•We provide a life cycle cost analysis for a degrading system.•We consider a multi-dimensional degradation process.•We consider the influence of degradation dependence and environmental variations.
...This paper presents a life cycle cost model for systems subject to multiple dependent degradation processes and environmental influence. Different from most existing studies that assume an infinite time horizon for cost analysis, we evaluate the life cycle cost within a finite horizon. The system is subject to multiple degradation processes, among which the dependence is described via copula. In addition to the stochastic dependence of the degradation processes, the health condition of the system is influenced by the operating environment. The environmental influence on the system condition lies in two aspects: It accelerates or decelerates the degradation processes and meanwhile leads to a random failure threshold. System reliability considering multiple dependent degradation processes and environmental influence is assessed as the first step, followed by the life cycle cost analysis. A numerical example is presented to illustrate the proposed model.
Ferroptosis is primarily triggered by a failure of the glutathione (GSH)-glutathione peroxidase 4 (GPX4) reductive system and associated overwhelming lipid peroxidation, in which enzymes regulating ...polyunsaturated fatty acid (PUFA) metabolism, and in particular acyl-CoA synthetase long chain family member 4 (ACSL4), are central. Here, we found that exogenous oxygen radicals generated by photodynamic therapy (PDT) can directly peroxidize PUFAs and initiate lipid autoxidation, coinciding with cellular GSH depletion. Different from canonical ferroptosis induced by RSL3 or erastin, PDT-initiated lipid peroxidation and ferroptotis-like cell death is independent of lipoxygenase (ALOXs) and ACSL4. Especially, this form of cell death modality can be triggered in malignant cells insensitive to or acquired resistance to canonical ferroptosis inducers. We also observed a distinct iron metabolism pathway in this PDT-triggered cell death modality, in which cytosolic labile iron is decreased probably due to its relocation to mitochondria. Inhibition of the mitochondrial Ca2+ and Fe2+ uniporter (MCU) effectively prevented PDT-triggered lipid peroxidation and subsequent cell death. Therefore, we tentatively term this distinct ferroptosis-like cell death as liperoptosis. Moreover, using the clinically approved photosensitizer Verteporfin, PDT inhibited tumor growth through inducing prevailing ferroptosis-like cell death in a mouse xenograft model. With its site-specific advantages, these findings highlight the value of using PDT to trigger lipid peroxidation and ferroptosis-like cell death in vivo, and will benefit exploring the exact molecular mechanism of immunological effects of PDT in cancer treatment.
Elevated lipid peroxidation (LPO), usually present in the tumour microenvironment (TME), is profoundly implicated in antitumour immunity and may be targeted for the development of new antitumour ...therapies. However, tumour cells may also rewire their metabolism to survive elevated LPO. Here, we report a novel and nonantioxidant mechanism by which tumour cells benefit from accumulated cholesterol to restrain LPO and ferroptosis, a nonapoptotic form of cell death characterized by accumulated LPO. Modulating cholesterol metabolism, especially LDLR-mediated cholesterol uptake, shifted the susceptibility of tumour cells to ferroptosis. Elevation of cellular cholesterol content specifically restrained LPO triggered by GSH-GPX4 inhibition or oxidizing factors in the TME. Furthermore, depletion of TME cholesterol by MβCD efficiently enhanced the antitumour efficacy of ferroptosis in a mouse xenograft model. Distinct from the antioxidant effect of its metabolic intermediates, the protective role of cholesterol was ascribed to its ability to decrease membrane fluidity and promote lipid raft formation, which affects the diffusion of LPO substrates. A correlation between LPO and lipid rafts was also found in tumour tissues from renal cancer patients. Together, our findings have identified a general and nonsacrificial mechanism by which cholesterol suppresses LPO, which can be exploited to enhance the efficacy of ferroptosis-based antitumour strategies.
•Cholesterol accumulation shifts the susceptibility of tumour cells to lipid peroxidation and ferroptosis.•Cholesterol restrains lipid peroxidation by decreasing membrane fluidity and promoting lipid raft formation.•Depletion of TME cholesterol enhances the antitumour efficacy of ferroptosis.•Lipid peroxidation correlates with lipid rafts in vivo.
