DDT exposure induces tremor-like behavior and neurotoxicity in developmental stages of embryonic zebrafish.

Dichlorodiphenyltrichloroethane (DDT) is a broad-spectrum insecticide, widely detected in environments due to its high stability characteristic and long natural half-life period. The adverse impact of DDT exposure on organisms and humans has attracted great concern worldwide. The current study explored the developmental and neurobehavioral toxicity response of DDT in embryonic zebrafish. The embryos were treated with DDT (0, 0.1, 1, 2.5 and 5 µM) during 6 h post fertilization (hpf) to 144 hpf. Our result indicated that DDT exposures increased the embryo hatching rate at 48 and 60 hpf, the larval malformation rate at 120 hpf and mortality rate at 144 hpf. The manifested malformations included uninflated swim bladder, bent spine and tail, deformed liver, and pericardial edema. The 120 hpf larval organs size of the gut and swim bladder was decreased in higher exposed concentration groups. Besides, DDT exposure resulted in hyperactivity for the embryo spontaneous movement at 24 hpf and tremor like movement measured by the free larval activity at 72 hpf, as well as the larval activity at 96 hpf under light-dark transition stimulus. Mechanistic examinations at 120 hpf revealed DDT exposure elevated oxidative stress through MDA formation increase, ATP level decrease as well as antioxidant enzyme genes (sod1 and gpx1a) expression decrease. DDT exposure induced abnormal neurotransmitters expression with DA level increase, 5-HT and NOS level decrease. DDT exposure suppressed the gene expressions involved in axon development (rab33a and nrxn2a) and potassium channel (kcnq2 and kcnq3). Our results suggest that the hyperactivity and tremor like movement in DDT-exposed embryos/larvae may result from oxidative stress involved with neuronal damage.

DDT and titanium dioxide nanoparticle coexposure induced neurobehavioral deficits in zebrafish.

Both dichlorodiphenyltrichloroethane (DDT) and titanium dioxide nanoparticle (TiO2 NP) have worldwide-scale commercial applications, resulting in their co-pollution in the ecosystems and posing combined health risks. However, there is a lack of toxicity studies for the interactions of DDT and TiO2 NP in the environmental relevant concentrations. In this study, we characterized the coexposures using a zebrafish waterborne exposure approach and evaluated the neurotoxicity response of the treated embryos or adults. Our results showed that DDT/TiO2 NP coexposure enhanced the DDT accumulation in vivo and increased the larval locomotor. The chronic DDT/TiO2 NP coexposure did not affect the overall survival rate, sex ratio and growth. However, DDT/TiO2 NP coexposure severely affected the adult locomotor activity, social contact, shoaling and aggressive behaviors compared to single treatment groups or controls. These adult behavioral deficits were accompanied by changes in neurotransmitter acetylcholine (ACH) level in the brain and muscle tissues, as well as neural development genes expression activation of growth-associated protein 43 (gap43) and synaptic vesicle glycoprotein 2 (sv2) in the brain. The significantly increased ACH level and the activated neural genes expression in the DDT/TiO2 NP co-exposed fish may account for the observed hyperactivity and social deficits.

miRNA-660-3p inhibits malignancy in glioblastoma via negative regulation of APOC1-TGFß2 signaling pathway.

Glioblastoma as the most common and aggressive central nervous system tumor in adults. Its prognosis and therapeutic outcome are poor due to the limited understanding of its molecular mechanism. Apolipoprotein C-1 (APOC1) as a member of the apolipoprotein family that acts as a tumor promoter in various cancers. MicroRNA (miRNA) can silence gene expression and suppress tumor progression. However, the role of APOC1 and its upstream miRNA has not been explored in glioblastoma. Two glioblastoma cell lines (U87 and U251) were used to explore the role of APOC1 and its upstream miRNA-660-3p in glioblastoma tumorigenesis in vitro. Cells with APOC1/miRNA-660-3p overexpression or knockdown were assessed for their proliferation, migration, and invasion in vitro, and tumorigenesis in vivo. Gene and protein expression was assessed by qRT-PCR and western blot, respectively. Cell proliferation was assessed by the MTT assay and the EdU and Ki67 staining. Cell migration and invasion were assessed by the transwell assay. Tumorigenesis in vivo was assessed in U87 cells with a xenograft mouse model. APOC1 was overexpressed in glioblastoma compared with normal peritumoral tissue and was inversely related to patient prognosis. APOC1 overexpression promotes cell proliferation, migration, and invasion in vitro. APOC1 inhibition reduced tumor growth in vivo. miRNA-660-3p inhibits tumorigenesis by directly targeting APOC1. Mechanistically, APOC1 drives the malignancy of glioblastoma by activating the TGFß2 signaling pathway. miRNA-660-3p suppresses tumorigenesis by targeting APOC1. Therefore, miRNA-660-3p/APOC1 axis can serve as potential intervention targets in managing glioblastoma progression.

Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma.

