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Benzimidazole-2-carbamates (BZ, e.g., albendazole; ALB), which bind β-tubulin to disrupt microtubule polymerization, are one of two primary compound classes used to treat giardiasis. In most parasitic nematodes and fungi, BZ-resistance is caused by β-tubulin mutations and its molecular mode of action (MOA) is well studied. In contrast, in Giardia duodenalis BZ MOA or resistance is less well understood, may involve target-specific and broader impacts including cellular damage and oxidative stress, and its underlying cause is not clearly determined. Previously, we identified acquisition of a single nucleotide polymorphism, E198K, in β-tubulin in ALB-resistant (ALB-R) G. duodenalis WB-1B relative to ALB-sensitive (ALB-S) parental controls. E198K is linked to BZ-resistance in fungi and its allelic frequency correlated with the magnitude of BZ-resistance in G. duodenalis WB-1B. Here, we undertook detailed transcriptomic comparisons of these ALB-S and ALB-R G. duodenalis WB-1B cultures. The primary transcriptional changes with ALB-R in G. duodenalis WB-1B indicated increased protein degradation and turnover, and up-regulation of tubulin, and related genes, associated with the adhesive disc and basal bodies. These findings are consistent with previous observations noting focused disintegration of the disc and associated structures in Giardia duodenalis upon ALB exposure. We also saw transcriptional changes with ALB-R in G. duodenalis WB-1B consistent with prior observations of a shift from glycolysis to arginine metabolism for ATP production and possible changes to aspects of the vesicular trafficking system that require further investigation. Finally, we saw mixed transcriptional changes associated with DNA repair and oxidative stress responses in the G. duodenalis WB-1B line. These changes may be indicative of a role for H(2)O(2) degradation in ALB-R, as has been observed in other G. duodenalis cell cultures. However, they were below the transcriptional fold-change threshold (log(2)FC > 1) typically employed in transcriptomic analyses and appear to be contradicted in ALB-R G. duodenalis WB-1B by down-regulation of the NAD scavenging and conversion pathways required to support these stress pathways and up-regulation of many highly oxidation sensitive iron-sulphur (FeS) cluster based metabolic enzymes.

Patient-derived xenograft (PDX) models are more faithful in maintaining the characteristics of human tumors than cell lines and are widely used in drug development, although they have some disadvantages, including their relative low success rate, long turn-around time, and high costs. The collagen gel droplet embedded culture drug sensitivity test (CD-DST) has been used as an

In rheumatoid arthritis (RA), imbalanced T cells subsets play a critical role in sustaining chronic inflammatory responses in the synovium. Naive T cells in RA patients undergo maldifferentiation, including an increase in the effector Th1/Th17 lineage and a reduction in regulatory T (Treg) cells. Upon stimulation, naive CD4+CD45RO- T cells from RA patients exhibited insufficient expression of Foxp3, which induced a deficiency in Tregs production and an imbalance of Treg/Th17 differentiation. Further mechanistic study indicated that RA T cells failed to produce sufficient levels of the histone acetyltransferase Tip60, leading to reduced acetylation of Foxp3; this, in turn, decreased Foxp3 expression, impaired Treg commitment, and promoted Th17 production. Moreover, in human synovium chimeric mice, suppression of Tip60 activity in healthy T cells promoted tissue infiltration and arthritogenesis, while reconstitution of Tip60 in RA T cells suppressed synovitis and effector T cell infiltration. Our findings link T cell maldifferentiation and tissue infiltration with Tip60-mediated Foxp3 acetylation and identify Tip60 as a potential therapeutic target for suppression of tissue inflammation and autoimmunogenesis in RA.

All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. In yeast, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Using a transgenic mouse system called "ICE" (for Inducible Changes to the Epigenome), we show that the process of repairing non-mutagenic DNA breaks accelerates age-related physiological, cognitive, and molecular changes, including the erosion of the epigenetic landscape, a loss of cellular identity, cellular senescence and advancement of the epigenetic clock. Epigenetic reprogramming through ectopic expression of Oct4, Sox2 and Klf4 (OSK) restores patterns of youthful gene expression. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.