A highly efficient microprojectile transformation system for sorghum (
Sorghum bicolor
L.) has been developed by using immature embryos (IEs) of inbred line Tx430. Co-bombardment was performed with ...the neomycin phosphotransferase
II
(
nptII
) gene and the green fluorescent protein (
gfp
) gene, both under the control of the maize ubiquitin1 (
ubi
1) promoter. After optimization of both tissue culture media and parameters of microprojectile transformation, 25 independent transgenic events were obtained from 121 bombarded IEs. The average transformation frequency (the total number of independent transgenic events divided by the total number of bombarded IEs) was 20.7% in three independent experiments. Transgenic events were confirmed by both PCR screening and Southern hybridization of genomic DNA from primary transgenics (T
0
). More than 90% of transformants were fertile and displayed normal morphology in a containment glasshouse. Co-transformation rate of the
nptII
and
gfp
genes was 72% in these experiments. The segregation of
nptII
and
gfp
in T
1
progenies was observed utilizing fluorescence microscopy and geneticin selection of seedlings indicating both were inherited in the T
1
generation. The transformation procedure, from initiating IEs to planting putative transgenic plantlets in the glasshouse, was completed within 11–16 weeks, and was approximately threefold more efficient than the previously reported best sorghum transformation system.
We describe an operationally simple transition-metal-free borylation of alkyl iodides. This method uses commercially available diboron reagents as the boron source and exhibits excellent functional ...group compatibility. Furthermore, a diverse range of primary and secondary alkyl iodides could be effectively transformed to the corresponding alkylboronates in excellent yield. Mechanistic investigations suggest that this borylation reaction proceeds through a single-electron transfer mechanism featuring the generation of an alkyl radical intermediate.
The construction of molecularly imprinted polymers on magnetic nanoparticles gives access to smart materials with dual functions of target recognition and magnetic separation. In this study, the ...superparamagnetic surface-molecularly imprinted nanoparticles were prepared via surface-initiated reversible addition–fragmentation chain transfer (RAFT) polymerization using ofloxacin (OFX) as template for the separation of fluoroquinolones (FQs). Benefiting from the living/controlled nature of RAFT reaction, distinct core–shell structure was successfully constructed. The highly uniform nanoscale MIP layer was homogeneously grafted on the surface of RAFT agent TTCA modified Fe3O4@SiO2 nanoparticles, which favors the fast mass transfer and rapid binding kinetics. The target binding assays demonstrate the desirable adsorption capacity and imprinting efficiency of Fe3O4@MIP. High selectivity of Fe3O4@MIP toward FQs (ofloxacin, pefloxacin, enrofloxacin, norfloxacin, and gatifloxacin) was exhibited by competitive binding assay. The Fe3O4@MIP nanoparticles were successfully applied for the direct enrichment of five FQs from human urine. The spiked human urine samples were determined and the recoveries ranging from 83.1 to 103.1% were obtained with RSD of 0.8–8.2% (n = 3). This work provides a versatile approach for the fabrication of well-defined MIP on nanomaterials for the analysis of complicated biosystems.
Retrospective analysis of patients undergoing cancer surgery suggests the use of regional anesthesia may reduce cancer recurrence and improve survival. Amide-linked local anesthetics have ...antiinflammatory properties, although the mechanism of action in this regard is unclear. As inflammatory processes involving Src tyrosine protein kinase and intercellular adhesion molecule-1 are important in tumor growth and metastasis, we hypothesized that amide-linked local anesthetics may inhibit inflammatory Src-signaling involved in migration of adenocarcinoma cells.
NCI-H838 lung cancer cells were incubated with tumor necrosis factor-α in absence/presence of ropivacaine, lidocaine, or chloroprocaine (1 nM-100 μM). Cell migration and total cell lysate Src-activation and intercellular adhesion molecule-1 phosphorylation were assessed. The role of voltage-gated sodium-channels in the mechanism of local anesthetic effects was also evaluated.