Background: Non-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. It has been reported that CENPE is upregulated in MB, but its role in MB development is still unknown. Methods: We downloaded the relevant RNA seq data and matched clinical information from the GEO database. Bioinformatics analysis includes differential gene expression analysis, Kaplan-Meier survival analysis, nomogram analysis, ROC curve analysis, immune cell infiltration analysis, and gene function enrichment analysis. Moreover, the effects of CENPE expression on cell proliferation, cell cycle, and p53 signaling pathway of non-WNT/non-SHH MB were validated using CENPE specific siRNA in vitro experiments. Results: Compared with normal tissues, CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. The nomogram analysis and ROC curve further confirmed these findings. At the same time, immune cell infiltration analysis showed that CENPE may participate in the immune response and tumor microenvironment (TME) of non-WNT/non-SHH MB. In addition, gene enrichment analysis showed that CENPE was closely related to the cell cycle and p53 pathway in non-WNT/non-SHH MB. In vitro experimental validation showed that knockdown of CENPE inhibited cell proliferation by activating the p53 signaling pathway and blocking the cell cycle. Conclusion: The expression of CENPE in non-WNT/non-SHH MB was positively correlated with poor prognosis. CENPE may affect tumor progression by regulating cell cycle, p53 pathway, and immune infiltration. Hence, CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.

Functional trait space and redundancy of plant communities decrease toward cold temperature at high altitudes in Southwest China.

Plant communities in mountainous areas shift gradually as climatic conditions change with altitude. How trait structure in multivariate space adapts to these varying climates in natural forest stands is unclear. Studying the multivariate functional trait structure and redundancy of tree communities along altitude gradients is crucial to understanding how temperature change affects natural forest stands. In this study, the leaf area, specific leaf area, leaf carbon, nitrogen, and phosphorous content from 1,590 trees were collected and used to construct the functional trait space of 12 plant communities at altitudes ranging from 800 m to 3,800 m across three mountains. Hypervolume overlap was calculated to quantify species trait redundancy per community. First, hypervolumes of species exclusion and full species set were calculated, respectively. Second, the overlap between these two volumes was calculated to obtain hypervolume overlap. Results showed that the functional trait space significantly increased with mean annual temperature toward lower altitudes within and across three mountains, whereas species trait redundancy had different patterns between mountains. Thus, warming can widen functional trait space and alter the redundancy in plant communities. The inconsistent patterns of redundancy between mountains suggest that warming exerts varying influences on different ecosystems. Identification of climate-vulnerable ecosystems is important in the face of global warming.

Autotoxicity of root exudates varies with species identity and soil phosphorus.

Root exudate autotoxicity (i.e. root exudates from a given plant have toxic effects on itself) has been recognized to be widespread. Here we examined how plant species identity and soil phosphorus (P) availability influenced this autotoxicity and the possible stoichiometric mechanisms. We conducted an experiment with three species (Luctuca sativa, Sesbania cannabina, and Solidago canadensis), which were subject to four treatments consisting of activated carbon (AC) and soil P. AC addition increased the whole-plant biomass of each species under high P conditions and this AC effect varied strongly with species identity. For Solidago, the relative increase in whole-plant biomass due to AC addition was larger in the low P than in the high P. Root exudate autotoxicity differed between roots and shoots. AC addition decreased root N:P ratios but failed to influence shoot N:P ratios in three species. These findings suggest that soil P enrichment might mediate root exudate autotoxicity and that this P-mediated autotoxicity might be related to root N and P stoichiometry. These patterns and their implications need to be addressed in the context of plant communities.

Convergent production and tolerance among 107 woody species and divergent production between shrubs and trees.

Green leaves face two fundamental challenges (i.e., carbon fixation and stress tolerance) during their lifespan. However, the relationships between leaf production potential and leaf tolerance potential have not been explicitly tested with a broad range of plant species in the same environment. To do so, we conducted a field investigation based on 107 woody plants grown in a common garden and complementary laboratory measurements. The values, as measured by a chlorophyll meter, were significantly related to the direct measurements of chlorophyll content on a leaf area basis. Area-based chlorophyll content was positively correlated with root surface area, whole-plant biomass, leaf mass per area (LMA), and force to punch. Additionally, LMA had a positive correlation with force to punch. Shrubs had a higher leaf chlorophyll content than trees; however, shrubs and trees exhibited a similar leaf lifespan, force to punch, and LMA. These findings suggest that the production potential of leaves and their tolerance to stresses may be convergent in woody species and that the leaf production potential may differ between shrubs and trees. This study highlights the possibility that functional convergence and divergence might be linked to long-term selection pressures and genetic constraints.

Evidence for enhanced mutualism hypothesis: Solidago canadensis plants from regular soils perform better.

The important roles of plant-soil microbe interactions have been documented in exotic plant invasion, but we know very little about how soil mutualists enhance this process (i.e. enhanced mutualism hypothesis). To test this hypothesis we conducted two greenhouse experiments with Solidago canadensis (hereafter Solidago), an invasive forb from North America, and Stipa bungeana (hereafter Stipa), a native Chinese grass. In a germination experiment, we found soil microbes from the rhizospheres of Solidago and Stipa exhibited much stronger facilitative effects on emergence of Solidago than that of Stipa. In a growth and competition experiment, we found that soil microbes strongly facilitated Solidago to outgrow Stipa, and greatly increased the competitive effects of Solidago on Stipa but decreased the competitive effects of Stipa on Solidago. These findings from two experiments suggest that in situ soil microbes enhance the recruitment potential of Solidago and its ability to outcompete native plants, thereby providing strong evidence for the enhanced mutualism hypothesis. On the other hand, to some extent this outperformance of Solidago in the presence of soil microbes seems to be unbeneficial to control its rapid expansion, particularly in some ranges where this enhanced mutualism dominates over other mechanisms.