CircRNA_0044556 affects the sensitivity of triple-negative breast cancer cells to paclitaxel by regulating miR-665.

CircRNAs have been implicated in the development of resistance in triple-negative breast cancer (TNBC). However, the association between circRNA_0044556 and paclitaxel (PTX) resistance in TNBC is still limited. Therefore, the purpose of this study was to investigate the effect of circRNA_0044556 on biological function and PTX resistance in TNBC cells. PTX-resistant TNBC cells (MDA-MB-231/PTX) were obtained by continuously exposing MDA-MB-231 cells to increasing paclitaxel levels. The expression levels of circRNA_0044556 and miR-665 were measured by qRT-PCR. The regulatory relationship between miR-665 and circRNA_0044556 was verified by biological information website analysis and double-luciferase reporter gene detection experiments. MTT assay, clone assay, flow cytometry and Western blot analysis were used to evaluate the influence of cell biological function. Elevated circRNA_0044556 was observed in TNBC, and paclitaxel increased the expression of circRNA_0044556 in TNBC cells. In TNBC, circRNA_0044556 acted as a ceRNA for miR-665. In addition, low expression of circRNA_0044556 combined with miR-665 inhibited the proliferation of TNBC cells and paclitaxel-resistant TNBC cells while inducing cell death. Our study demonstrated that the downregulation of circRNA_0044556 inhibits the malignant progression of TNBC cells and paclitaxel resistance via miR-665. Thus, circRNA_0044556 may be a potential therapeutic target for PTX-resistance TNBC.

An explainable multiscale LSTM model with wavelet transform and layer-wise relevance propagation for daily streamflow forecasting.

Developing an accurate and reliable daily streamflow forecasting model is important for facilitating the efficient resource planning and management of hydrological systems. In this study, an explainable multiscale long short-term memory (XM-LSTM) model is proposed for effective daily streamflow forecasting by integrating the à trous wavelet transform (ATWT) for decomposing data, the Boruta algorithm for identifying model inputs, and the layer-wise relevance propagation (LRP) for explaining the prediction results. The proposed XM-LSTM is tested by performing multi-step-ahead forecasting of daily streamflow at four stations in the middle and lower reaches of the Yangtze River basin and compared with the X-LSTM. The X-LSTM is formed by coupling the long short-term memory (LSTM) with the LRP. For comparison, the inputs of these two models are identified by the Boruta selection algorithm. The results show that all models exhibit good ability to forecast daily streamflow, however, the prediction performance decreases as the lead time increases. The XM-LSTM provides a better forecasting performance than the X-LSTM, suggesting the ability of the ATWT to improve the LSTM for daily streamflow forecasting. Moreover, the correlation scores analysis by the LRP shows that the ATWT can extract useful information that influences the daily streamflow from the raw predictors, and the water level has the most significant contribution to streamflow prediction. Accordingly, the XM-LSTM model can be viewed as a potentially useful approach for increasing the accuracy and explainability of streamflow forecasting.

Dissecting the causal relationship between neuroticism and osteoarthritis: a univariable and multivariable Mendelian randomization study.

Background: Mental health has been found to be associated with risk of osteoarthritis (OA), but the causal relationship was not fully clarified. Methods: Two-sample Mendelian randomization (MR) study was conducted to investigate the causal relationship between neuroticism (n = 329,821) and the two most frequently affected parts of osteoarthritis (OA) (knee OA: case/control =24,955/378,169; hip OA: case/control = 15,704/378,169) using large scale summary genome-wide association study (GWAS) data. Inverse variance weighted (IVW), weighted median, and MR-Egger were used to estimate the causal effects. Multiple sensitivity analyses were conducted to examine the robustness of the causal estimates. Multivariable MR analysis was used to estimate the direct effects of neuroticism on OA after accounting for the other OA risk factors. Two-step MR approach was employed to explore the potential mediators of the causal relationship. Results: Univariable MR analysis indicated that 1-SD increase in genetically predicted neuroticism score was associated with an increased risk of knee OA (IVW: OR, 1.17; 95% CI, 1.087-1.26; p = 2.72E-05) but not with hip OA. The causal effects remained significant after accounting for the effects of BMI, alcohol drinking, and vigorous physical activity but were attenuated with adjustment of smoking. Further mediation analysis revealed that smoking initiation mediated a significant proportion of the causal effects of neuroticism on knee OA (proportion of mediation effects in total effects: 22.3%; 95% CI, 5.9%-38.6%; p = 7.60E-03). Conclusions: Neuroticism has significant causal effects on knee OA risk. Smoking might partly mediate the causal relationship. Further studies were warranted to explore the underlying mechanisms and potential use of neuroticism management for OA treatment.

