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Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer stem cells (CSCs) properties, fuels tumor initiation, and contributes to tumor aggressiveness. Our previous study has demonstrated the oncogenic role of SOX2 in colorectal cancer (CRC). In this study, we sought to elucidate the underlying mechanisms. Cell function experiments were performed to detect chemoresistance, proliferation, stemness, migration, and invasion in vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, and immunofluorescence were performed to explore the regulation of ABCC2, β-catenin, and Beclin1 by SOX2. The carcinogenic role of SOX2-β-catenin/Beclin1-ABCC2 axis in vivo was analyzed by CRC tissues and xenograft models. Here, we reported that SOX2 sustained chemoresistance by transcriptional activation of ABCC2 expression. Suppressing either β-catenin or autophagy signaling curbed SOX2-driven chemoresistance, stemness, and epithelial–mesenchymal transition (EMT). Mechanistically, SOX2 combined with β-catenin and increased its nuclear expression and transcriptional activity. Transcriptional activation of Beclin1 expression by SOX2 consequently activating autophagy and inducing malignant phenotype. Furthermore, overexpression of β-catenin or Beclin1 facilitated ABCC2 expression. The clinical analyses showed that high expression of ABCC2 and Beclin1 were positively correlated with SOX2 and were associated with poor prognosis in CRC patients. Finally, xenograft models revealed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo. Conclusively, we demonstrated a novel mechanism by which the SOX2-β-catenin/Beclin1/autophagy signaling axis regulates chemoresistance, stemness, and EMT in CRC. Our findings provide novel insights into CRC carcinogenesis and may help develop potential therapeutic candidates for CRC.

Growing evidence indicates that a small number of cancer cells express stem cell markers and possess stem cell-like properties that promote malignant progression. Sex-determining region Y-box2 (SOX2) is a stem cell transcription factor essential for maintaining the properties of cancer stem cell (CSC). As CSC properties have been associated with angiogenesis and vasculogenic mimicry (VM), we aimed to comprehensively investigate whether SOX2 regulates CSC properties, angiogenesis, and VM in colorectal carcinoma (CRC) and its potential mechanism in this study. For this study, sphere formation assay, flow cytometry, cell survival analysis, tube formation, 3D culture, immunoblot, mouse model, and luciferase reporter assay were performed in vivo and in vitro. Expressions of SOX2 and miR-450a-5p in CRC tissue samples were examined through immunohistochemistry. First, the expression of SOX2 was not only associated with poor differentiation and prognosis but also promoted angiogenesis and VM. Knockdown of SOX2 ceased stemness properties, angiogenesis, and VM, along with decreased expression of CD133, CD31, and VE-cadherin as observed in functional experiments. Downregulation of SOX2 was found to inhibit tumorigenesis in vivo. Second, miR-450a-5p suppressed the expression of SOX2 by targeting its 3’UTR region directly and hence restrained SOX2-induced CSC properties, angiogenesis, and VM. Moreover, SOX2 overexpression preserved the miR-450a-5p-induced inhibition of CRC properties, angiogenesis, and VM. Finally, clinical samples exhibited a negative correlation between miR-450a-5p and SOX2. Patients with higher SOX2 and lower miR-450a-5p expressions had a poorer prognosis than patients with inverse expressions. Conclusively, we elucidated a unique mechanism of miR-450a-5p-SOX2 axis in the regulation of stemness, angiogenesis, and VM, which may act as a potential therapeutic practice in CRC.

Vasculogenic mimicry (VM), a new model of angiogenesis, fulfills the metabolic demands of solid tumors and contributes to tumor aggressiveness. Our previous study demonstrated the effect of SOX2 in promoting VM in colorectal cancer (CRC). However, the underlying mechanisms behind this effect remain elusive. Here, we show that SOX2 overexpression enhanced glycolysis and sustained VM formation via the transcriptional activation of lncRNA AC005392.2. Suppression of either glycolysis or AC005392.2 expression curbed SOX2-driven VM formation in vivo and in vitro. Mechanistically, SOX2 combined with the promoter of AC005392.2, which decreased H3K27me3 enrichment and thus increased its transcriptional activity. Overexpression of AC005392.2 increased the stability of GLUT1 protein by enhancing its SUMOylation, leading to a decrease in the ubiquitination and degradation of GLUT1. Accumulation of GLUT1 contributed to SOX2-mediated glycolysis and VM. Additionally, clinical analyses showed that increased levels of AC005392.2, GLUT1, and EPHA2 expression were positively correlated with SOX2 and were also associated with poor prognoses in patients with CRC. Our study conclusively demonstrates that the SOX2-lncRNA AC005392.2-GLUT1 signaling axis regulates VM formation in CRC, offering a foundation for the development of new antiangiogenic drugs or new drug combination regimens.

Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC. The molecular mechanisms underlying metabolic remodelling in colorectal cancer (CRC) are not completely elucidated. Here, they authors show that the oncogenic protein MYG1 promotes CRC progression not only through regulating mitochondrial activity, but also through activating a nuclear-associated pathway for glycolysis increase.

Resource utilization of construction and demolition waste (CDW) is regarded to be an important means of achieving the sustainable development of the economy and the environment. However, previous research has not fully considered the green degree of products in the demand function of CDW remanufactured products. This study aimed to clarify how consumers’ green preferences and government subsidies affect decision making in the supply chain. First, a CDW resource utilization supply chain model composed of building materials manufacturers and retailers was constructed using consumer behavior theory. Second, the optimal decision making of members under conditions of decentralized and centralized decision making was analyzed using the Stackelberg game solution. Finally, the validity of the model and conclusions were verified by numerical simulation. The main conclusions are as follows. Government subsidies have a different impact on the pricing of new building materials products and CDW remanufactured products. Under decentralized decision making, the optimal profit of the CDW resource utilization supply chain with government subsidies is higher. However, under centralized decision making, the optimal profit is also related to consumers’ green preferences. According to consumers’ green preferences, choosing different decision-making models can not only improve the total profit of the CDW resource utilization supply chain, but also improve the reuse rate of CDW.

Using surfactants to extract oil, the anionic surfactant Karamay petroleum sulfonate (KPS), the zwitterionic surfactant octadecyl betaine (BS-18) and the nonionic surfactant coconut oil fatty acid diethanolamide (6501) were selected for adsorption experiments with minerals contained in the conglomerate reservoir with different mineral compositions to study the adsorption law of different types of surfactants. Zeolite and montmorillonite, which have the highest specific surface area and zeta potential among the minerals in the conglomerate reservoir, have the most obvious adsorption effect on surfactants, resulting in a large amount of adsorption of KPS and BS-18. The three types of surfactants were then used to conduct physical simulation oil recovery experiments with conglomerate core samples, and the results showed that 6501 had better overall performance, the best adsorption resistance, and a higher degree of recovery in oil recovery experiments, which provided a basis for the selection of surfactants in the process of chemical drive in conglomerate reservoirs. Article Highlights The complex mineral composition and physicochemical properties of conglomerate reservoirs in the Junggar Basin are analyzed. The adsorption degree of different types of surfactants on rock minerals in conglomerate reservoirs was studied. The formula for chemical oil recovery in conglomerate reservoirs can be optimized through analysis and research.

Purpose: Statins are commonly prescribed medications that potently reduce cholesterol levels and the risk of cardiovascular events. Preclinical studies suggested statins also possess cancer chemopreventive properties. However, the clinical studies provided contradictory results as to whether statins influence the risk of pancreatic cancer. Herein, we present this meta-analysis to assess the association between statin use and risk of pancreatic cancer. Methods: We conducted a comprehensive search up to August 2011 for the eligible studies. Pooled relative risk (RR) estimates and corresponding 95 % confidence intervals (CIs) were calculated using the inverse-varianceweighted random-effects model. Subgroup analyses were conducted where data were available. Heterogeneity was assessed by the Cochran's Q test and the I² statistic. Results: We included 16 studies that involving 1,692,863 participants and 7,807 pancreatic cancer cases. Pooled results only indicated a non-significant decrease of pancreatic cancer risk among all statin users (RR 0.89; 95 % CIs, 0.74-1.07). Similar results were obtained in the subgroup analyses of the long-term (more than 4 years) follow-up (RR 0.94, 0.81-1.08) and statin use (RR 0.97, 0.76-1.23), and a null association was found between lipophilic statin use and pancreatic cancer risk (RR 1.03, 0.92-1.16). No evidence of publication bias was observed in the present meta-analysis. However, significant heterogeneity was detected among all studies (p < 0.00001, I² = 81 %). Conclusions: In conclusion, our results suggest that there is no association between statin use and pancreatic cancer risk, when statins are taken at daily doses for cardiovascular event prevention.

