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The common risk of high-pressure hydrogen leakage seriously affects the safety of hydrogen refueling stations (HRS). In this study, we have developed a hybrid model (WD-KNN-CNN) based on wavelet denoising (WD) and deep learning to predict the hydrogen leakage location and intensity in HRS. The raw data were calculated using validated Computational Fluid Dynamics (CFD), and the WD-processed raw data were utilized as input data for the hybrid model. The K-nearest Neighbors (KNN) is employed to identify the leak location, while a two-dimensional Convolutional Neural Network (CNN) is utilized to extract temporal and spatial distribution features from the concentration sequence for intensity prediction. Bayesian optimization is applied to determine the optimal hyperparameter combination for the model. The results demonstrate that the model achieves a prediction accuracy of 99.14% for leak location and 97.42% for intensity level. Furthermore, through the reduction of sensor quantity, we tested the model's performance and found that utilizing 14 sensors as input resulted in 91.3% accuracy for leak location and 90.8% for intensity level prediction. This hybrid model provides a method for safety monitoring in HRS and offers guidance for personnel response during leak incidents. [Display omitted] • Hybrid model for Predicting Leakage Location and Intensity in HRS. • Training hybrid model using results from numerical simulation. • Conducting reduced-scale experiments to validate numerical simulation accuracy. • Compared the effect of sensor arrangement on the WD-KNN-CNN prediction accuracy. [ABSTRACT FROM AUTHOR]

In this study, the deformation behavior of body-centered-cubic (BCC) VNbTa medium-entropy alloy (MEA) was studied under different strain rates ranging from 10−3 s−1 to 5000 s−1 using screw-driven testing machine and split Hopkinson pressure bar (SHPB), respectively. The alloy presents an outstanding synergy of strength and plasticity without any adiabatic shear bands even at a strain rate of 5000 s−1. Moreover, the yield strength of the alloy displays an obvious strain rate dependence, increasing by ∼94.4% from 842 MPa at 10−3 s−1 to 1637 MPa at 5000 s−1. The strain rate sensitivity (SRS) factor m and highest temperature rise under dynamic loading is calculated to be 0.2991 and 182 K, respectively, which means a strong strain rate hardening and thermal softening resistance. Microstructure evolution analyses demonstrate a transition of deformation mechanism from single dislocation slip controlling in low strain rate to a synergy of mechanical twinning and dislocation slip in high strain rate. Therefore, the excellent dynamic mechanical properties could be attributed to the synergistic effects of the strong strain rate hardening and thermal softening resistance, the mechanical twins, and the cell structures and microbands derived from dislocation slip controlling. In addition, the dynamic deformation behavior of VNbTa could also be described by a classical Johnson-Cook model. Combining the excellent cryogenic temperature mechanical properties (tensile strength of ∼1930 MPa and fracture elongation ∼27%), the present work further indicates that the VNbTa MEA has great potential for engineering applications under some extreme circumstances. • Dynamic compression tests of the VNbTa MEA are conducted using split Hopkinson pressure bar. • Alloy exhibits excellent dynamic mechanical properties and obvious strain rate dependence of yield strength. • Strong thermal softening resistance suppresses adiabatic shear during dynamic loading. • Synergy of mechanical twinning and dislocation slip dominates the dynamic deformation of alloy. • Dynamic deformation behavior of alloy can be described by a modified Johnson-Cook model. [ABSTRACT FROM AUTHOR]

To explore the learning experiences and career development expectations of nursing master's degree students. With increasing demands for improved quality of life, there is a growing need for nursing graduate programs in clinical care. However, the existing training programs for nursing master's students in China require improvement. It is essential to analyze students' learning experiences, perceptions of the current status of nursing and expectations of the nursing profession to enhance and develop university training programs. A descriptive qualitative study employing semi-structured interviews. Semi-structured interviews were conducted with 14 nursing master's degree students. The data obtained were analyzed using Colaizzi's seven-step phenomenological analysis method. The study adhered to the consolidated criteria for reporting qualitative research (COREQ). Three main themes emerged from the analysis—Theme 1: Career expectations, encompassing motivations for pursuing the nursing master's program and career aspirations; Theme 2: Study experiences, including nursing professional ability, nursing management ability, self-awareness ability and moral literacy; Theme 3: Occupational dilemmas, encompassing the current challenges and coping strategies. The learning experiences of nursing master's students in universities are closely linked to their training programs. A disparity exists between students' career expectations and the actual employment landscape for nursing master's degree students. [ABSTRACT FROM AUTHOR]