Temperature-mediated diffusion of nanoparticles in semidilute polymer solutions.

The temperature is often a critical factor affecting the diffusion of nanoparticles in complex physiological media, but its specific effects are still to be fully understood. Here, we constructed a temperature-regulated model of semidilute polymer solution and experimentally investigated the temperature-mediated diffusion of nanoparticles using the particle tracking method. By examining the ensemble-averaged mean square displacements (MSDs), we found that the MSD grows gradually as the temperature increases while the transition time from sublinear to linear stage in MSD decreases. Meanwhile, the temperature-dependent measured diffusivity of the nanoparticles shows an exponential growth. We revealed that these temperature-mediated changes are determined by the composite effect of the macroscale property of polymer solution and the microscale dynamics of polymer chain as well as nanoparticles. Furthermore, the measured non-Gaussian displacement probability distributions were found to exhibit non-Gaussian fat tails, and the tailed distribution is enhanced as the temperature increases. The non-Gaussianity was calculated and found to vary in the same trend with the tailed distribution, suggesting the occurrence of hopping events. This temperature-mediated non-Gaussian feature validates the recent theory of thermally induced activated hopping. Our results highlight the temperature-mediated changes in diffusive transport of nanoparticles in polymer solutions and may provide the possible strategy to improve drug delivery in physiological media.

Synthesis of an aggregation-induced emission-based fluorescent probe based on rupestonic acid.

Chinese herbal medicine and Chinese patent medicine have been widely applied for cancer care in China. Rupestonic acid, an active ingredient of Artemisia rupestris L., has recently been confirmed to have certain anti-tumor effects in vitro. In this study, we employed the application of a commonly devoted triphenylamine as a fluorophore and the addition of 2,4-thiazolidinedione as a bridge to integrate rupestonic acid into the AIE system to create an fluorescent probe with anti-tumor properties. The spectral, cytotoxic, and cellular imaging properties of the probe were measured. Its promising responses make possible the application of the probe in antitumor theragnostic systems.

Effect of environmental temperature on semen quality and seminal plasma metabolites of Mediterranean buffalo bulls.

High-quality semen with high viability is critical to improving the in-vitro fertilization efficiency. This study aimed to understand the effect of ambient temperature and humidity on semen quality and seminal plasma biochemical parameters of Mediterranean buffalo in March and July. The metabolites of seminal plasma in two seasons were detected using the UPLC-MS/MS method. The results showed that temperature and humidity index (THI) in March were 66.86 ± 2.98, and 82.94 ± 3.52 in July. Compared with in March, breath frequency, rectal temperature, and heat shock protein 70 expressions of seminal plasma were significantly increased in July (p < 0.05), motility of sperm was dramatically reduced, and sperm deformity rate was significantly increased (p < 0.05). Fructose, acid phosphatase and α-glucosidase in seminal plasma were significantly increased (p < 0.05) in July, while testosterone level was significantly reduced (p < 0.05). Six different metabolites were found in the two groups, which involved in three metabolic pathways, the tricarboxylic acid cycle, glycerophospholipid, glyoxylic acid and dicarboxylic acid. The above results indicate that the increased ambient temperature has obvious side effects on the semen quality of Mediterranean buffalo, and the compromised quality is associated with the change of metabolites related to male hormone secretion, energy metabolism and fatty acid oxidation.

Road Scene Simulation Based on Vehicle Sensors: An Intelligent Framework Using Random Walk Detection and Scene Stage Reconstruction.

Road scene model construction is an important aspect of intelligent transportation system research. This paper proposes an intelligent framework that can automatically construct road scene models from image sequences. The road and foreground regions are detected at superpixel level via a new kind of random walk algorithm. The seeds for different regions are initialized by trapezoids that are propagated from adjacent frames using optical flow information. The superpixel level region detection is implemented by the random walk algorithm, which is then refined by a fast two-cycle level set method. After this, scene stages can be specified according to a graph model of traffic elements. These then form the basis of 3D road scene models. Each technical component of the framework was evaluated and the results confirmed the effectiveness of the proposed approach.

CD93 and GIPC expression and localization during central nervous system inflammation.

CD93 and GAIP-interacting protein, C termius (GIPC) have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during central nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inflammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inflammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopolysaccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunofluorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic translocation and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the first to demonstrate CD93 participation in pathophysiological processes of central nervous system inflammation.

[The activity of special CTLs in diminishing CD55(high) subgroup in human breast cancer MCF-7 cells].

