Developing novel approaches to reverse the drug resistance of tumor-repopulating cells （TRCs） or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we ...show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparficles （T-MPs） containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tu- mor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.
Digital Twin technology has been widely applied in various industry domains. Modern industrial systems are highly complex consisting of multiple interrelated systems, subsystems and components. ...During the lifecycle of an industrial system, multiple digital twin models might be created related to different domains and lifecycle phases. The integration of these relevant models is crucial for creating higher-level intelligent systems. The Cognitive Digital Twin (CDT) concept has been proposed to address this challenge by empowering digital twins with augmented semantic capabilities. It aims at identifying the dynamics and interrelationships of virtual models, thus to enhance complexity management capability and to support decision-making during the entire system lifecycle. This paper aims to explore the CDT concept and its core elements following a systems engineering approach. A conceptual architecture is designed according to the ISO 42010 standard to support CDT development; and an application framework enabled by knowledge graph is provided to guide the CDT applications. In addition, an enabling tool-chain is proposed corresponding to the framework to facilitate the implementation of CDT. Finally, a case study is conducted, based on simulation experiments as a proof-of-concept.
Moraine dam breaches occur suddenly and have severe consequences. However, breach-process prediction is challenging. Breach-notch excavation is crucial for risk reduction, but no consensus have been ...reached regarding the optimal notch shape. This study considers the typical characteristic parameters of the Jialongcuo glacial lake and trapezoidal, triangular, and compound notches. In this study, three flume tests were conducted to study the breach-shape impact on the peak discharge and erosion development of the dam during dam-breaching process, while controlling the excavation volume and depth. The compound- and triangular-breach peak discharge values surpass that of the trapezoidal type by 18.4% and 12.2%, respectively. Additionally, the trapezoidal breach exhibits average erosion rates that are > 50% lower, both laterally and vertically, at its initial erosion section, indicating milder erosion and improved outflow efficiency. The results emphasize that the notch-bottom width is critical, and that a trapezoidal notch with equal depths yields higher initial outflow efficiency owing to its greater bottom width. An analysis based on dam erosion process theory agrees with the experimental results and confirms the conclusions. Based on the erosion rates taken from the experiments, a comparison of sediment transport values is given for the three tests. The results indicate that the trapezoidal notch has a relatively small bed load transport. Our work is expected to provide references for the selection of better notch shape.
Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces ...tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program. Blocking the IDO/AhR metabolic circuitry not only abrogates IFN-γ-induced dormancy but also results in enhanced repression of tumour growth by IFN-γ-induced apoptosis of TRCs both in vitro and in vivo. These data present a previously unrecognized mechanism of inducing TRC dormancy by IFN-γ, suggesting a potential effective cancer immunotherapeutic modality through the combination of IFN-γ and IDO/AhR inhibitors.
Supply Chain Finance (SCF) refers to the financial service in which banks rely on core enterprises to manage the capital flow and logistics of upstream and downstream enterprises. SCF adopts a ...self-testing and closed-loop credit model to control funds and risks. The key factor in a successful SCF service is the deployment of SCF business-oriented information systems that allow businesses to form partnerships efficiently and expedite cash flows throughout the supply chain. Blockchain Technology (BCT), featuring decentralization, tamper-proofing, traceability, which is usually paired with the Internet of Things (IoT) in real-world contexts, has been widely adopted in the field of finance and is perfectly positioned to facilitate innovative collaborations among participants in supply chain networks. In this paper, we propose a BCT and IoT-based information management framework (named BC4Regu), which works as the regulatory to improve the information transparency in the business process of SCF. With BC4Regu, the operation cost of the whole supply chain can be significantly reduced through the coordination and integration of capital flow, information flow, logistics and trade flow in the supply chain. The contributions in this paper include: (1) proposing a novel information management framework which leverages Blockchain and IoT to solve the problem of information asymmetry in the trade of SCF; (2) proposing the technical design of BC4Regu, including the Blockchain infrastructure, distributed ledger-based integrated data flow service, and reshaped SCF process; and (3) applying BC4Regu to a group of scenarios and conducting theoretical analysis by introducing the principal-agent model to validate the BC4Regu.
