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Accumulating evidence indicates that mammalian target of rapamycin (mTOR) exerts a crucial role in aerobic glycolysis and tumorigenesis, but the underlying mechanisms remain largely obscure. Results from Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs) and human cancer cell lines consistently indicate that the expression of glucose transporter 3 (Glut3) is dramatically up-regulated by mTOR. The rapamycin-sensitive mTOR complex 1 (mTORC1), but not the rapamycin-insensitive mTOR complex 2 (mTORC2), was involved in the regulation of Glut3 expression. Moreover, mTORC1 enhances Glut3 expression through the activation of the IKK/NFκB pathway. Depletion of Glut3 led to the suppression of aerobic glycolysis, the inhibition of cell proliferation and colony formation, and the attenuation of the tumorigenic potential of the cells with aberrantly hyper-activated mTORC1 signaling in nude mice. We conclude that Glut3 is a downstream target of mTORC1, and it is critical for oncogenic mTORC1-mediated aerobic glycolysis and tumorigenesis. Hence Glut3 may be a potential target for therapy against cancers caused by the aberrantly activated mTORC1 signaling. [ABSTRACT FROM AUTHOR]

The shale oil reservoir of the Lucaogou Formation in the Jimsar Sag has undergone tectonic movement, regional deposition and complex diagenesis processes. Therefore, various reservoir space types and complex combination patterns of pores have developed, resulting in an intricate pore throat structure. The complex pore throat structure brings great challenges to the classification and evaluation of reservoirs and the efficient development of shale oil. The methods of scanning electron microscopy, high-pressure mercury injection, low-temperature adsorption experiments and thin-slice analysis were used in this study. Mineral, petrology, pore throat structure and evolution process characteristics of the shale oil reservoir were analyzed and discussed qualitatively and quantitatively. Based on these studies, the evolution characteristics and formation mechanisms of different pore throat structures were revealed, and four progressions were made. The reservoir space of the Lucaogou Formation is mainly composed of residual intergranular pores, dissolved pores, intercrystalline pores and fractures. Four types of pore throat structures in the shale oil reservoir of the Lucaogou Formation were quantitatively characterized. Furthermore, the primary pore throat structure was controlled by a sedimentary environment. The pores and throats were reduced and blocked by compaction and cementation, which deteriorates the physical properties of the reservoirs. However, the dissolution of early carbonate, feldspar and tuffaceous minerals and a small amount of carbonate cements by organic acids are the key factors to improve the pore throat structure of the reservoirs. The genetic evolution model of pore throat structures in the shale oil reservoir of the Lucaogou Formation are divided into two types. The large-pore medium-fine throat and medium-pore medium-throat reservoirs are mainly located in the delta front-shallow lake facies and are characterized by the diagenetic assemblage types of weak compaction–weak carbonate cementation–strong dissolution, early medium compaction–medium calcite and dolomite cementation–weak dissolution. The medium-pore fine throats and fine-pore fine throats are mainly developed in shallow lakes and semi-deep lakes. They are characterized by the diagenetic assemblage type of strong compaction–strong calcite cementation–weak dissolution diagenesis. This study provides a comprehensive understanding of the pore throat structure and the genetic mechanism of a complex shale oil reservoir and benefits the exploration and development of shale oil. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback inhibition of Akt. The exact mechanisms of this process are still not fully understood. Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. We demonstrate that STAT3 promotes the transcription of PTEN by directly binding on the PTEN promoter. Elevated PTEN then inhibits the proliferation of Tsc1 −/− or Tsc2 −/− cells through down-regulation of Akt signaling. Activation of PTEN in this pathway may thus serve as a protective mechanism against hyper-activated mTORC1 mediated tumorigenesis and contribute to the benign nature of tumors caused by loss of either TSC1 or TSC2. [Copyright &y& Elsevier]

Abstract: Programmed cell death (PCD) is a crucial process for plants during development and environmental stress. OsPDCD5, is an ortholog to mammalian programmed cell death 5 gene. Here we report that decreased expression of OsPDCD5 caused by antisense technology could induce pollen sterility in photoperiod-sensitive rice. The male sterility of transgenic plants is reversible, determined mainly by photoperiod. Transgenic plants are sterile under long-day photoperiod (≥13.5h sunlight) with postponed heading time, while they can restore fertility under short-day photoperiod (below 13h sunlight). Analysis of tissue sections of anthers displays the tapetum cells of the anther wall retard PCD process in transgenic plants under long-day photoperiod. The retarded PCD was also confirmed by DNA fragmentation. In F1 hybrids made from transgenic plants with antisense-OsPDCD5 and japonica rice varieties, lower transcript inhibition could restore fertility, under certain photoperiod and temperatures. The surprising discovery of the photosensitive male fertility suggested that by using specific photoperiods, the male sterility (PGMS) could be used for commercial production of hybrid rice using a two-line breeding system. The transgenic hybrid strategy was easy to apply, reduced costs and shortened the breeding period. It provides great advantages for commercial applications in rice and other crops. [Copyright &y& Elsevier]