In this study, the deformation behavior of an equiatomic VNbTa medium-entropy alloy with a BCC single phase is studied by tensile tests at cryogenic temperatures. The results show that the alloy presents a strong strain hardening capability, which leads to a high ultimate tensile strength of 1930 MPa while maintaining a high fracture elongation of ∼27%, without a ductile to brittle transition. The excellent cryogenic temperature mechanical properties of the present alloy are attributed to the cooperative of {112}〈111〉 deformation twins, dislocation interaction, and entanglement caused by the continuing cross-slip of dislocation. The localized severe lattice distortions caused by the large atomic size misfit of elements among Nb, Ta and V play a major role in the cross-slip of dislocation. • Tensile tests of BCC VNbTa MEA were conducted at cryogenic temperature. • The alloy exhibited an ultra-high yield strength and excellent strain hardening ability. • The excellent mechanical properties ascribed to synergistic of mechanical twins, dislocation interaction and entanglement. • The local severe lattice distortion plays a critical role during deformation of alloy. [ABSTRACT FROM AUTHOR]

Plant subclass III SnRK2 protein kinases are widely recognized as key regulators of abscisic acid signaling and downstream stress responses. Recent research has revealed that SnRK2s function in growth-promoting signaling pathways, suggesting that SnRK2s tightly control the yin–yang relationship between plant growth and stress responses. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BS) is an autosomal dominant disease. The most common causes of BS are loss-of-function mutations occur in the SCN5A gene which encodes the sodium channel protein Nav1.5. BS has a higher incidence rate in males and the underlying mechanisms of the gender inequality are not yet fully understood. Considering sex hormones are among the most important factors behind gender differences and have previously been shown to regulate the activity of multiple cardiac ion channels, we hypothesized that sex hormones also affect Nav1.5 function which lead to BS predominantly affecting males. In this study, we investigate the protein expression level and current of Nav1.5 in the HEK293 cells cotransfected with SCN5A and sex hormone receptor plasmids using both wild-type SCN5A and BS-associated SCN5A channel mutants R878C and R104W. Our findings showed that sex hormones have no effects on the protein expression level and current of the wild-type Nav1.5, neither does it affect the protein expression level and current of BS-associated Nav1.5 mutants R878C and R104W, regardless of homozygous or heterozygous state. Our results suggest that the male preponderance of BS does not arise from the effects of the sex hormones on Nav1.5. Further studies are needed to explain the male preponderance of this disease. [ABSTRACT FROM AUTHOR]

Abstract Xinjiang is the major energy production area, and one of the regions with the most serious water resources scarcity issues in China. In particular, the coal-fired power and coal chemical industry base in East Junggar Basin has faced severe carbon emissions and water shortages. Based on the 3D heterogeneous geologic model of the East Junggar Basin, the research of field-scale CO 2 enhanced water recovery (CO 2 -EWR) was carried out to provide technical reference for the future field-scale CO 2 -EWR engineering practice in Xinjiang to solve the carbon emission and water shortage issues. The CO 2 -EWR technology can greatly relieve the reservoir pressure buildup, with a maximum cumulative CO 2 injection and storage of 100 Mt (3 times more than CO 2 Geological Storage only) and a maximum saline water production of 129.4 Mt (100 times more than saline water production only). [ABSTRACT FROM AUTHOR]

Abstract For electric vehicles (EVs), accurate State of Charge (SoC) estimation of battery contributes to ensure battery safety and improve driving mileage. Therefore, its research has essential application value. However, accurate SoC estimation of the battery relies on precise battery model parameters and capacity. This paper mainly carries out three aspects of work. (1) A battery equivalent circuit model is established, and the Forgetting Factor Recursive Least Squares (FFRLS) method is used to realize online identification of model parameters. (2) Based on the Arrhenius equation, the inverse power law equation and the battery capacity degradation equation, the battery capacity degradation model under dynamic stress is established to achieve the online prediction of battery capacity. (3) Based on equivalent circuit model, battery capacity degradation model and Adaptive Extended Kalman Filtering (AEKF) algorithm, an adaptive SoC estimation method is proposed. Simulation results show that the maximum estimation error of battery capacity and SoC is less than 2.5% and 1.5% respectively. [ABSTRACT FROM AUTHOR]

