Extracellular vesicles (EVs) are nanovesicles involved in multiple biological functions. Small EVs (sEVs) are emerging as therapeutics and drug delivery systems for their contents, natural carrier ...properties, and nanoscale size. Despite various clinical application potentials, little is known about the effects of storage conditions on sEVs for functional analysis and therapeutic use. In this study, we evaluated the stability of sEVs stored at 4 °C, −20 °C, and −80 °C up to 28 days and compared them to fresh sEVs. Also, the effect of freeze-thawing circles on the quantity of sEVs was assessed. We found that different storage temperatures, along with shelf life, impact the stability of sEVs when compared to freshly isolated sEVs. Storage changes the size distribution, decreases quantity and contents, and impacts cellular uptake and biodistribution of sEVs. For functional studies, isolated sEVs are suggested to be analyzed freshly or stored at 4 °C or −20 °C for short-term preservation depending on study design; but −80 °C condition would be more preferable for long-term preservation of sEVs for therapeutic application.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The paper investigates pricing/ordering issues in a dyadic supply chain, in which a core supplier sells products through a budget-constrained retailer. The retailer faces stochastic demand and is ...fairness-concerned as well. If needed, the retailer can get financing support from bank by means of buyback guarantee financing (BGF) mode, which is often used in China. By introducing Nash bargaining solution as the fairness reference point, we formulate the retailer's fairness-concerned utility function and develop a two-echelon pricing/ordering game model. We then study the combined impacts of fairness concerns and BGF on two members' equilibrium strategies and supply chain performance. We also discuss the corresponding issues under no budget constraint, no financing service and bank financing. Our results show that: (1) two members' equilibrium strategies are significantly influenced by the retailer's fairness-concerned behaviour and initial budget; (2) as compared to no budget constraint, BGF can bring the whole supply chain more performance, which means that BGF can yield value-added; (3) When the retailer takes the risk of uncertain market solely, the retailer's fairness concerns are beneficial for supply chain to improve the performance.
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BFBNIB, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Investigating a cooperative advertising problem mixed with production/ordering planning.•Considering the agents in the supply chain have different risk attitudes.•Measuring the agents’ risk through ...the CVaR approach.•Revealing the effect of demand uncertainty and the two agents’ risk aversion.
This paper considers a cooperative advertising and ordering issue in a two-echelon supply chain in which a risk-averse manufacturer sells a product through a risk-averse retailer. We assume that demand for the product is a random variable influenced by the manufacturer's global advertising and the retailer's local advertising. To stimulate demand for the product, the risk-averse manufacturer induces the risk-averse retailer to increase local advertising expenditure through cooperative advertising contracts. With the objective of maximizing conditional value-at-risk, models for determining the retailer's optimal order quantity and both agents’ advertising investments are developed for both centralized and decentralized settings. We reveal the effect of demand uncertainty and two agents’ risk aversion on both agents’ optimal advertising/ordering policies. Through both theoretical and numerical analyses, we find that: 1) the centralized scenario may perform worse than the decentralized one in many cases if the decision-maker of the centralized supply chain is more risk averse than its two participants; 2) whether the risk-averse manufacturer is willing to share the retailer's local advertising expenditure depends significantly on the degree of two agents' risk aversion; and 3) in the decentralized setting, it will be more beneficial for both agents that the leader is more risk averse than the follower. These new findings are further supplements to the results in the existing related literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Polyimide (PI) is one of the best engineering plastics with excellent thermal, mechanical, dielectric performance and chemical stability. Among various PI products, film is one of the most dominant ...types. If PI films are to be applied to optical devices and display equipment, it is necessary to improve their optical transparency in the ultraviolet–visible region. However, improving the optical transparency of PI films would affect their thermal performance including thermal and dimensional stability. Therefore, how to balance optical and thermal performance to obtain highly transparent PI films with the best overall performance becomes a focus of current research field. In this review, we categorize transparent PI films into highly transparent PI, transparent PI with high glass transition temperature (Tg) and transparent PI with low coefficient of thermal expansion (CTE) based on their optical and thermal properties. Then, we review research progress in the field of polymer molecular design including synthesis strategies and properties in recent 5 years, to inspire research ideas and elaborate on the possible ways to develop high‐performance, colorless and transparent PI materials.