Nowadays, risk factors of triple-negative breast cancer (TNBC) metastasis are not well identified. Our present study reveals that an industrial chemical, bisphenol S (BPS), can promote the migration, but not the proliferation, of TNBC cells in vitro. BPS activates YAP, a key effector of Hippo pathway, by inhibiting its phosphorylation, which promotes YAP nuclear accumulation and up-regulates its downstream genes such as CTGF and ANKRD1. Inhibition of YAP blocks the BPS-triggered cell migration and up-regulation of fibronectin (FN) and vimentin (Vim). BPS rapidly decreases the phosphorylation levels of LATS1 (Ser909) in TNBC cells, which regulates the activation and functions of YAP. Silencing LATS1/2 by siRNA increases BPS-induced dephosphorylation of YAP and extended the half-life of YAP protein. Inhibition of G protein-coupled estrogen receptor 1 (GPER) and its downstream PLCβ/PKC signals attenuate the effects of BPS-induced YAP dephosphorylation and CTGF up-regulation. Targeted inhibition of GPER/YAP inhibits BPS-induced migration of TNBC cells. Collectively, we reveal that GPER/Hippo-YAP signal is involved in BPS-induced migration of TNBC cells.

Several microRNAs (miRNAs) have been closely correlated with the development of hepatocellular carcinoma (HCC). However, the involvement of miR-300 in the development of HCC remains unknown. This study elucidated the potential molecular mechanisms of miR-300 in the modulation of the epithelial-mesenchymal transition (EMT) and invasion of HCC. The expression levels of miR-300 in HCC cells and clinical samples were detected by quantitative real-time PCR and in situ hybridization. The in vitro function of miR-300 in HCC was evaluated using a migration/invasion assay. Quantitative real-time PCR, western blotting, immunofluorescence and immunohistochemistry were used to validate the roles of miR-300 and FAK/PI3K/AKT in EMT progression. A dual-luciferase reporter assay was performed to confirm the target gene. miR-300 was down-regulated in HCC and significantly correlated with a poor prognosis in HCC patients. The down-regulation of miR-300 increased the invasiveness of the HCC cells, and promoted the EMT in both HCC tissues and HCC cells. In contrast, up-regulation of miR-300 led to the opposite results. Ectopic overexpression of miR-300 reversed TGF-β1-induced EMT in SMMC-7721 cells, and according to a dual-luciferase reporter assay and rescue assay, miR-300 inhibits the EMT-mediated migration and invasion of HCC cells via the targeted modulation of FAK and the downstream PI3K/AKT signaling pathway. miR-300 targeting modulates FAK, and the PI3K/AKT signaling pathway inhibits the EMT and suppresses the migration and invasion of HCC cells. Thus, miR-300 represents a promising therapeutic target for HCC.

A comprehensive study was performed to identify the origins of salinity and the geochemical processes governing hydrochemistry, and to distinguish the role of evaporation, mixing, and water–rock interaction from seawater intrusion (SWI) or palaeo-saltwater intrusion (PSWI) on groundwater chemistry in the coastal aquifer around the Bohai sea in China. For these purpose, geochemical and multivariate statistical methods were applied. The results indicated that the intrusion area around the Bohai sea can be divided into: (i) the palaeo-saltwater intrusion zone (including the south of Laizhou Bay, Tianjin, and Panjin on the north of Liaodong Bay), and (ii) the modern seawater intrusion zone. The analysis of selected ions (Na+/Cl− and Br−/Cl−) and isotopic compositions showed that the saltwater intrusion is the predominant factor of increasing salinity in groundwater, followed by water–rock interaction (e.g. mineral weathering and ion exchange), and evaporation. Sources of specific ions (Ca and F) are dominated by mineral weathering-dissolution rather than the saltwater intrusion. Furthermore, anthropogenic activities are the dominant cause of groundwater nitrate pollution in the coastal area around Bohai sea. This type of pollution is most serious in Liaodong Bay due to the industrial waste, fertilizers, pesticides, and domestic sewage. It is followed by pollution in Qinhuangdao due to agricultural and domestic factors, and pollution in Laizhou Bay due to domestic sewage. The source of high fluorine in groundwater is the dissolution of fluorine-containing minerals caused by saltwater intrusion. The degree of groundwater fluorine pollution is as follows: Liaodong Bay