OBJECTIVE: To investigate the activities of cytokine induced killer cells (CIK cells) and specific cytotoxic T lymphocytes (CTL) in killing CD55(high) subgroup in MCF-7 breast cancer cell line. METHODS: The killing effects of CIK cells, and specific CTLs in diminishing CD55(high) subgroup cells were analyzed and compared with those of three chemotherapy drugs. First, the MCF-7 breast cancer cells were treated with different concentrations of three chemotherapeutic drugs, docetaxel, epirubicin and fluorouracil. Then immune cells were isolated from human peripheral blood and were induced to become CIK cells. They were then used to treat CD55(high) and CD55(low) subpopulations in MCF-7 cells. Finally, lymphocytes were isolated from surgical specimens of human axially lymph nodes, and were induced to become tumor-specific CTL in vitro. Their activities in killing CD55(high) and CD55(low) subpopulations in MCF-7 cells were measured as well. RESULTS: The killing rates of docetaxel, epirubicin and fluorouracil on CD55(high) subgroup MCF-7 cells were much lower than on total MCF-7 cells. The killing rate of CIK cells on CD55(high) subgroup cells was(42.72 ± 4.36)%. The killing rates of specific CTLs on CD55(high), CD55(low), and total MCF-7 cells were(52.86 ± 4.45)%, (22.41 ± 2.83)%, and(21.67 ± 4.15)%, respectively. CONCLUSION: Specific CTL possessed more effective killing effects on CD55(high) cells.

[Biological characteristics of CD55(hig); side population in breast cancer cell line MCF-7].

AIM: To determine whether the CD55(hig); expression (CD55(hig);) cells in side population (SP) of the cell line MCF-7 possess characteristics of cancer stem cells. METHODS: Breast cancer cell line MCF-7 was cultured and the nucleic acid dye Hoechst33342 and Verapami were added. Flow cytometry (FCM) was employed to isolate the cells of SP and mian population (MP), the cells were then labeled with CD55 mAb; mean values of fluorescence intensity of CD55 in SP and MP cells were measured. CD55 mAb was used to mark the unsorted MCF-7 cells, the proportion of CD55(hig); cells was determined, and then CD55(hig); cells were sorted and collected, to observe biological characteristics, such as cell morphology, adherence rate, colony formation and cell cycle distribution as well as nude mice implantation. RESULTS: Mean value of fluorescence intensity of CD55 in SP cells was 100.85±4.57, and mean value of fluorescence intensity of CD55 in MP cells was 50.51±4.75; the proportion of CD55(hig); cell in MCF-7 cells was 2.12%; adherent rate of CD55(hig); cells in 24 h was lower than that in CD55(low); cells and 24 h after inoculation adherent rates of both cells had no significant difference (P>0.05); CD55(hig); cells were mostly spherical and kept in a suspended state at 12 hours after inoculation and culture; CD55(hig); cells had the ability of colony formation, the clone-forming rate of CD55(hig); cells was (20.04±1.07)% when the cells were cultured for one week, it was lower than the rate of (27.14±1.07)% in CD55(low); cells (P<0.01); the ratio of G0/G1 resting cells in CD55(hig); cells was (85.4±3.37)% which was higher than that in CD55(low); cells (58.6±2.55)% and in MCF-7 cells (70.73±4.21)%, which had a statistically significant difference (P<0.05). All nude mice implanted with CD55(hig); cells developed the tumor, and the pathological examination of the transplanted tumor had the properties of malignant cells. CONCLUSION: A few CD55(hig); cells were found in breast cancer MCF-7 cells, and most of CD55(hig); cells were quiescent, non-adherent as well as being in a suspended state and being hereditary after cloning, so CD55(hig); cells had biological characteristics of cancer stem cells.

[Screening and identification of a fungal strain functioning in hydroxylation of puerarin].

OBJECTIVE: Puerarin is a Chinese herbal medicine. We isolated a fungus from soil which could convert puerarin to 3'-hydroxypuerarin. METHODS: Strains were cultivated on potato dextrose agar (PDA). The biotransformation product was extracted with an organic solvent and detected on high performance liquid chromatography(HPLC). RESULTS: A total of 186 fungal strains were isolated from soil, and strain NT-01 was determined to transform puerarin into 3'-hydroxypuerarin. The product was identified as 3'-hydroxypuerarin by MS and 1H-NMR and 13C-NMR. The morphology characteristic of strain NT-01 was consistent with Gliocladium deliguescens. Phylogenic analysis on sequences showed that strain NT-01 was clustered together with G. deliguescens and G. viride with high boostrap supporting, so that strain NT-01 was identified as Gliocladium sp. CONCLUSION: Gliocladium strain NT-01 can convert puerarin to 3'-hydroxypuerarin.