In this paper, risk management strategies to minimize total damage due to COVID-19 are proposed. Total damage includes direct and indirect damage by infection and regulation respectively. The ...regulation of people's activities involves trade-offs between direct and indirect damage; thus, risk management should consider them. In implementing risk management strategies, the government must engage in risk communication to change people's behavior. Furthermore, the expansion of medical capacity is also necessary for risk management. The theoretical mechanisms of how medical capacity expansion reduces optimal total damage due to COVID-19 and the optimal level of regulation is described.
•A risk management strategy to minimize total damage due to COVID-19 is proposed.•Regulation of people's activities involves trade-offs between direct damage by infection and indirect damage by regulation.•Risk communication for behavioral change is indispensable in risk management.•Expanding medical capacity is necessary for risk management.
In many conventional plasma generation methods, a strong electric field is applied to a gas or liquid to generate plasma. In addition, metal oxides such as rare earth minerals and metals require ...enormous amounts of energy for their reduction reactions. In this paper, we propose a method of directly exciting the plasma from Mg and Ca metal solids, without gas or liquid, using a strong magnetic field and stabilizing it. Electrons and atoms are emitted by the induced current in a resonator operated in the TM110 mode; these electrons and atoms are generated as plasma in a magnetic field. The resonance frequency is then changed slightly from the TM110 mode to the TM111 mode while being limited to ∼40 MHz, ensuring that the microwave energy is supplied stably to the plasma and that light is emitted until the raw material is exhausted. The radicals and ions of the Mg and Ca metals possess sufficient Gibbs free energy for the reduction reactions and can therefore reduce scandium oxide and vanadium oxide at low temperatures. In the future, radicals with sufficient energy can be implemented in energy-saving processes in the field of materials processing.
The role of long noncoding RNAs (lncRNAs) in the epithelial‐mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular ...vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor‐β in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA‐133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV‐encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle‐transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA‐133b suppresses the EMT by targeting HULC. Extracellular vesicle‐encapsulated HULC could be a potential circulating biomarker for human PDAC.
Extracellular vesicle HULC can regulate cell invasion and migration through induction of epithelial‐mesenchymal transition. Extracellular vesicle HULC could compare favorably with CA19‐9 as a novel biomarker in liquid biopsy for human pancreatic ductal adenocarcinoma.
Approximately 12–15% of gastric cancers (GCs) are human epidermal growth factor receptor-2 (HER2)-positive (HER2 immunohistochemistry 3 + or 2 + /in situ hybridization +
ERBB2
/
CEP17
≥ 2.0). While ...the anti-HER2 monoclonal antibody trastuzumab, in combination with chemotherapy, is the standard treatment for HER2-positive GC, other HER2-targeted therapies have not demonstrated survival benefits in patients with GC, despite showing efficacy in patients with HER2-positive breast cancer. This indicates that there are unique challenges to the use of currently available HER2-targeted therapies for the treatment of HER2-positive GC. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate consisting of an anti-HER2 human monoclonal IgG1 antibody with the same amino acid sequence as trastuzumab, an enzymatically cleavable peptide-based linker, and DXd, a novel topoisomerase I inhibitor, as its released payload. T-DXd has a high drug–antibody ratio (approximately 8) and a demonstrated bystander antitumor effect. It has demonstrated significant efficacy when compared with standard therapies and is approved as third- or later-line treatment for HER2-positive GC in Japan and second- or later-line treatment in the US. T-DXd treatment is associated with gastrointestinal and hematological adverse events, and a risk of interstitial lung disease (ILD), with the ILD risk being higher in Japan than in countries other than Japan. However, most adverse events, including ILD, can be managed with proactive monitoring and T-DXd dose modification, and initiation of adequate treatment. In this review, we summarize the discovery and development of T-DXd and provide guidance for T-DXd safety management, including ILD monitoring, for patients with HER2-positive GC.