Abstract A traditional logic threshold control strategy (LTCS) is proposed but simulation results show control effects have a large gap with pseudo-spectral optimal results. To narrow this gap, the optimization is analyzed, the power relationship between the hybrid energy storage system (HESS) and the vehicle load is determined and the optimal power distribution between the battery and the ultra-capacitor is obtained. A near-optimal LTCS is presented using valuable control rules extracted by analyzing optimal control actions. The near-optimal LTCS can fully use high power characteristics of ultra-capacitor, avoid battery being damaged by high charge and discharge current, and make battery SOC consumption decreased by 2.0%. The hardware-in-the-loop (HIL) experiment is carried out and further validates that the near-optimal LTCS is real-time and reliable. [ABSTRACT FROM AUTHOR]

Hydrogen refueling stations (HRSs) play a vital role in the hydrogen energy industry and are being built worldwide. However, the potential risk of hydrogen leakage poses a significant challenge. Accurately predicting the consequences of such accidents is crucial for effective mitigation. Traditional methods, like numerical simulation, provide accurate results but lack timely predictions. To address this, we propose a hybrid surrogate model that combines Generative Adversarial Network (GAN) and Long Short-Term Memory Network (LSTM), incorporating Deep Neural Network (DNN) for predicting hydrogen leakage consequences in HRSs based on source parameters. The surrogate model was trained using training samples generated through numerical simulation. Reduced-scale experiments were conducted to verify the results of numerical simulations and assess the surrogate model's generalization ability. Results demonstrate the model's ability to predict hydrogen distribution after an accident, indicating its potential for real-time decision making in emergency response plans. • Hybrid GAN and LSTM surrogate model for accident consequence prediction in HRS. • Fused DNN enables consequence prediction based on leakage source parameters. • Training surrogate models using results from numerical simulation. • Generalizability of surrogate model was verified using reduced-scale experiments. [ABSTRACT FROM AUTHOR]

Aqueous hexavalent chromium (Cr(VI)) is an environmental safety problem that seriously threatens ecosystems and human health. Herein, SnS 2 nanosheet array catalysts on carbon cloth (CC) for microwave-induced catalytic reduction of Cr(VI) were prepared by a simple hydrothermal method. Benefiting from the unique interfacial and the improved electron transfer effect between the SnS 2 nanosheet arrays and the CC substrate, the reduction ratio of the CC@SnS 2 nanosheet array catalysts reached 100 % for a Cr(VI) solution (50 mg/L) under 35 min-microwave treatment at a frequency of 2.45 GHz and a power of 300 W. Density functional theory (DFT) calculations reveal that Cr 2 O 7 2− ions were more easily adsorbed on S atoms than HCrO 4 – ions in an acidic solution, indicating that the activity of S atoms was evidently superior to that of Sn atoms in CC@SnS 2 nanosheet arrays. This work provides an in-depth understanding of the mechanism of microwave-catalyzed removal of Cr(VI) and paves a new avenue for designing highly efficient microwave catalysts for wastewater treatment. [Display omitted] • SnS 2 nanosheet array catalysts grown on carbon cloth (CC@SnS 2) were prepared. • The Cr(VI) reduction efficiency of the CC@SnS 2 nanosheet array catalysts was 100 %. • DFT calculations were used to reveal the MW catalytic mechanism. • The superb electron conduction ability of CC@SnS 2 prompted rapidly transfer of e - . • S atoms were the optimal catalytic active sites of the CC@SnS 2 catalysts. [ABSTRACT FROM AUTHOR]