In rice ( Oryza sativa L.), the number of panicles, spikelets per panicle and grain weight are important components of grain yield. These characteristics are controlled by quantitative trait loci (QTLs) and are derived from variation inherent in crops. As a result of the complex genetic basis of these traits, only a few genes involved in their control have been cloned and characterized. We have previously map-cloned a gene cluster including eight leucine-rich repeat receptor-like kinase ( LRK) genes in Dongxiang wild rice ( Oryza rufipogon Griff.), which increased the grain yield by 16%. In the present study, we characterized the LRK1 gene, which was contained in the donor parent (Dongxiang wild rice) genome and absent from the recurrent parent genome (Guichao2, Oryza sativa L. ssp. indica). Our data showed that rice LRK1 is a plasma membrane protein expressed constitutively in leaves, young panicles, roots and culms. The over-expression of rice LRK1 results in increased panicles, spikelets per panicle, weight per grain and enhanced cellular proliferation, leading to a 27.09% increase in total grain yield per plant. The increased number of panicles and spikelets per panicle are associated with increased branch number. Our data suggest that rice LRK1 regulates rice branch number by enhancing cellular proliferation. The functional characterization of rice LRK1 facilitates an understanding of the mechanisms involved in cereal crop yield, and may have utility in improving grain yield in cereal crops. [ABSTRACT FROM AUTHOR]

Background: The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results: ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions: The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors. [ABSTRACT FROM AUTHOR]

Background: Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods: HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Ptenfl/fl mice were inter-crossed to generate WT, HBV, Pten−/− and HBV; Pten−/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73−/− mice were then mated with HBV; Pten−/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results: Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten−/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions: This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration. [ABSTRACT FROM AUTHOR]

China shale oil, which is preserved in lacustrine shale with strong heterogeneity and relatively low maturity, has been a research hotspot of unconventional resources. However, controlling factors of shale oil enrichment and resource potential evaluation restricted efficient exploration and development of lacustrine shale oil. On the basis of well logging data, TOC content, Rock-Eval pyrolysis values, thermal maturity, 100 oil saturation data, and pressure coefficient, the core observation, X-ray diffraction analysis, physical property analysis, scanning electron microscopy, CT scan, well logging interpretation, and volumetric genesis method depending on three-dimensional geological modeling were used to determine enrichment factors and evaluate the resource potential of Qingshankou Formation shale oil in the Southern Songliao Basin. Shale oil was mainly enriched in the semideep and deep lake shale of K2qn1, with the high capacity of hydrocarbon generation and favorable petrological and mineralogical characteristics, pore space characteristics, and physical properties in the low structural part of the Southern Songliao Basin. The three-dimensional geological resource model of Qingshankou Formation lacustrine shale oil was determined by the key parameters (Ro, TOC, and S 1 ) of shale oil in the favorable zone of the Southern Songliao Basin, northeast China. The geological resource of shale oil, which was calculated by two grid computing methods ( F 1 and F 2 ), was, respectively, 1.713 × 10 12 kg and 1.654 × 10 12 kg. The great shale oil resource indicates a promising future in the exploration and development of Qingshankou Formation shale oil of the Southern Songliao Basin. [ABSTRACT FROM AUTHOR]

Background: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. Methods: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. Results: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin–proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. Conclusion: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin–proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression. [ABSTRACT FROM AUTHOR]