A numerical analysis was conducted on the hydrodynamic characteristics of a deep-sea mining vehicle. The simulations employed the Reynolds Stress Model (RSM) to focus on the complicated flow field under three typical motions. During the traveling process, the fluid separated around the vehicle, and the low-pressure areas formed behind the vehicle. The turbulent kinetic energy was large near the shape edge of the vehicle and transferred downstream along with the flow. With the increase of the velocity Reynolds number, the surface friction coefficient increased and the pressure coefficient decreased, which made a large frictional resistance and differential pressure resistance. Meanwhile, although the development processes of the flow field were similar in different motions, the spatial hydrodynamic distributions and the changes of the hydrodynamic coefficients also performed differently. This study can serve as an important reference for the structure optimization and control system development of the mining vehicle.

This paper constructs a prediction model based on Multilayer Perceptron (MLP) to explore the formation mechanism of brine (seawater evaporation or freezing). Four brine sets are extracted from the published, real-world data, and the simulation test with the same six chemical substance features. After integrated comparative experiments on six evaluation metrics, the results show that this model outperforms the other baseline prediction algorithms, achieving the highest precision 0.9625 and at least 8.45% improvement. Furthermore, for predicting the real-world test set, the results confirm the existence of freezing brine for the first time in Laizhou Bay area, China. This model is also used to analyze the mixed simulation results for brine and fresh groundwater. The experimental results indicate that only two out of twenty-nine samples of various concentrations change formation mechanisms after mixing. Overall, the model can effectively distinguish the evaporation and freezing brine, and discover the seawater concentration pathway.

Highlights • ZOSL-1 was the first report that isolated directly from lung metastases of OS. • ZOSL-1 cells were highly metastatic, and the lung metastasis rate was 100% in vivo. • ZOSL-1 cells were high expression in GNAS, SCARB1 and CXCR4 genes., OS (Osteosarcoma) is the most common malignant tumor in adolescents, and lung metastasis limits its therapeutic outcome. The present study aimed to establish a highly metastatic human OS cell line directly from lung metastases and characterize its biological functions. In this study, epithelioid tumor cells with large nucleo-cytoplasmic ratio and abundant organelles were obtained by the tissue mass adherent and repeated digestion adherent method and named ZOSL-1 cells. ZOSL-1 cells had the potential to proliferate in vitro with a doubling time of 39.28 ± 3.04 h and migrate with or without a matrix. ZOSL-1 cells were tumorigenic in vivo, and had the ability to develop lung metastasis after intratibial injection. ZOSL-1 cells expressed the osteogenic-related genes osteocalcin and osteopontin. In addition, the expression of ZOSL-1 in Fas cell surface death receptor (FAS), CD44 molecule (CD44), GNAS complex locus (GNAS), scavenger receptor class B member 1 (SCARB1), C-X-C motif chemokine receptor 4 (CXCR4), cadherin 11 (CDH11), neurofibromin 2 (NF2) and ezrin (EZR) genes may be related to its transfer efficiency. Taken together, these results indicated the high metastatic capability and important biological functions of ZOSL-1 cells. ZOSL-1 establishment provided a relevant model for the study of osteosarcoma lung metastasis.

