Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells.

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.

Effects of chlorophyll fluorescence on environment and gross primary productivity of moso bamboo during the leaf-expansion stage.

Chlorophyll fluorescence is the long-wave light released by the residual energy absorbed by vegetation after photosynthesis and dissipation, which can directly and non-destructively reflect the photosynthetic state of plants from the perspective of the mechanism of photosynthetic process. Moso bamboo has a substantial carbon sequestration ability, and leaf-expansion stage is an important phenological period for carbon sequestration. Gross primary production (GPP) is a key parameter reflecting vegetation carbon sequestration process. However, the ability of chlorophyll fluorescence in moso bamboo to explain GPP changes is unclear. The research area of this study is located in the bamboo forest near the flux station of Anji County, Zhejiang Province, where an observation tower is built to monitor the carbon flux and meteorological change of bamboo forest. The chlorophyll fluorescence physiological parameters (Fp) and fluorescence yield (Fy) indices were measured and calculated for the leaves of newborn moso bamboo (I Du bamboo) and the old leaves of 4- to 5-year-old moso bamboo (Ⅲ Du bamboo) during the leaf-expansion stage. The chlorophyll fluorescence in response to the environment and its effect on carbon flux were analyzed. The results showed that: Fv/Fm, Y(II) and α of Ⅰ Du bamboo gradually increased, while Ⅲ Du bamboo gradually decreased, and FYint and FY687/FY738 of Ⅰ Du bamboo were higher than those of Ⅲ Du bamboo; moso bamboo was sensitive to changes in air temperature(Ta), relative humidity(RH), water vapor pressure(E), soil temperature(ST) and soil water content (SWC), the Fy indices of the upper, middle and lower layers were significantly correlated with Ta, E and ST; single or multiple vegetation indices were able to estimate the fluorescence yield indices well (all with R2 greater than 0.77); chlorophyll fluorescence (Fp and Fy indices) of Ⅰ Du bamboo and Ⅲ Du bamboo could explain 74.4% and 72.7% of the GPP variation, respectively; chlorophyll fluorescence and normalized differential vegetation index of the canopy (NDVIc) could estimate GPP well using random forest (Ⅰ Du bamboo: r = 0.929, RMSE = 0.069 g C·m-2; Ⅲ Du bamboo: r = 0.899, RMSE = 0.134 g C·m-2). The results of this study show that chlorophyll fluorescence can provide a basis for judging the response of moso bamboo to environmental changes and can well explain GPP. This study has important scientific significance for evaluating the potential mechanisms of growth, stress feedback and photosynthetic carbon sequestration of bamboo.

Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells.

PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin-1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin-1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si-PAK4, LIMK1, and si-PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK-8, wound-healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co-immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin-1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice. RESULTS: The expression of PAK4/LIMK1/Cofilin-1 in both osteosarcoma tissues and cells was up-regulated. Positive PAK4, LIMK1, and Cofilin-1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p-LIMK/LIMK, and p-Cofilin-1/Cofilin-1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co-immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells. CONCLUSION: The expression of PAK4/LIMK1/Cofilin-1 pathway in osteosarcoma tissues was up-regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin-1 pathway.

Direction Selectivity of TmY Neurites in Drosophila.

The perception of motion is an important function of vision. Neural wiring diagrams for extracting directional information have been obtained by connectome reconstruction. Direction selectivity in Drosophila is thought to originate in T4/T5 neurons through integrating inputs with different temporal filtering properties. Through genetic screening based on synaptic distribution, we isolated a new type of TmY neuron, termed TmY-ds, that form reciprocal synaptic connections with T4/T5 neurons. Its neurites responded to grating motion along the four cardinal directions and showed a variety of direction selectivity. Intriguingly, its direction selectivity originated from temporal filtering neurons rather than T4/T5. Genetic silencing and activation experiments showed that TmY-ds neurons are functionally upstream of T4/T5. Our results suggest that direction selectivity is generated in a tripartite circuit formed among these three neurons-temporal filtering, TmY-ds, and T4/T5 neurons, in which TmY-ds plays a role in the enhancement of direction selectivity in T4/T5 neurons.

Effects of Wheat Tempering with Slightly Acidic Electrolyzed Water on the Microbiota and Flour Characteristics.

