. 05). CONCLUSION: The effect of float needle for acute lumbar sprain is better than voltaren, and there is no apparent difference in retention times.

[Influence of the substrate composition in extensive green roof on the effluent quality].

By monitoring the effluent quality from different green roof assemblies during several artificial rain events, the main pollutant characteristics and the influence of substrate composition in extensive green roof on the effluent quality were studied. Results showed that the main pollutants in the effluent were N, P and COD; with the increase of cumulative rain, the concentrations of pollutants in the effluent decreased, which had obvious leaching effect; The average concentrations of heavy metals in the early effluent from all assemblies reached drinking water standard, including the assemblies using crushed bricks; When garden soil and compost were used as organic matter, the assemblies had serious leaching of nutrient substance. After the accumulated rainfall reached 150 mm, the TN, TP and COD concentrations of effluent were 2.93, 0.73 and 78 mg x L(-1), respectively, which exceeded the Surface water V class limit. By means of application of the Water Treatment Residual, the leaching of TP from green planting soil was decreased by about 60%. The inorganic compound soil had better effluent quality, however we also need to judge whether the substrate could be applied in extensive green roof or not, by analyzing its ability of water quantity reduction and the plant growth situation.

[Therapeutic effect of triple puncture at Tianzong (SI 11) as main method on obstinate tennis elbow].

OBJECTIVE: To compare the therapeutic effects of triple puncture at Tianzong (SI 11) and routine acupuncture on obstinate tennis elbow. METHODS: Sixty-two cases were randomly divided into 2 groups. The treatment group of 32 cases were treated with triple puncture at Tianzong (SI 11) combined with local points of the elbow, and the control group of 30 cases were treated with local points of the elbow. After one therapeutic course, changes of the symptoms and signs between the two groups were compared. RESULTS: The cured rate of 71.900 in the treatment group was significantly better than 43.3% in the control group (P < 0.05). CONCLUSION: Triple puncture combined with routine acupoint selection therapy has a better therapeutic effect on obstinate tennis elbow than the routine acopoint selection therapy.