• Dissolution occurring in caprock after long-term water-rock interactions without CO 2 injection. • Self-sealing capability of caprock is enhanced under the condition of CO 2 injection with a maximum decrease of 40% in permeability. • Dolomite, siderite, magnesite and dawsonite are the key CO 2 trapping minerals for the enhancement of caprock sealing. • The dissolution of albite, chlorite and calcite provides the necessary Na+, Mg2+, Ca2+ and Fe2+ for the precipitation of carbonate minerals. This study investigates the influence of geochemical reactions among CO 2 , water and key minerals on caprock sealing using laboratory experiments and numerical simulations, based on mudstone caprock of the Triassic Heshanggou Formation at the Shenhua CCS demonstration project in Ordos Basin. The results show that there is an obvious dissolution occurring in caprock after long-term water-rock interactions without CO 2 injection, with a maximum increase of 11% in caprock permeability. The dissolution of kaolinite, chlorite, K-feldspar and quartz results in the increase of caprock permeability, and the precipitation of illite and hematite is the key factor effectively slowing down the change of permeability. However, the self-sealing capability of the caprock is continuously enhanced under the condition of CO 2 injection, with permeability reduced by 40% of the original permeability at maximum. The precipitation of carbonate minerals directly induces the change of caprock permeability, and the precipitation of Ca-smectite and quartz further promotes the caprock sealing. Dolomite, siderite, magnesite and dawsonite are the key CO 2 trapping minerals for the enhancement of caprock sealing, and the maximum amount of CO 2 trapped in mineral phase is 35.44 kg/m3 medium. The dissolution of albite, chlorite and calcite provides the necessary Na+, Mg2+, Ca2+ and Fe2+ for the precipitation of carbonate minerals, which is conducive to the enhancement of caprock sealing, while chlorite and calcite are the key minerals affecting the caprock sealing. The dissolution of K-feldspar is not conducive to the enhancement of caprock sealing. This study could provide a theoretical basis for selection of reservoir-caprock and safety evaluation of CO 2 geological storage. [Display omitted] [ABSTRACT FROM AUTHOR]

LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo . Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activated Wnt and TGFβ pathways, and its attenuation upregulated multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling. [ABSTRACT FROM AUTHOR]

In order to research the relationship between endophytic fungus and active ingredients in medicinal Paeonia suffruticosa , a total of 57 fungal isolates were isolated from the roots, stems, leaves and buds of medicinal plant Paeonia ostii ; mycelium was collected after these fungal isolates were fermented on PDA medium for a few days; then the mycelium products were extracted; their extracts were analyzed by gas chromatography–mass spectrometry. With this method, a strain endophytic fungi named J1-2 which can produce paeonol was screened. Paeonol produced by J1-2 was analyzed by using a high resolution mass spectrometer (HRMS) and nuclear magnetic resonance (NMR). The potential paeonol-procucing named J1-2 was identified Chaetomium based on morphological characteristics and ITS sequence analysis. The current research initially indicates that endophytic fungi can affect the potency of peony. At the same time it also indicates that the numerous endophytic fungi inside the medicinal Paeonia suffruticosa are precious resource for the pharmaceutical natural products that are originally from the Paeonia suffruticosa . [ABSTRACT FROM AUTHOR]

Unraveling the gene expression networks governing cancer initiation and development is essential while remains largely uncompleted. With the innovations in RNA-seq technologies and computational biology, long noncoding RNAs (lncRNAs) are being identified and characterized at a rapid pace. Recent findings reveal that lncRNAs are implicated in serial steps of cancer development. These lncRNAs interact with DNA, RNA, protein molecules and/or their combinations, acting as an essential regulator in chromatin organization, and transcriptional and post-transcriptional regulation. Their misexpression confers the cancer cell capacities for tumor initiation, growth, and metastasis. The review here will emphasize their aberrant expression and function in cancer, and the roles in cancer diagnosis and therapy will be also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Special current transformer (CT) is designed to induct power from the power transmission lines for an inspection robot. Equivalent circuit is used for calculating and modelling the parameters of the current transformer. Air gap analysis is given aiming at adapting dynamic range of bar current, and calculation of the effect of air gap is provided in detail. Ratio change of current transformer is introduced by which the secondary current could be adaptive to the bus current. Simulation results show that dynamic control of length of air gap and turns of the coils could make the current transformer be adaptive to the variable bus current and be more convenient for inducing power for the power transmission lines inspection robot. [Copyright &y& Elsevier]

Abstract: This paper analyses the cause of the major faults of the SF6 high voltage circuit breaker, and then introduces a solution using an embedded control system. The control system consists of the controller for every breaker and a supervisor control system in the control center. Then a double-annular fiber field-bus communication network for the control system is introduced, of which the data link layer is implemented by the CAN controller. According to the operation state of every node and the fiber, the fiber communication module of every node can be configured to several different transmission modes. Due to the influence of temperature, the empirical formula of Beattie-Bridgman is used to calculate the pressure of SF6. [Copyright &y& Elsevier]