China shale oil, which is preserved in lacustrine shale with strong heterogeneity and relatively low maturity, has been a research hotspot of unconventional resources. However, controlling factors of shale oil enrichment and resource potential evaluation restricted efficient exploration and development of lacustrine shale oil. On the basis of well logging data, TOC content, Rock-Eval pyrolysis values, thermal maturity, 100 oil saturation data, and pressure coefficient, the core observation, X-ray diffraction analysis, physical property analysis, scanning electron microscopy, CT scan, well logging interpretation, and volumetric genesis method depending on three-dimensional geological modeling were used to determine enrichment factors and evaluate the resource potential of Qingshankou Formation shale oil in the Southern Songliao Basin. Shale oil was mainly enriched in the semideep and deep lake shale of K2qn1, with the high capacity of hydrocarbon generation and favorable petrological and mineralogical characteristics, pore space characteristics, and physical properties in the low structural part of the Southern Songliao Basin. The three-dimensional geological resource model of Qingshankou Formation lacustrine shale oil was determined by the key parameters (Ro, TOC, and S 1 ) of shale oil in the favorable zone of the Southern Songliao Basin, northeast China. The geological resource of shale oil, which was calculated by two grid computing methods ( F 1 and F 2 ), was, respectively, 1.713 × 10 12 kg and 1.654 × 10 12 kg. The great shale oil resource indicates a promising future in the exploration and development of Qingshankou Formation shale oil of the Southern Songliao Basin. [ABSTRACT FROM AUTHOR]

Background: Aberrantly activated mammalian target of rapamycin complex 1 (mTORC1) plays a vital role in tumor angiogenesis, but its precise mechanisms are still unclear. Methods: Micro-RNA-130b-3p (miR-130b-3p) expression in mTORC1-activated and control cells was examined by quantitative real-time PCR (qRT-PCR). MiR-130b-3p levels and their correlation with mTORC1 activity were evaluated by analyzing publicly available databases and in-house head and neck squamous cell carcinoma (HNSCC) tissues. The role of miR-130b-3p in mTORC1-mediated angiogenesis and tumor growth was examined using tube formation assay, chicken chorioallantoic membrane assay, cell line − derived xenograft models, and an HNSCC patient-derived xenograft (PDX) model. The regulatory mechanisms among signal transducer and activator of transcription 3 (STAT3), miR-130b-3p, and muscleblind-like protein 1 (MBNL1) were investigated via bioinformatics analyses, qRT-PCR, western blot, RNA immunoprecipitation, immunofluorescence, luciferase reporter assay, and chromatin immunoprecipitation assay. Results: Elevated miR-130b-3p enhanced the angiogenic and tumorigenic abilities of mTORC1-activated cells both in vitro and in vivo. STAT3, a downstream effector of mTORC1, transactivated miR-130b-3p by direct binding promoter of the miR-130b gene. MBNL1 was identified as a direct target of miR-130b-3p. MBNL1 depletion rescued the compromised angiogenesis and tumor growth caused by miR-130b-3p inhibition. MiR-130b-3p levels were significantly upregulated and positively correlated with mTORC1 signaling in multiple cancers. MiR-130b-3p inhibition attenuated tumor angiogenesis and growth in an HNSCC PDX model. MBNL1 feedback inhibited STAT3 activation in mTORC1-activated cells. Conclusions: The STAT3/miR-130b-3p/MBNL1 feedback loop plays a vital role in mTORC1-mediated angiogenesis and tumor progression. This pathway could be targeted for therapeutic intervention of mTORC1-related cancers. [ABSTRACT FROM AUTHOR]

The article presents Aberrant mTOR/autophagy/Nurr1 signaling is critical for TSC-associated tumor development. Topics discussed include Tuberous sclerosis complex (TSC), an inherited neurocutaneous disease, is caused by mutations in either the TSC1 or TSC2 gene; and this genetic disorder is characterized by the growth of benign tumors in the brain, kidneys, and other organs.