Slightly acidic electrolyzed water (SAEW) was prepared and used as wheat tempering water. This study explored the impacts of tempering with SAEW on microbial load and diversity and quality properties of wheat flour. As SAEW volume ratio increased, the residual level of total plate counts (TPC) and mould/yeast counts (MYC) decreased dramatically (p < 0.05). Based on genomics analysis, bacterial 16S rRNA gene and fungal ITS1 gene region were performed to characterize the changes in microbial communities' composition and diversity in response to SAEW treatment. SAEW optimal volume ratio (6.5:10, v/v) of SAEW with distilled water influenced wheat microbiome composition, with a higher microbial diversity and abundance discovered on the control grains. Bacteroidetes of predominant bacterial phylum and Ascomycota of the most abundant fungal phylum were reduced after SAEW optimal volume ratio tempering. The flour yield is higher and ash content is lower than the control samples. Falling number and "b*" in terms of colour markedly increased. DSC (Differential Scanning Calorimetry) test showed that To (onset temperature), Tp (peak temperature), and Tc (conclusion temperature) were significantly decreased in thermal characteristics of flour. Gluten content, protein content, ΔH and pasting properties tests showed no significant change. It can be concluded that SAEW should be applied on wheat tempering for producing clean wheat flour. ANOVA and Tukey's honestly significant difference (HSD) test were used for the analysis of variance and differences between the experimental and control groups, with p < 0.05.

Sunday Driver Mediates Multi-Compartment Golgi Outposts Defects Induced by Amyloid Precursor Protein.

Golgi defects including Golgi fragmentation are pathological features of Alzheimer's disease (AD). As a pathogenic factor in AD, amyloid precursor protein (APP) induces Golgi fragmentation in the soma. However, how APP regulates Golgi outposts (GOs) in dendrites remains unclear. Given that APP resides in and affects the movements of GOs, and in particular, reverses the distribution of multi-compartment GOs (mcGOs), we investigated the regulatory mechanism of mcGO movements in the Drosophila larvae. Knockdown experiments showed that the bidirectional mcGO movements were cooperatively controlled by the dynein heavy chain (Dhc) and kinesin heavy chain subunits. Notably, only Dhc mediated APP's regulation of mcGO movements. Furthermore, by loss-of-function screening, the adaptor protein Sunday driver (Syd) was identified to mediate the APP-induced alteration of the direction of mcGO movements and dendritic defects. Collectively, by elucidating a model of bidirectional mcGO movements, we revealed the mechanism by which APP regulates the direction of mcGO movements. Our study therefore provides new insights into AD pathogenesis.

Influence of angle kappa and angle alpha on visual quality after implantation of multifocal intraocular lenses.

PURPOSE: To assess the influence of angle kappa (κ) and angle alpha (α) on visual quality after multifocal intraocular lens (IOL) implantation. SETTING: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. DESIGN: Prospective case series. METHODS: Patients with cataract had phacoemulsification with TECNIS Symfony IOL implantation. The preoperative angle κ and angle α were measured using the iTrace device. Distance, intermediate, and near visual acuities were recorded 3 months postoperatively. The Optical Quality Analyzing System was used to measure the objective scatter index (OSI), modulation transfer function (MTF) cutoff frequency, and Strehl ratio. A patient questionnaire was also administered. RESULTS: The study comprised 29 patients (57 eyes). Monocularly, the mean postoperative logarithm of the minimum angle of resolution (logMAR) uncorrected distance, intermediate, and near visual acuities were 0.03 ± 0.09 (SD), 0.05 ± 0.11, and 0.11 ± 0.09, respectively. The mean postoperative logMAR corrected distance, distance-corrected intermediate, and distance-corrected near visual acuities were -0.01 ± 0.05, 0.04 ± 0.09, and 0.11 ± 0.08, respectively. The mean OSI, MTF cutoff, and Strehl ratio were 1.27 ± 0.84, 32.03 ± 10.80 cycles per degree, and 0.17 ± 0.05, respectively. The OSI (r = 0.398, P = .005), MTF (r = -0.437, P = .002), and Strehl ratio (r = -0.419, P = .003) values were significantly correlated with angle κ. There was no correlation with angle α. CONCLUSIONS: Angle κ affected the objective visual quality multifocal after IOL implantation. The decision to implant a multifocal IOL should be carefully considered for patients with a large angle κ.

GM130 is required for compartmental organization of dendritic golgi outposts.

Golgi complexes (Golgi) play important roles in the development and function of neurons [1-3]. Not only are Golgi present in the neuronal soma (somal Golgi), they also exist in the dendrites as Golgi outposts [4-7]. Previous studies have shown that Golgi outposts serve as local microtubule-organizing centers [8] and secretory stations in dendrites [6, 9]. It is unknown whether the structure and function of Golgi outposts differ from those of somal Golgi. Here we show in Drosophila that, unlike somal Golgi, the biochemically distinct cis, medial, and trans compartments of Golgi are often disconnected in dendrites in vivo. The Golgi structural protein GM130 is responsible for connecting distinct Golgi compartments in soma and dendritic branch points, and the specific distribution of GM130 determines the compartmental organization of dendritic Golgi in dendritic shafts. We further show that compartmental organization regulates the role of Golgi in acentrosomal microtubule growth in dendrites and in dendritic branching. Our study provides insights into the structure and function of dendritic Golgi outposts as well as the regulation of compartmental organization of Golgi in general.