Developing countries have begun to investigate bioreactor landfills for municipal solid waste management. This paper describes the impacts of leachate recirculation and recirculation loadings on waste stabilization, landfill gas (LFG) generation and leachate characteristics. Four simulated anaerobic columns, R1–R4, were each filled with about 30tons of waste and recirculated weekly with 1.6, 0.8 and 0.2m3 leachate and 0.1m3 tap water. The results indicated that the chemical oxygen demand (COD) half-time of leachate from R1 was about 180 days, which was 8–14 weeks shorter than that of R2–R4. A large amount of LFG was first produced in R1, and its generation rate was positively correlated to the COD or volatile fatty acid concentrations of influent leachates after the 30th week. By the 50th week of recirculation, the waste in R1 was more stabilized, with 931.2kg COD or 175.6kg total organic carbon released and with the highest landfill gas production. However, this contributed mainly to washout by leachate, which also resulted in the reduction of LFG generation potential and accumulation of ammonia and/or phosphorus in the early stage. Therefore, the regimes of leachate recirculation should be adjusted to the phases of waste stabilization to enhance efficiency of energy recovery. Integrated with the strategy of in situ leachate management, extra pre-treatment or post-treatment methods to remove the nutrients are recommended. [Copyright &y& Elsevier]

The industrial development of Xinjiang is facing serious carbon emissions and water shortage problems in this region. It is urgent to find a sustainable development way. CO 2 geological storage combined with enhanced water recovery (CO 2 -EWR) is a win-win technology that can increase CO 2 geological storage potential and obtain abundant groundwater resources meanwhile. A 3D heterogeneous geologic model was built to estimate the potential of field-scale CO 2 geological storage combined with enhanced water recovery according to the seismic, well logging data and well testing data of the Cretaceous Donggou Formation in the eastern Junggar Basin of China. Twelve injection-production scenarios were designed. The results show that CO 2 -EWR technology can greatly reduce the pressure buildup with the minimum pressure increase of 1.3 MPa and thus increase CO 2 injection with a maximum cumulative amount of 100 Mt, three times more than that for sole CO 2 injection. Also, it can enhance total production of deep saline water by a factor of ~100 compared to that for sole water production. Formation parameters such as permeability, porosity and slope of the reservoir primarily control the migration and dissolution of CO 2. The heterogeneity of the reservoir plays an important role in the CO 2 spatial distribution and even saline water production. One injection well with constant rate injection of CO 2 and one production well with constant pressure production of saline water scenario is the preferred option in engineering practice of eastern Junggar Basin, which can obtain the maximum amount of CO 2 injection and saline water resources. This study provides a technical reference for implementation of CO 2 -EWR at the field-scale or industrial-scale to solve CO 2 emission reduction and water shortage problems. [Display omitted] [ABSTRACT FROM AUTHOR]

Flake graphite (FG) poses challenges for incorporation into castables due to its hydrophobic nature. In this paper, a strategy combining liquid-phase shear exfoliation (LPSE) with hydrothermal processing was proposed to produce hydrophilic graphene nanosheet/AlOOH nanofiber (GN/ANF) composite powders to address this issue. Under optimal shear exfoliation conditions, the yield of graphene nanosheets (GNs) reached up to 57%. Following a straightforward hydrothermal treatment, the water contact angle of as-prepared GN/ANF composite powders decreased to 53.1°, compared to 103.6° of the original FG. Benefiting from the hydrophilic properties of the composite powders and the homogeneous dispersion of GNs in MgO castables, the sample containing 0.5 wt% GNs exhibited better high-temperature performance than its counterparts. Relative to the control specimen, the slag corrosion index of the sample containing 0.5 wt% GNs decreased from 0.60 to 0.13, while the thermal shock resistance increased by approximately 2.8 times. • Using the liquid-phase shear exfoliation method, the yield of graphene nanosheets reaches 57.02%. • After hydrothermal treatment, the water contact angle of graphene nanosheet/AlOOH nanofiber composite powders decreases from 103.6° to 53.1°. • Adding 0.5 wt% graphene nanosheets to MgO castables reduces the slag corrosion index from 0.60 to 0.13 and increases thermal shock resistance by about 2.8 times. [ABSTRACT FROM AUTHOR]