Pulmonary microvascular endothelium barrier plays a critical role in protecting the pulmonary tissue from inflammatory injury in acute respiratory distress syndrome and acute lung injury (ARDS/ALI). The dysregulation of IQ-GTPase-activating protein 1 (IQGAP1) was an important etiology of endothelium barrier injury. However, significant differentially expressed genes (DEGs) and signaling pathways directly regulated by IQGAP1 are too complicated to fully understand. In this research, we identified a total of 1216 DEGs regulated by knockdown of IQGAP1 in rat pulmonary microvascular endothelial cells on the basis of transcriptomic RNA sequencing (RNA-Seq). Among them, 665 were upregulated DEGs and 551 were downregulated DEGs. Gene ontology analysis has revealed that upregulated DEGs were mainly enriched in DNA replication, cell cycle, and chromosome formation, while downregulated DEGs were mainly involved in the regulation of many cellular bioprocesses including cell proliferation, cell adhesion, and cell migration. Kyoto Encyclopedia of Genes and Genomes pathways analysis toward DEGs showed that upregulated pathways were mainly about DNA replication, while the significantly downregulated pathways were about TNF signaling pathway and some inflammatory- and proliferation-related pathways. Furthermore, we choose 30 DEGs for validation by qRT-PCR, the results were quite consistent with the RNA-Seq. In addition, we also found that knockdown of IQGAP1 caused a significant impact on many cytokines and inflammatory factors, which play a vital role in ARDS/ALI. In summary, in this study on the basis of RNA-Seq, we found IQGAP1 not only exerts a crucial role in microvascular endothelium barrier but also plays an important role in inflammation, which might provide a new insight for future study on IQGAP1 in the related diseases such as ARDS/ALI. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the benign tumor formation in multiple organs. The main etiology of TSC is the loss‐of‐function mutation of TSC1 or TSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). In this research, we found a significant increase of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) expression in Tsc1−/− and Tsc2−/− mouse embryonic fibroblasts (MEFs) compared with the control cells. Inhibition of mTORC1 led to a dramatic decrease of PFKFB3 expression, indicating PFKFB3 regulation by mTORC1. Moreover, suppression of mTORC1 inhibited the expression of PFKFB3 in rat uterine leiomyoma‐derived Tsc2‐null ELT3 cells and human tumor cells. Furthermore, we identified hypoxia‐inducible factor 1α (HIF‐1α) as a mediator transmitting the signal from mTORC1 to PFKFB3. Depletion of PFKFB3 inhibited proliferation and tumorigenicity of Tsc1‐ or Tsc2‐deficient cells. In addition, combination of rapamycin with PFK15, a PFKFB3 inhibitor, exerts a stronger inhibitory effect on cell proliferation of Tsc1‐ or Tsc2‐null MEFs than treatment with single drug. We conclude that loss of TSC1 or TSC2 led to upregulated expression of PFKFB3 through activation of mTORC1/HIF‐1α signaling pathway and co‐administration of rapamycin and PFK15 may be a promising strategy for the treatment of TSC tumors as well as other hyperactivated mTORC1‐related tumors. [ABSTRACT FROM AUTHOR]

Drought represents a key limiting factor of global crop distribution. Receptor-like kinases play major roles in plant development and defence responses against stresses such as drought. In this study, LRK2, which encodes a leucine-rich receptor-like kinase, was cloned and characterized and found to be localized on the plasma membrane in rice. Promoter-GUS analysis revealed strong expression in tiller buds, roots, nodes and anthers. Transgenic plants overexpressing LRK2 exhibited enhanced tolerance to drought stress due to an increased number of lateral roots compared with the wild type at the vegetative stage. Moreover, ectopic expression of LRK2 seedlings resulted in increased tiller development. Yeast two-hybrid screening and bimolecular fluorescence complementation (BiFC) indicated a possible interaction between LRK2 and elongation factor 1 alpha (OsEF1A) in vitro. These results suggest that LRK2 functions as a positive regulator of the drought stress response and tiller development via increased branch development in rice. These findings will aid our understanding of branch regulation in other grasses and support improvements in rice genetics. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditional Chinese Medicine (TCM) has been increasingly used to treat cancers. Trametes robiniophila Murr. (Huaier) is a medicinal fungus for treatment of inflammation and cancer. Huaier Granule has great clinical effect in various types of cancers, including liver cancer, lung cancer, gastric cancer, and breast cancer. Aim of the study The present study was performed to determine the therapeutical effect of Huaier on cancers caused by aberrant mTOR signaling in vitro and in vivo , investigate the combination effect of Huaier and rapamycin or cisplatin on cell viability, and explore its underlying mechanism. Materials and methods The therapeutical effect of Huaier on cancers caused by aberrant mTOR signaling and the underlying mechanism of combination effect of Huaier and rapamycin or cisplatin on cell viability were investigated in mouse embryonic fibroblasts, rat uterine leiomyoma cells, human hepatoma cells, human lung carcinoma cells, and xenograft tumor model by cell viability assay and immunoblotting. Results Activation of mTOR sensitizes cells to Huaier treatment. Huaier inhibits tumorigenic capacity of cells with activated mTOR in vivo . Moreover, activation of mTOR signaling induced by Huaier contributes to the increased sensitivity of cells to rapamycin or cisplatin in response to Huaier treatment. Conclusions Huaier may be a potential drug for the treatment of cancers caused by aberrant mTOR signaling. The combination of Huaier and rapamycin may be a candidate regimen in the treatment of these cancers. [ABSTRACT FROM AUTHOR]

