The brine depth of the Khorat Basin in Thailand as indicated by high-resolution Br profile.

Bromine contents of a 17-cm halite core from drilling hole of K203 in the Khorat Basin were analysed at 1 cm intervals (17 samples in total). The Br contents range from 99 to 184 ppm with a rapid variation. The K/Mg ratios of halite samples are tens of times higher than those of primary halite fluid inclusions. There is no positive correlation between Mg and Br contents, suggesting that fluid inclusions impose very little or negligible influence on Br contents of halites. The Br contents are not controlled by potash minerals either because the SEM examination shows no potash minerals and there is no relationship between K and Br contents. The Br contents of halite are thus primarily controlled by the Br concentrations of parent brines. The rapid variation of Br contents of halite within this section suggests a shallow saline pan wherein the giant Khorat evaporites were formed. This is contradictory to previous Br profiles of the Lower Salt Member which showed relatively stable and continuously increasing trends. The shallow saline pan model evidenced by high-resolution Br profile is consistent with sedimentary facies and salt mineral textures.

Major and trace-element geochemistry of Late Cretaceous clastic rocks in the Jitai Basin, southeast China.

Major, trace and rare earth element (REE) geochemistry of the late Cretaceous lower Zhoutian Formation from the Jitai Basin of Southeast China were measured by inductively coupled plasma mass spectrometry (ICP-MS) analysis to infer the provenance of the sediments and to reconstruct the palaeoenvironment and palaeoclimate. The wide range of Sr/Cu ratios point to a fluctuating palaeoclimate, and the negative correlation between the FeO/MnO and Al2O3/MgO ratios and the Sr/Cu ratio indicates that the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin can be divided into two parts. The lower part experienced two cooling periods, whilst the upper part was dominated by warm-humid climate. Mostly corresponding trends of the B/Ga, Sr/Ba and Sr/Cu ratios show that the salinity changed consistently with the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin. During the lower part, the salinity changed from salt water to fresh/brackish water. In the upper part, water was mainly fresh/brackish, and there were many changes from fresh/brackish water to salt water. The relatively stable Ni/Co, V/Cr, V/(V + Ni) and Ce/Ce* data indicate a long period of oxic conditions. The La-Th-Sc, Th-Sc-Zr/10 and La/Th-Hf data of the silt- and sandstones of the lower Zhoutian Formation show that its provenance was mainly a mixture of felsic upper crust sediments and older sedimentary rocks.

Nanosystem Integrated with Photosensitizer and Novel Targeting Chemotherapy Agent for Gastric Cancer Chemo-Photodynamic Combined Therapy.

The poor cell membrane penetration ability of photosensitizers resulted in the limited antitumor effect, thereby hampered their potential in clinical translation. The high toxic side effect and multidrug resistance of chemotherapeutic agents during in clinical chemical therapy should be resolved. Nanosystem integrated with photosensitizer and novel targeting chemotherapy agent may be an effective strategy for overcoming clinical or preclinical drawbacks of monotherapy and enhancing therapeutic effect. Therefore, a nanosized micelle F127 integrated with Apogossypolone (ApoG2) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) (referred as F127-ApoG2@AlPcS4) was synthesized to induce the cell death quickly for reducing the risk of resistance and enhancing gastric cancer therapeutic efficiency by combining AlPcS4/photodynamic therapy and ApoG2/chemotherapy. Hydrophobic of ApoG2 and hydrophilic of AlPcS4 self-assembled into this micelle to formation of core-shell structure based on the amphiphilic character of F127 micelle. The reactive oxygen species-dependent mitochondria membrane permeability was improved effectively because of reactive oxygen species generation of ApoG2, thereby resulting in a considerable amount of AlPcS4 and ApoG2 entering the mitochondrial. The AlPcS4 binding site was altered from the cytoplasm to the cell nucleus at higher concentration because of the existence of ApoG2. With irradiation, ApoG2 and AlPcS4 showed effective synergistic anti-tumor effect through inducing apoptosis due to singlet oxygen production regulated mainly by AlPcS4, reactive oxygen species accumulation and calcium overload regulated mainly by ApoG2. Intranuclear AlPcS4 caused cell death through necrosis. The apoptosis induced by AlPcS4 was earlier than ApoG2. In summary, F127-ApoG2@AlPcS4 quickly induced a long-lasting apoptosis that led to cell death, which could be a promising nanosized reagent for gastric cancer therapy based on chemo-photodynamic combined therapy.

Comparison of the synergistic anticancer activity of AlPcS4 photodynamic therapy in combination with different low­dose chemotherapeutic agents on gastric cancer cells.

