Due to its regulation of CDK1/2 phosphorylation, WEE1 plays essentially roles in the regulations of G2/M checkpoint and DNA damage response (DDR). WEE1 inhibition can increase genomic instability by inducing replication stress and G2/M checkpoint inactivation, which result in increased cellular sensitivity to DNA damaging agents. We considered an increase in genomic instability induced by WEE1 inhibition might be used to augment the effects of drugs targeting DNA repair protein. Typically, PARP inhibitors are effective in germline BRCA 1/2 mutated breast and ovarian cancer, but their applicabilities in triple-negative breast cancer (TNBC) are limited. This study was conducted to investigate the antitumor effects of the WEE1 inhibitor, AZD1775, and the mechanism responsible for its potentiation of sensitivity to olaparib (a PARP inhibitor) via the modulation of DDR in TNBC cells. Our results suggest that AZD1775 could be used to broaden the application range of olaparib in TNBC and provide a rationale for a clinical trial of combined olaparib and AZD1775 therapy. Triple-negative breast cancer (TNBC) is a breast cancer subtype that lacks estrogen receptor (ER) and progesterone receptor (PR) expression and does not exhibit human epidermal growth factor receptor 2 (HER2) amplification. TNBC accounts for 15-20% of all breast cancer cases and has more aggressive characteristics and higher rates of distant recurrence and shorter overall survivals than other breast cancer subtypes 1. TNBC is also a heterogeneous disease with various subtypes, and as a result, translational studies based on the use of agents that target specific subtypes are being actively pursued 2. However, the clinical applications of such agents are currently very limited, and thus, the systemic treatment of TNBCs is largely dependent on platinum containing, taxane, and anthracycline based chemotherapies. Unfortunately, durable responses to these treatments are limited by high resistance and recurrence rates and by adverse toxic effects. As a result, many research programs are being conducted to identify new targeting therapies effective in TNBC. As reported in the cancer genome atlas (TCGA) database, alterations of RB and CCND1 are present in 22% of TNBC cases, and TP53 mutations are detected in more than 80% 3. Thus, dysregulation of the G1 cell cycle checkpoint is common in TNBC, and this results in higher mutation burdens because of high proliferation rates and replication stress accumulation observed at higher Ki-67 levels, which in turn, cause genomic instability 4. Specifically, cell cycle checkpoint defects promote DNA replication and cell division, which result in damaged DNA accumulation and increase genetic instability 5. These features have been proposed under the concept of synthetic lethality to inhibit other cell cycle checkpoints that were normally maintained, leading to cell death due to increased genetic instability caused by abnormal cell cycle progression.
We have demonstrated electrically and optically enhanced MoS2 phototransistors on a flexible polyarylate substrate using poly(4-vinylphenol) (PVP) as a gate dielectric as well as an encapsulation layer. With the PVP encapsulation, the field-effect mobility (μFE) increases up to twofold, and the subthreshold slope as well as the on/off ratio (ION/IOFF) improves, which are desirable features for the photoresponsive characteristics. Consequently, both photoresponsivity and detectivity increase up to two orders of magnitude (×100) from visible to infrared spectrum. Such enhancement is associated with the n-doping effect of hydroxyl groups in PVP and reduced recombination centers by filling interface traps and surface states. Our results reveal that the transparent PVP polymer can be a promising encapsulation method in order to enhance the electrical and photoresponsive characteristics of MoS2-based flexible devices.
Among various energy harvester paradigms, the simple cantilever-structured magneto–mechano–electric (MME) energy generator comprises a piezoelectric material laminated on a magnetostrictive metal plate and permanent magnets as proof mass, exhibiting excellent magnetic energy-harvesting performance. The current challenge in using MME energy harvesters is the mechano–electric coupling at the interface between the piezoelectric material and magnetostrictive metal layer, which depends significantly on the mechanical properties of the interfacial adhesive layer. In this study, the effects of four types of adhesive interfacial layers on the output power and environmental and fatigue resistances of MME harvesters are systematically investigated. An optimized MME energy generator with an adhesive interfacial layer of 18.8 μm thickness and elastic modulus of 3.1 GPa achieves colossal enhancement (∼300%) with a maximum output power density of 0.92 mW/cm2, while a 10 Oe (=10 G = 1 mT in air; 60 Hz) magnetic field is applied. In addition, the generator exhibits a robust endurance of continuous 108 fatigue cycles and excellent temperature stability in the range of −30 to 70 °C. The presented MME generator, which harvests stray magnetic energy reliably, is promising as a low-cost and efficient autonomous power source for Internet of Things devices, wireless sensor networks, and so on.
Medical supply chain communication networks engender critical information and data. Notably in the COVID era, inner personal and private information is being shared between healthcare providers regarding the medical supply chain. In recent years, multiple cyber-attacks have targeted medical supply chain communication networks due to their lack of security measures. In the era where cyber-attacks are cheaper and easier due to the computational power and various algorithms available for malicious uses, security, and data privacy requires intensive and higher measures. On the other hand, Information Hiding Techniques (IHT) compromise various advanced methods to hide sensitive information from being disclosed to malicious nodes. Moreover, with the support of Blockchain, IHT can bring higher security and the required privacy levels. In this paper, we propose the implementation of Blockchain and smart contract with the information hiding technique to enhance the security and privacy of data communication in critical systems, such as smart healthcare supply chain communication networks. Results show the feasibility of the framework using Hyperledger smart contract along with the desired security level.
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