Two novel Zn(II)/Cd(II) coordination polymers (CPs), {[Zn(L)(DCTP)]·H2O}n (1) and [Cd2(L)(DCTP)2]n (2) (H2DCTP ​= ​2,5-dichloroterephthalic acid, L ​= ​1,3-bis(1-(pyridin-3-ylmethyl)-1H-benzo[d]imidazole-2-yl)propane) were successfully synthesized and characterized. The structure of 1 was formed by a 1D V-like chains and further packed a 2D supramolecular network through hydrogen bonding interactions. The structure of 2 featured an uncommon 3D lattice with the Schlafli symbol of {4.62.72.8}{4.62.73}2{42.62.7.8}. 1 and 2 displayed high thermostability and water-stability (pH ​= ​3–12). Furthermore, based on luminescence quenching, both CPs 1 and 2 are the first report of fluorescent CPs from L ligand for the detection of acetylacetone and Fe3+ ions, with the merits of great efficiency, anti-interference and recyclability abilities.

This paper proposes a novel underdetermined blind source separation (UBSS) method based on short-time Fourier transform (STFT) to separate non-stationary sources. This method relaxes the premise in the subspace algorithm presented by Aissa-El-Bey et al. and allows that the number of active sources is no more than that of sensors by exploiting the statistic characteristic of sources and sparsity of non-stationary signals in time–frequency (TF) domain simultaneously. It first estimates the indexes of active sources in TF domain accurately by calculating the average power of sources at every TF point (except the point with the trivial energy contribution) and then obtains the estimation of source STFT by pseudo-inversion operator, which can avoid calculating the eigenvalue of covariance matrix of the mixtures and seeking the minimum of the object function based on subspace projection. Thus, the proposed algorithm has low computational cost and high separation quality. Simulation results validate the superiority of the proposed algorithm in comparison with the existing subspace-based algorithms.

Background/Aims Mitogen- and stress-activated protein kinase 1 (MSK1) has recently been implicated in cell proliferation and neoplastic transformation. However, the involvement of MSK1 in colorectal cancer (CRC) has not been addressed. This study aimed to evaluate the expression and potential functions of MSK1 in CRC. Methods The MSK1 expression was investigated by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. The associations between clinicopathological characteristics and MSK1 expression were assessed. Kaplan–Meier analysis and Cox regression models were carried out. CRC cells with MSK1 knockdown or overexpression were generated. A range of experiments were performed to demonstrate MSK1’s role in CRC. Results MSK1 was overexpressed in 148 out of 329 CRC patients. CRC patients with high MSK1 expression had shorter overall survival than those with low MSK1 (P = 0.033), especially among patients with stage III tumors (P = 0.005). Knockdown of MSK1 in CRC cells suppressed cell proliferation, anchorage-independent growth, migration and invasion, and promoted 5-fluorouracil chemosensitivity and intracellular NADP+/NADPH ratio. However, overexpression of MSK1 had the opposite effects. Conclusions Overexpression of MSK1 is associated with poor prognosis in CRC and is connected to tumor aggressiveness. MSK1 is a potential target for new therapies and a candidate of biomarker for prognosis.

Triple-negative breast cancer (TNBC) is characterized by high vascularity and frequent metastasis. Here, we found that activation of G protein-coupled estrogen receptor (GPER) by its specific agonist G-1 can significantly inhibit interleukin 6 (IL-6) and vascular endothelial growth factor A (VEGF-A). TNBC tissue microarrays from 100 TNBC patients revealed GPER is negatively associated with IL-6 levels and higher grade and stage. Activation of GPER or anti-IL-6 antibody can inhibit both in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and migration of TNBC cells. While recombinant IL-6 supplementary can significantly reverse the inhibitory effects of G-1, suggesting the essential role of IL-6 in G-1 induced suppression of angiogenesis and invasiveness of TNBC cells. G-1 treatment decreased the phosphorylation, nuclear localization, transcriptional activities of NF-κB and suppressed its binding with IL-6 promoter. BAY11-7028, the inhibitor of NF-κB, can mimic the effect of G-1 to suppression of IL-6 and VEGF-A. While over expression of p65 can attenuate the inhibitory effects of G-1 on IL-6 and VEGF expression. The suppression of IL-6 by G-1 can further inhibit HIF-1α and STAT3 signals in TNBC cells by inhibition their expression, phosphorylation and/or nuclear localization. Moreover, G-1 also inhibited the in vivo NF-κB/IL-6 signals and angiogenesis and metastasis of MDA-MB-231 xenograft tumors. In conclusion, our study demonstrated that activation of GPER can suppress migration and angiogenesis of TNBC via inhibition of NF-κB/IL-6 signals, therefore it maybe act as an important target for TNBC treatment.