Limited cellular delivery and internalization efficiency of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) induce poor penetration ability in cells and a slight photodynamic therapy (PDT) effect on gastric cancer. The combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents may provide a promising treatment strategy to increase the weak delivery efficiency of AlPcS4, reducing the dose of chemical agents without reducing efficacy, and improving apoptosis­inducing abilities, thereby increasing the antitumor effects and decreasing the noxious side effects on gastric cancer. We investigated and compared the synergistic antitumor growth effect on gastric cancer cells by combining AlPcS4/PDT treatment with different low­dose chemotherapeutic agents, namely, 5­fluorouracil (5­FU), doxorubicin (DOX), cisplatin (CDDP), mitomycin C (MMC), and vincristine (VCR). The inhibitory effect was increased in treatments that combined AlPcS4/PDT with all the aforementioned low­dose chemotherapeutic agents, to a different extent. An evident synergistic effect was obtained in the combination treatment of AlPcS4/PDT with low­dose 5­FU, DOX, and MMC by increasing AlPcS4 intracellular uptake ability, improving apoptosis­inducing abilities, and prolonging apoptosis­inducing time. The low­dose chemotherapeutic agents prolonged the apoptosis­inducing period of AlPcS4/PDT, and AlPcS4/PDT quickly improved apoptosis­inducing abilities of chemotherapy even at low doses. Generally, the combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents had significant antitumor growth effects in addition to a low dark­cytotoxicity effect on gastric cancer, thereby representing an effective and feasible therapy method for gastric cancer.

AlPcS4-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic® F127 nanomicellar drug carriers.

PURPOSE: As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS4/PDT effect, the AlPcS4 delivery sys tems with different drug carriers were synthesized and investigated. MATERIALS AND METHODS: Gold nanorods, cationic liposomes, and Pluronic® F127 nanomicellars were used to formulate the AlPcS4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca2+]i) concentration were further measured to evaluate the mechanism of cell death. RESULTS: The series of synthesized AlPcS4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS4 delivery efficiency and ability to block serum albumin. In addition, AlPcS4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS4 is used for prolonged gastric cancer therapy. CONCLUSION: The described AlPcS4 drug delivery systems provide promising agents for gastric cancer therapy.

Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms.

The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1(NHAA). The BF1(NHAA) protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1(NHAA) protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

FoxG1 haploinsufficiency results in impaired neurogenesis in the postnatal hippocampus and contextual memory deficits.

FoxG1 (formerly BF-1) encodes a transcription factor that regulates neurogenesis in the embryonic telencephalon. The current study suggests that FoxG1 also regulates neurogenesis in the postnatal hippocampus. FoxG1 continues to be strongly expressed in areas of known postnatal neurogenesis, including the subventricular zone of the lateral ventricle and the dentate gyrus (DG) of the hippocampus. Remarkably, FoxG1+/- mice have a 60% decrease in the total number of hippocampal dentate granule cells that is related to a loss of DG neurogenesis. Comparison of acute and chronic BrdU labeling, and PSA-NCAM staining suggests that the stage at which this loss of neurogenesis occurs progresses with age. Juvenile mice FoxG1+/- primarily show failed apparent survival of postnatally born DG neurons, whereas adult FoxG1+/- mice also show impairment of proliferation and initial DG neuron differentiation. Consistent with this process predominantly affecting postnatal hippocampal neurogenesis, BrdU pulses at embryonic days 16, 17, and 18 labels a higher percentage of DG cells in 6-week-old FoxG1+/- mice than in littermate controls. In contrast to the marked effect of FoxG1 haploinsufficiency on postnatal hippocampal neurogenesis, postnatal neurogenesis of olfactory bulb interneurons is grossly unaffected. Behaviorally, FoxG1+/- mice show hyperlocomotion and impaired habituation in the open field, and a severe deficit in contextual fear conditioning that are suggestive of impaired hippocampal function. Although mechanistic connections between FoxG1 haploinsufficiency and either failed postnatal DG neurogenesis or the behavioral deficits remain to be elucidated, these results present a new model system for impaired postnatal neurogenesis in the DG of adult mice.

Foxg1 suppresses early cortical cell fate.

During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, we observed an excess of Cajal-Retzius neuron production in the cortex. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost.

Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.

FoxO Forkhead transcription factors are shown here to act as signal transducers at the confluence of Smad, PI3K, and FoxG1 pathways. Smad proteins activated by TGF-beta form a complex with FoxO proteins to turn on the growth inhibitory gene p21Cip1. This process is negatively controlled by the PI3K pathway, a known inhibitor of FoxO localization in the nucleus, and by the telencephalic development factor FoxG1, which we show binds to FoxO-Smad complexes and blocks p21Cip1 expression. We suggest that the activity of this network confers resistance to TGF-beta-mediated cytostasis during the development of the telencephalic neuroepithelium and in glioblastoma brain tumor cells.