Abstract: Many rice breeding programs have currently reached yield plateaus as a result of limited genetic variability in parental strains. Dongxiang common wild rice (Oryza rufipogon Griff.) is the progenitor of cultivated rice (Oryza sativa L.) and serves as an important gene pool for the genetic improvement of rice cultivars. In this study, heterotic loci (HLs) associated with six yield-related traits were identified in wild and cultivated rice and investigated using a set of 265 introgression lines (ILs) of O. rufipogon Griff. in the background of the Indica high-yielding cultivar Guichao 2 (O. sativa L.). Forty-two HLs were detected by a single point analysis of mid-parent heterosis values from test cross F1 offspring, and 30 (71.5%) of these HLs showed significantly positive effects, consistent with the superiority shown by the F1 test cross population in the six yield-related traits under study. Genetic mapping of hsp11, a locus responsible for the number of spikelets per panicle, confirmed the utility of these HLs. The results indicate that favorable HLs capable of improving agronomic traits are available. The identification of HLs between wild rice and cultivated rice could lead to a new strategy for the application of heterosis in rice breeding. [Copyright &y& Elsevier]

Shale gas accumulates in reservoirs that have favorable characteristics and associated organic geochemistry. The Wufeng-Longmaxi formation of Well Yucan-6 in Southeast Chongqing, SW China was used as a representative example to analyze the organic geochemical and reservoir characteristics of various shale intervals. Total organic carbon (TOC), vitrinite reflectance (Ro), rock pyrolysis, scanning electron microscopy (SEM), and nitrogen adsorption analyses were conducted, and a vertical coupling variation law was established. Results showed the following: the Wufeng-Longmaxi formation shale contains kerogen types I and II2; the average TOC value at the bottom of the formation is 3.04% (and the average value overall is 0.78%); the average Ro value is 1.94%; the organic matter is in a post mature thermal evolutionary stage; the shale minerals are mainly quartz and clay; and the pores are mainly intergranular, intragranular dissolved pores, organic matter pores and micro fractures. In addition, the average specific surface area (BET) of the shale is 5.171 m2/g; micropores account for 4.46% of the total volume; the specific surface area reaches 14.6%; and mesopores and macropores are the main pore spaces. There is a positive correlation between TOC and the quartz content of Wufeng-Longmaxi shale, and porosity is positively correlated with the clay mineral content. It is known that organic pores and the specific area develop more favorably when the clay mineral content is higher because the adsorption capacity is enhanced. In addition, as shale with a high clay mineral content and high TOC content promotes the formation of a large number of nanopores, it has a strong adsorption capacity. Therefore, the most favorable interval for shale gas exploration and development in this well is the shale that has a high TOC content, high clay mineral content, and a suitable quartz content. The findings of this study can help to better identify shale reservoirs and predict the sweet point in shale gas exploration and development. [ABSTRACT FROM AUTHOR]

Tumor suppressor gene PTEN is frequently mutated in a wide variety of cancers. However, the downstream targets or signal transduction pathways of PTEN remain not fully understood. By analyzing Pten -null mouse embryonic fibroblasts (MEFs) cell lines and their isogenic counterparts, we showed that loss of PTEN led to increased cyclooxygenase2 (COX2) expression in an AKT-independent manner. Moreover, we demonstrated that PTEN deficiency promotes the transcription of COX2 via upregulation of the transcription factor Krüppel-like factor 5 (KLF5). Knocked down the expression of COX2 suppressed proliferation, migration and tumoral growth of Pten -null cells. Further experiments revealed that COX2 enhanced Pten -null MEFs growth and migration through upregulation of NADPH oxidase 4 (NOX4). In addition, MK-2206, a specific inhibitor of AKT, in combination with celecoxib, a COX2 inhibitor, strongly inhibited Pten -deficient cell growth. We concluded that KLF5/COX2/NOX4 signaling pathway is critical for cell growth and migration caused by the loss of PTEN, and the combination of MK-2206 and celecoxib may be an effective new approach to treating PTEN deficiency related tumors. • Loss of PTEN upregulates COX2 in an AKT-independent manner. • PTEN deficiency promotes the expression of COX2 through upregulation of KLF5. • Depletion of COX2 suppresses PTEN deficiency-induced tumorigenesis. • COX2 increases the proliferative and migratory capacities of Pten -null cells via elevation of NOX4 expression. • Celecoxib in combination with MK-2206 plays a stronger inhibitory role on the growth of Pten -/- cells than either drug alone. [ABSTRACT FROM AUTHOR]