SUMMARYAll living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.One Sentence SummaryThe act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging

Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract diseases with limited therapeutic strategies and poor prognosis. Various therapeutic agents have been demonstrated effective in preclinical models, but high dose requirement and toxicity to normal cells limit their clinical applications. Considering the high concentration of glutathione (GSH) in GBC, we developed a GSH-responsive nanoparticle (NP) system based on biodegradable poly(disulfide amide) (Cys-8E Polymer) for targeted delivery of a BRD4 inhibitor (JQ1), which is known as a promising therapeutic agent for GBC treatment. JQ1-loaded Cys-8E nanoparticles (JQ1@Cys-8E NPs) possessed a high JQ1 loading, preferable stability and redox-responsive release behavior. Additionally, the NPs showed good targeted delivery into GBC tumor spheroids and GBC patient-derived xenograft (PDX) tumors. Specifically, the intracellular GSH in tumors could trigger the release of JQ1, which induced the cell cycle arrest and apoptosis of GBC cells. RNA-sequencing analysis revealed that JQ1@Cys-8E NPs enhanced the effect of JQ1 through inhibiting NF-κB pathway. Importantly, JQ1@Cys-8E NPs significantly suppressed GBC tumor growth in the PDX model of early recurrence. No obvious systemic toxicity and organ damages were observed after treatment with JQ1@Cys-8E NPs. Our results demonstrate the promising therapeutic applications of JQ1@Cys-8E NPs for adjuvant therapy in GBC treatment.

Mobility and controllability of a deep ocean mining vehicle directly determine its operational efficiency and safety. In this study, the spatial hydrodynamic distributions acting on a mining vehicle under different motion states were ascertained through the computational fluid dynamics (CFD) numerical simulations. Then, a new multi-body dynamic (MBD) model of the vehicle integrated with its hydrodynamic effects and vehicle-sediment mechanics interaction was established. An underwater test of a tracked prototype vehicle in a large-scale laboratory water tank was performed and validated the feasibility and accuracy of the new MBD model. Furthermore, a controller based on a fuzzy self-adaptive PID method for the predetermined trajectory tracking of the mining vehicle was designed and modelled. Finally, the real-time information exchange and collaborative simulation between the developed MBD model and the controller were realized and proved that the proposed motion controller had a satisfactory performance in the trajectory tracking control for deep ocean mining vehicles.

Coastal zones are the most sensitive and vulnerable ecological environments in the world. Submarine groundwater discharge (SGD) is an important pathway for material transport between land and sea in the low-lying coastal plains of coastal zones. In the present study, electrical resistivity tomography was used to monitor submarine groundwater discharge in the intertidal zone. The salinity change ratio was derived using Archie's law and Manheim's equation, and was used as an index to describe the dynamic discharge process. A model of the seawater circulation process in the multilayer coastal aquifer system was established. The model contains a window area between the upper unconfined and lower confined aquifer, and a highly permeable channel in the upper silt layer. The results of the study provide a theoretical basis and technical support for the rapid assessment of SGD in low-lying coastal plains, and will assist in the management of coastal zone environments.