Liposome display is a novel method for in vitro selection and directed evolution of membrane proteins. In this approach, membrane proteins of interest are displayed on liposome membranes through ...translation from a single DNA molecule by using an encapsulated cell-free translation system. The liposomes are probed with a fluorescence indicator that senses membrane protein activity and selected using a fluorescence-activated cell sorting (FACS) instrument. Consequently, DNA encoding a protein with a desired function can be obtained. By implementing this protocol, researchers can process a DNA library of 10(7) different mutants. A single round of the selection procedure requires 24 h for completion, and multiple iterations of this technique, which take 1-5 weeks, enable the isolation of a desired gene. As this protocol is conducted entirely in vitro, it enables the engineering of various proteins, including pore-forming proteins, transporters and receptors. As a useful example of the approach, here we detail a procedure for the in vitro evolution of α-hemolysin from Staphylococcus aureus for its pore-forming activity.
Microwave (MW) heating promotes various reactions catalyzed by supported metal nanoparticles (NPs); the mechanism is based on selectively heating the NPs, thereby inducing hot spots at the active ...reaction sites. Here, we demonstrate the effects of the sizes and loadings of platinum (Pt) NPs supported on single-crystal metal oxide (MOx) substrates (Al2O3, MgAl2O4, TiO2, SrTiO3) having different relative permittivities and conductivities. Considerable heating occurred when Pt NPs were deposited on MOx substrates having low relative permittivities and conductivities, indicating that the MW transparency of the substrate is the most critical parameter. Magnetic field heating was preferred when the loading amount of Pt NPs was large. Electromagnetic field simulations suggested that the electric field concentration between Pt NPs formed local hot spots. Moreover, the MW absorption behavior of the NP/MOx composite depended on the conductivity of the supported metal, and the frequency of the MWs. We conclude that the relative permittivity and conductivity of the MOx support are the most important parameters for ensuring efficacious MW heating by Pt NPs, followed by size and loading of the supported metal NPs. The synergistic effect of the metal NPs and MOx support results in targeted MW heating of the supported metal catalyst.
Abstract
The juvenile brain presents plasticity. Oligodendrocytes are the myelinating cells of the central nervous system and myelination can be adaptive. Plasticity decreases from juvenile to ...adulthood. The mechanisms involving oligodendrocytes underlying plasticity are unclear. Here, we show Na
+
-K
+
-Cl
–
co-transporter 1 (NKCC1), highly expressed in the juvenile mouse brain, regulates the oligodendrocyte activity from juvenile to adulthood in mice, as shown by optogenetic manipulation of oligodendrocytes. The reduced neuronal activity in adults was restored by
Nkcc1
overexpression in oligodendrocytes. Moreover, in adult mice overexpressing
Nkcc1
, long-term potentiation and learning were facilitated compared to age-matched controls. These findings demonstrate that NKCC1 plays a regulatory role in the age-dependent activity of oligodendrocytes, furthermore inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain.
Overexpression of enhancer of zeste homolog 2 (EZH2), an epigenetic repressor, occurs in various malignancies and is associated with poor prognosis; however, the functional role of EZH2 ...overexpression in cancer versus non‐cancerous tissue remains unclear. In this study, we found an inverse correlation between EZH2 and E‐cadherin gene expression in gastric cancer cells. Knockdown of EZH2 by short interfering RNA in gastric cancer cells resulted in a restoration of the E‐cadherin gene. We showed that the EZH2 complex existed with histone H3 and Lys27, which were methylated on E‐cadherin promoter regions in gastric cancer cells. The restoration of E‐cadherin was not involved in the change of the DNA methylation status in the E‐cadherin promoter region. Immunofluorescence staining confirmed the expression of E‐cadherin protein present in the cell membrane was restored after knockdown of EZH2, resulting in changing the cancer phenotype, such as its invasive capacity. In vivo, the relationship of inverse expression between EZH2 protein and E‐cadherin protein was observed at the individual cellular level in gastric cancer tissue. This study provides into the mechanisms underlying the functional role of EZH2 overexpression in gastric cancer cells and a new modality of regulation of E‐cadherin expression in silencing mechanisms of tumor suppressor genes. Our present study paves the way for exploring the blockade of EZH2 overexpression as a novel approach to treating cancer. (Cancer Sci 2008; 99: 738–746)
PDF