Colorectal cancer (CRC) poses a significant global health challenge, yet immune checkpoint blockade (ICB) therapy benefits only a small subset of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumours. Through analyses of public single-cell and spatial transcriptomic datasets, primary mouse cell sorting and adoptive transfer experiments, flow cytometry, multiplex immunofluorescence, immunohistochemistry, and coimmunoprecipitation, we revealed that sentrin-specific protease 7 (SENP7) promotes regulatory B-cell (Breg) differentiation and inhibits senescence by activating the expression of the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) via deSUMOylation, thereby enhancing the expression of genes such as interleukin-10 (IL-10). Notably, targeting SENP7 in B cells improved the antitumour efficacy of anti-PD-1 therapy. These findings suggest that inhibiting SENP7 may offer a promising strategy to sensitize immunologically \"cold\" tumours to immune checkpoint blockade.

In recent years, the generation of a large amount of construction and demolition waste (CDW) has threatened the public environment and human health. The inefficient supply chain of CDW resource utilization hinders the green development of countries around the world, including China. This study aims to reveal the impact of information sharing regarding recyclers’ market demand forecast on the performance of CDW resource utilization supply chains. Therefore, this paper uses the incomplete information dynamic game method to establish and solve the decision-making model of the construction and demolition waste resource utilization supply chain under the conditions of recyclers sharing and not sharing their information. The paper then obtains the Bayesian equilibrium solution and the optimal expected profit for each party. Finally, a numerical simulation was used in order to verify the validity of the model and conclusions. The main conclusions are as follows. In the CDW resource utilization supply chain, if the recycler is more pessimistic about the market’s demand forecast, their information sharing makes the remanufacturer more motivated to improve their level of environmental responsibility. In addition, information sharing by recyclers is always beneficial in increasing the profit of the remanufacturer, but it also may make the recycler lose profit. When the efficiency of the environmental responsibility investment of remanufacturers is in a high range, information sharing increases the profits of recyclers. Conversely, information sharing has no significant effect on the profits of recyclers. The impact on the profits of the entire CDW resource utilization supply chain depends on the intensity of competition among channels, the market share of offline recycling channels and the efficiency of environmental responsibility investments.

The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to measure 21 cm emission from the primordial intergalactic medium (IGM) throughout cosmic reionization (z = 6-12), and to explore earlier epochs of our Cosmic Dawn (z ∼ 30). During these epochs, early stars and black holes heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is designed to characterize the evolution of the 21 cm power spectrum to constrain the timing and morphology of reionization, the properties of the first galaxies, the evolution of large-scale structure, and the early sources of heating. The full HERA instrument will be a 350-element interferometer in South Africa consisting of 14 m parabolic dishes observing from 50 to 250 MHz. Currently, 19 dishes have been deployed on site and the next 18 are under construction. HERA has been designated as an SKA Precursor instrument. In this paper, we summarize HERA's scientific context and provide forecasts for its key science results. After reviewing the current state of the art in foreground mitigation, we use the delay-spectrum technique to motivate high-level performance requirements for the HERA instrument. Next, we present the HERA instrument design, along with the subsystem specifications that ensure that HERA meets its performance requirements. Finally, we summarize the schedule and status of the project. We conclude by suggesting that, given the realities of foreground contamination, current-generation 21 cm instruments are approaching their sensitivity limits. HERA is designed to bring both the sensitivity and the precision to deliver its primary science on the basis of proven foreground filtering techniques, while developing new subtraction techniques to unlock new capabilities. The result will be a major step toward realizing the widely recognized scientific potential of 21 cm cosmology.