Fibre strength (FS) is an important quality attribute in the modern textile industry, which is genetically controlled by quantitative trait loci (QTLs). Fine-mapping stable QTLs for FS to identify candidate genes would be valuable for uncovering the genetic basis of fibre quality traits in cotton. Here, a single segment introgression line, IL-D2−2, from the cross of (TM-1×TX-1046) reported in our previous studies, was found to have significantly improved FS compared with the recurrent parent TM-1. To fine-map the QTLs of the FS, we further crossed IL-D2−2 with its recurrent parent TM-1 to produce F2 and F2:3 populations. QTL analysis and substitution mapping showed qFS-Chr. D02 was anchored into a 550.66 kb-interval between two markers, INTR1027 and JESPR-231. This interval contained 67 genes, among which 27 genes related to cell-wall synthesis were selected to conduct qRT-PCR. The results revealed seven genes were expressed significantly differently during the fibre secondary-wall-thickening stage (10–25 days post-anthesis), three being upregulated and four downregulated in IL-D2−2. Both GH_D02G2269 (UDP-glucosyl transferase 84B1) and GH_D02G2289 (unknown function (DUF869)) with nonsynonymous SNPs in IL-D2−2 had significantly downregulated expression, suggesting they were candidates for qFS-Chr. D02. This research provides information about marker-assisted selection for cotton fibre strength improvement.

In recent years, Thailand and Bangladesh have been drawing more attention due to groundwater pollution, but there is rarely a comparative study on hydrochemical evolution and quality assessment of groundwater in the areas In this paper, end-member mixing and Gibbs model are used to study the evolution of groundwater hydrochemistry based on the 74 water samples. Due to the seawater intrusion, the evolution path of groundwater in Bangkok Bay is Ca/Mg-HCO3 → Na (Ca/Mg)-HCO3 and Na (Ca/Mg)-Cl → Na-Cl, which led to increased Na+, K+, and HCO3– concentrations in groundwater and enrichment of fluorine in groundwater caused fluorine pollution. In contrast, although the evolution path of groundwater in southern Bangladesh shows a similar pattern as Ca/Mg-HCO3 → Na (Ca/Mg)-HCO3 and Ca/Mg-Cl → Na-Cl, the principal influence factors are residential, agricultural and industrial pollutants. The scope of seawater intrusion is only limited to estuary areas of the southern estuary, whereas most groundwater is received recharge of polluted surface water, which resulted in the enrichment of Fe and Mn. In addition, compared with shallow groundwater, deep groundwater is updated slowly and evolved to higher degree, and is in the Na (Ca/Mg)-HCO3 and Ca/Mg-Cl stage. For improving groundwater conditions in southern Bangladesh, enhancing the supply capacity of surface potable water and significantly reducing groundwater exploitation are priority. Strictly controlling the generation, storage and treatment of domestic waste, industrial and agricultural pollutants are also important. In Bangkok Bay, reducing the groundwater exploitation and dispersing the exploitation area is required.

PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell (LSC) determination during eye development. Defects in Pax6 cause aniridia and LSC deficiency in humans and the Sey (Small eye) phenotype in mice (Massé, K., Bhamra, S., Eason, R., Dale, N., and Jones, E. A. (2007) Nature 449, 1058-1062). However, how PAX6 specifies LSC and corneal fates during eye development is not well understood. Here, we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, p63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors and later in LSCs. Using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs led to up-regulation of skin epidermis-specific keratins concomitant with differentiation to a skin fate. Using gene expression analysis, we identified the involvement of Notch, Wnt, and TGF-β signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in the keratin gene expression profile and by the appearance of congenital dermoid tissue.