ABSTRACT
I develop a theory to study the consequences of providing more detailed information to rationally inattentive investors. I first consider a simple data‐provision problem and show that adding ...more data or detail in financial statements can make it more difficult for investors to extract information. Consequently, investors who have limited information‐processing capacity may prefer less detailed information. I also show that when investors' decisions are complements, providing details in addition to a summary may reduce investors' welfare. More specifically, because of increased disclosure of details, a coordination failure could occur in investors' attention‐allocation decisions. By showing that adding more detail in financial statements can lead to an information overload problem for investors, this study yields valuable insights for accounting standard setters.
Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in ...diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.
Development of a sustainable route for the synthesis of Fe-ZSM-5 zeolites is important due to their diverse applications in different fields. Herein, we report a novel, efficient and an eco-friendly ...dry gel conversion method to one-pot synthesize Fe-ZSM-5 zeolite containing framework heteroatoms under the conditions that neither the template nor the seed crystal was added. The present strategy not only improves the synthesis efficiency of zeolites, but also reduces the cost and environmental pollution by avoiding using ordinary template. The physicochemical properties of the synthesized samples were analyzed by XRD, N
2
adsorption–desorption, SEM, UV–visible diffuse reflectance, XPS, FT-IR and NH
3
-TPD techniques. The characterization results revealed that the Fe species in the one-pot synthesized Fe-ZSM-5 zeolite (Fe-ZSM-5-In) mainly exist in the zeolite framework in the form of Fe
3+
, while those in the Fe/ZSM-5 zeolite prepared by impregnation (Fe/ZSM-5-Im) mostly exist on the surface of the zeolite in the form of non-framework Fe such as oligomeric Fe
x
3+
O
y
clusters and Fe
2
O
3
particles. Fe-ZSM-5-In possessed enhanced acid amount and better distribution of framework Fe
3+
species than Fe/ZSM-5-Im. The results of catalytic performance evaluation show that the propylene yield is improved by the Fe modified ZSM-5 additives due to enhanced acid content and acid strength. Compared with the Fe/ZSM-5-Im additive, the Fe-ZSM-5-In additive has higher propylene yield and lower coke yield owing to its more acid content and lower dehydrogenation activity.
Graphical Abstract
The Fe-ZSM-5 zeolite containing the framework heteroatoms was one-pot synthesized by the dry gel conversion (DGC) method under the conditions that neither the template nor the seed crystal is added, which exhibits improv ed catalytic activity and has higher propylene yield than the Fe/ZSM-5 additive in the catalytic cracking process.
Ovarian cancer (OC), known for its lethality and resistance to chemotherapy, is closely associated with iron metabolism and ferroptosis—an iron-dependent cell death process, distinct from both ...autophagy and apoptosis. Emerging evidence suggests that dysregulation of iron metabolism could play a crucial role in OC by inducing an imbalance in the redox system, which leads to ferroptosis, offering a novel therapeutic approach. This review examines how disruptions in iron metabolism, which affect redox balance, impact OC progression, focusing on its essential cellular functions and potential as a therapeutic target. It highlights the molecular interplay, including the role of non-coding RNAs (ncRNAs), between iron metabolism and ferroptosis, and explores their interactions with key immune cells such as macrophages and T cells, as well as inflammation within the tumor microenvironment. The review also discusses how glycolysis-related iron metabolism influences ferroptosis via reactive oxygen species. Targeting these pathways, especially through agents that modulate iron metabolism and ferroptosis, presents promising therapeutic prospects. The review emphasizes the need for deeper insights into iron metabolism and ferroptosis within the redox-regulated system to enhance OC therapy and advocates for continued research into these mechanisms as potential strategies to combat OC.
Abstract The complex characteristics of full-bridge LLC converters and PFM mode of operation result in a variety of operating modes and characteristic changes at different operating frequencies, thus ...increasing the difficulties in small signal characteristic analysis and good compensator design. In terms of control strategy, the traditional linear controller has limited response performance under various operating conditions such as input voltage ripple perturbation, input voltage mutation, and load mutation. To obtain greater transient response performance, stronger disturbance capability, and higher input stability of the system under different operating conditions, this paper proposes a new integral global sliding mode control law for LLC converters. In contrast to conventional control methods, the proposed control strategy exhibits enhanced dynamic response capabilities in the presence of load variations. It effectively mitigates jitter issues during steady-state operation, demonstrating a superior control performance.
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