Liquid digestate containing high levels of nutrients and humic and fatty acids can affect vanadium species and their plant uptake. To elucidate the effects of liquid digestate on the valence state of vanadium in soil and plant tissue, as well as its effects on the microbial community and soil properties, we grew green bristlegrass (Setaria viridis), a native plant capable of growing in vanadium mining areas, in vanadium-contaminated soils sampled from a mining area and treated it with 5% and 10% liquid digestate for 90 d, respectively. Changes in the concentrations of pentavalent (V[V]) and tetravalent (V[IV]) vanadium in the soils and the shoots and roots of bristlegrass and the soil microbial abundance were measured. The results showed that vanadium existed mainly in the form of V(IV) in the soil but accumulated mainly in the form of V(V) in the bristlegrass. Liquid digestate markedly reduced V(V) concentrations in the soils (by up to 45%) and in the shoots and roots of green bristlegrass (by up to 98%). Liquid digestate enhanced the abundance of Bacteroidetes , which can reduce V(V) to lower valence state. Microbial reduction and phosphorus immobilization were responsible for downregulating V(V) concentrations in the plant and soil. The liquid digestate can be used to enhance in situ bioremediation of vanadium-contaminated soil in mining area. Image 1 • Liquid digestate could reduce V(V) concentrations in soil by up to 45%. • Liquid digestate could reduce V(V) concentrations in the shoots by up to 98%. • Bacteroidetes, Actinobacteria, and Firmicutes may responsible for V(V) reduction. • Vanadium mainly accumulated in the form of V(V) in the roots of Green bristlegrass. • Plant growth exerted little effect on valence state of vanadium in soil. [ABSTRACT FROM AUTHOR]

Abstract: Despite the initial efficacy of trastuzumab (commercially named Herceptin), acquired resistance in a majority of patients remains the biggest hurdle in breast cancer therapy. Recently, the Scripps Research Institute developed a method termed “instant immunity”, in which antibodies (chemical programmed antibody) are rapidly induced by chemicals like β-diketone. When β-diketone is chemically linked to peptides specifically targeting cancer cells, the instant chemical programmed antibody would clear the cancer cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC). This novel strategy has a super advantage over passive immunization or immunization with recombinant or vectored vaccines because it induces a universal immune response and memory. Theoretically, combination of the cancer cell specific recognition advantage of trastuzumab and cancerous cell clearance of active immunization would be an option for trastuzumab resistant patients, which harbors both the advantages of cancer specific targeting of trastuzumab and active immunization of the “instant immunity”, implicating a better clinical outcome. Further studies are needed to verify our hypothesis, which is worth validating. [Copyright &y& Elsevier]

Abstract: Cancer stem cells are regarded as the hurdle of cancer therapy at least partially due to their intrinsic resistance to therapy. To this end, chemotherapy is widely used for enrichment of cancer stem cells. In contrast to the dogma, we hypothesized that besides enrichment, cancer stem cells could also be induced by chemotherapy in those regions without sufficient drug delivery. Due to the imbalance of the angiogenesis and insufficient blood supply in certain regions of the tumor mass, chemotherapy delivery is compromised in these regions. The insufficient drug delivery in turn transforms the bulk cancer cells to stem cells rather than kill them through NFkappaB-HIF, NFkappaB-Wnt and other signals. Detection of the induction of cancer stem cells from the chemotherapy treated non-stem cancer cells would shed light on our hypothesis, which in turn would broad our understanding of clinical cancer chemotherapy. [Copyright &y& Elsevier]

Abstract: Colon cancer is one of the leading causes of cancer-related death worldwide. Genetic changes leading to aberrant activation of APC/β-catenin/TCF (canonical Wnt) pathway are considered as the initiating step in colon cancer. Abundant studies revealed that colon cancer is “Wnt addiction” and reduced the Wnt signal is of therapeutic value. Deregulation of the Rb/E2F1 pathway, as a result of alterations in members of the pathway, is a hallmark of many human cancers, but mutations in this pathway are rare in colon cancers. In contrast, suppression of E2F1 activity through mutation of the CDK8 pathway is common in colon cancer. Active E2F1 is found to repress the activity of β-catenin transcription and promote cell apoptosis. The mutually exclusive expression pattern and function between E2F1 and Wnt pathway suggest an antagonistic relationship between these two pathways in colon cancer evolution. We hypothesize that E2F1 functions as a barrier of aberrant Wnt signal, and that E2F1 repression is necessary for colon cancer development. This hypothesis suggests that reactivation of E2F1 might have therapeutic potential for most of the colon cancers, as most of the colon cancers have aberrantly activated Wnt signal. [Copyright &y& Elsevier]