Asian marginal seas play an important role in moderating material and energy flux linkages between Asia and the Northwest Pacific, and thus have profound climatic and environmental effects. In this study, by combining paleomagnetic study with sediment grain-size analysis on the Lz908 borehole sedimentary sequence from the southern Bohai Sea, new insights into regional geomorphological process since the late early Pleistocene are obtained. The main results are as follows. (1) Paleomagnetic findings suggest that the sequence recorded the Brunhes normal chron and the late Matuyama reverse chron, including the Jaramillo normal subchron. (2) The sedimentary processes in the study area since 1327 ka show a three-stage pattern, with depositional rates of 4.3, 17 and 107 cm/ka during 1327–260 ka (later part of the early and middle Pleistocene), 260–10 ka (late middle and late Pleistocene), and the Holocene, respectively. (3) The sedimentary basin was a part of the Bohai Paleolakes (BHPL) prior to 260 ka, whose water levels were consistently higher than 3 m above the present-day level. After 260 ka, seawater entered the Bohai basin, and relative sea level cyclically fluctuated with global sea-level changes. We therefore infer that the Miaodao Islands, which were the natural barrier of the BHPL blocking seawater entry, had partially subsided before 260 ka, only allowing seawater to enter the basin during a global sea-level maximum. The BHPL terminated around 260 ka, and the “barrier” subsided completely around ~ 130 ka, causing the Bohai basin to become an inner shelf sea.

Background Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study. Methods We utilized proteomic study to indentify the protein expression changes of Sertoli TM4 cells treated with 10− 8 M and 10− 5 M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis. Results Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10− 8 M and 10− 5 M BPA, respectively, for 24 h. Exposure to 10− 5 M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10− 8 M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages. Conclusions Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism. General significance Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.

We reported a large-scale synthesis of nanocrystals of BaTiO 3 , SrTiO 3 , PbTiO 3 , Sr x Ba 1− x TiO 3 through low-temperature and solution-phase processes without any surfactant. The series of samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Samples obtained were of high purity, consisting of nanoparticles with fine crystallinity and uniformity as well as good dispersibility in ethanol. This method might also offer an effectively new way to synthesis other titanate nanocrystals with perovskite structure in the future.

The pollen-tube pathway is feasible to transform vector- and selectable marker-free linear gene cassettes into plants to address the biosafety issues. However, its transformation frequency is low and the screening of selectable marker-free transformants by PCR analysis is time-consuming and expensive. In this study, a linear GFP cassette (Ubi-GFP-nos) flanked by 25bp T-DNA borders was transformed into maize via the pollen-tube pathway. The forepart of each maize ear was divided into five segments (segments I-V) at an interval of two rows of kernels. The segments that were most likely to contain transgenic kernels were identified by monitoring GFP expression in the immature embryos. A total of 21 ears were transformed with the linear GFP cassette. Seven out of 19 ears exhibited positive GFP expression in the immature embryos. Transgenic kernels were primarily identified in segments III and IV. A total of 121 plants derived from kernels located within segments III and IV of the remaining two ears were screened by PCR analysis. Six plants (4.96%) showed the presence of the GFP cassette. Southern blot analysis showed that the transgenic plants had simple integration patterns. The identification of transgenic kernels would facilitate PCR screening for marker-free transgenic plants.

Plant vacuolar Na(+)/H(+) antiporter plays an important role in salt tolerance. In order to understand the molecular basis of vacuolar Na(+)/H(+) antiporter responded to salinity and reveal a possible role of salt tolerance in monocots, a vacuolar Na(+)/H(+) antiporter gene (AlNHX) was isolated by reverse transcription-PCR and RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) based on the homology from Aeluropus littoralis (Gouan) Parl, a graminaceous halophyte. The AlNHX sequence contained 2706bp with an open read frame of 1623bp and the deduced transcripts encoding 540 amino acids shared a high homology with those putative vacuolar Na(+)/H(+) antiporters of higher plants. AlNHX was predicted containing ten putative hydrophobic regions, which was different with AtNHX1 and OsNHX1. DNA gel blot analysis indicated that there were two or three copies of AlNHX in the A. littoralis genome. The increased transcript levels of AlNHX were much higher in roots than that in shoots under salt stress. In addition, overexpression of AlNHX in tobacco conferred high salt tolerance to the transgenic plants. The analysis of ion contents indicated that under high salt stress for one month, the transgenic plants compartmentalized more Na(+) in the roots and kept a relative high K(+)/Na(+) ratio in the leaves compared with wild-type plants.