Ropivacaine treatment (100 μM) of H838 cells for 20 min decreased basal Src activity by 62% (P=0.003), and both ropivacaine and lidocaine coadministered with tumor necrosis factor-α statistically significantly decreased Src-activation and intercellular adhesion molecule-1 phosphorylation, whereas chloroprocaine had no such effect. Migration of these cells at 4 h was inhibited by 26% (P=0.005) in presence of 1 μM ropivacaine and 21% by 1 μM lidocaine (P=0.004). These effects of ropivacaine and lidocaine were independent of voltage-gated sodium-channel inhibition.
This study indicates that amide-, but not ester-linked, local anesthetics may provide beneficial antimetastatic effects. The observed inhibition of NCI-H838 cell migration by lidocaine and ropivacaine was associated with the inhibition of tumor necrosis factor-α-induced Src-activation and intercellular adhesion molecule-1 phosphorylation, providing the first evidence of a molecular mechanism that appears to be independent of their known role as sodium-channel blockers.
PurposeThis study explores how sharing platforms achieve platform loyalty through various operation management strategies.Design/methodology/approachA multiple case study method has been conducted in ...two Chinese sharing economy industries: ride- and bike-sharing. Data were collected through 30 semi-structured interviews with managers from four platform companies (DiDi, Uber China, ofo and Mobike). Individual case studies were developed from the triangulation of all existing data. Concurrent with the development of these individual case studies was a cross-case analysis. Emerging patterns have been identified and compared to previous findings in the literature to build upon and modify the existing knowledge base and to formulate a series of propositions.FindingsPlatform asset characteristics and mergers and acquisitions affect supply network readiness and operational capacity, respectively, and this effect would consequently contribute to achieving platform loyalty through user satisfaction. Moreover, externality, as a moderator, may influence the strength of the relationship between satisfaction and platform loyalty.Practical implicationsThe proposed theoretical model provides an overarching framework for sharing platform companies to design and operate their businesses while carefully examining the situations, contexts and actions of users and other stakeholders and choosing an appropriate strategic mechanism to drive platform growth.Originality/valueThis study is one of the first to empirically explain how firms in a sharing economy sector could gain platform loyalty by adopting an expectation–confirmation theory perspective.
An increase of the Mo content from 0.43% to 1.06% has been tried so as to increase the strength level of the 3Ni–Cr–Mo–V martensitic steels from 1300MPa to 1500MPa. Hydrogen embrittlement ...susceptibility of the two steels after quenching and 575°C tempering has been evaluated by means of slow strain rate tests. Results show that the reduction of area of the two steels decreases with increasing hydrogen concentration in an identical linear manner, indicating that hydrogen embrittlement susceptibility does not increase with the increase of the strength level from 1300MPa to 1500MPa. When hydrogen content reaches a critical value, a drastic decrease in the ductility has been found for both steels, with the fracture mode varying from ductile to intergranular fracture. The critical hydrogen concentration of the 1.06% Mo steel is about 3wppm higher than that of the 0.43% Mo steel. Results of thermal desorption spectroscopy analysis indicate that there is some hydrogen in the steels that is not easy to diffuse during exposure at room temperature, which is presumably trapped by M2C carbides. It is found that the higher critical hydrogen concentration of the 1.06% Mo steel is related to a higher amount of M2C carbides due to its higher Mo content.
Hydrogen trapping behavior has been investigated by means of thermal desorption spectrometry (TDS) for a high strength steel after it is austenitized at the temperature range of 880–1250 °C, oil ...quenched, and tempered at 200 °C. Results show that with increasing austenitizing temperature, the pre-charged hydrogen concentration in the steel first decreases and then increases, being the lowest value at the austenitizing temperature of 1050 °C. The variation of hydrogen concentration with austenitizing temperature is related to the differences in the prior austenite grain size and solute Nb content, which may act as shallow hydrogen traps in the steel. The difference in the pre-charged hydrogen concentration can account for the previously reported result on delayed fracture resistance of the steel after austenitized at different temperatures.
•Hydrogen trapping was investigated by TDS for a steel austenitized at 880–1250 °C.•Hydrogen concentration varies non-monotonically with austenitizing temperature.•Hydrogen concentration in the steel is the lowest at 1050 °C austenitizing.•The variation is related to the prior austenite grain size and solute Nb content.•Grain boundary and Nb solute atom may act as shallow hydrogen traps in the steel.
PDF