Building high‐performance colorless and transparent polyimide (PI) films at the molecular level requires balancing the light transmittance, thermal stability, dimensional stability and other properties of PIs. The main strategy is to inhibit the formation of charge transfer complexes intermolecularly and intramolecularly, and to improve the rigidity of the molecule. This review focuses on how to achieve this goal.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
CD8
T cells play a critical role in the innate antitumour immune response. Recently, CD8
T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer ...(NSCLC). However, the molecular biological mechanisms of CD8
T cell dysfunction in human NSCLC are still unclear.
The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8
T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8
T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined.
The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8
T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8
T cells. Furthermore, circUSP7 inhibits CD8
T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients.
Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8
T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predicting energy demand is of great significance for governments to formulate energy policies and adjust industrial structures. Energy data, such as demand of natural gas, are small samples. In this ...paper, data with small sample size, nonlinearity, randomness and fuzzy influence factors are considered. A least squares support vector machine model based on grey related analysis (GRA-LSSVM) is proposed, and weighted adaptive second-order particle swarm optimization algorithm (WASecPSO) is designed to optimize the model’s parameters. The second-order particle swarm optimization (SecPSO) algorithm updates particles velocity and position weights dynamically, which can balance global search ability and local improvement, and further improve the accuracy of optimization. In addition, the GRA-LSSVM optimized by the WASecPSO algorithm predicts the annual consumption of natural gas in China. The results show that GRA-LSSVM has better generalization ability and training effect, and GRA-LSSVM optimized by WASecPSO algorithm has higher prediction accuracy than PSO algorithm and SecPSO algorithm optimized model.
•In order to eliminate redundant information on LS-SVM modeling, the GRA-LSSVM model is proposed.•Weight adaptive SecPSO algorithm is proposed to optimize the parameters of GRA-LSSVM model.•Experiments with China’s natural gas consumption data prove that WASecPSO-GRA-LSSVM is superior to other models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Allergic rhinitis (AR) is a common allergic disorder, afflicting thousands of human beings. Aberrant mitochondrial dynamics are important pathological elements for various immune cell dysfunctions ...and allergic diseases. However, the connection between mitochondrial dynamics and AR remains poorly understood. This study aimed to determine whether mitochondrial dynamics influence the inflammatory response in AR.
In the present study, we established a murine model of AR by sensitization with ovalbumin (OVA). Then, we investigated the mitochondrial morphology in mice with AR by transmission electron microscopy and confocal fluorescence microscopy, and evaluated the role of Mdivi-1 (an inhibitor of mitochondrial fission) on allergic symptoms, inflammatory responses, allergic-related signals, and reactive oxygen species formation.
There was a notable enhancement in mitochondrial fragmentation in the nasal mucosa of mice following OVA stimulation, whereas Mdivi-1 prevented aberrant mitochondrial morphology. Indeed, Mdivi-1 alleviated the rubbing and sneezing responses in OVA-sensitized mice. Compared with vehicle-treated ones, mice treated with Mdivi-1 exhibited a reduction in interleukin (IL)-4, IL-5, and specific IgE levels in both serum and nasal lavage fluid, and shown an amelioration in inflammatory response of nasal mucosa. Meanwhile, Mdivi-1 treatment was associated with a suppression in JAK2 and STAT6 activation and reactive oxygen species generation, which act as important signaling for allergic response.
Our findings reveal mitochondrial dynamics modulate the allergic responses in AR. Mitochondrial dynamics may represent a promising target for the treatment of AR.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
In this paper, we discuss how a capital-constrained retailer determines his optimal advertising/ordering policy and selects his financing mode when he faces the following modes: no financing service, ...bank financing, and supplier/mixed financing. For each mode, we construct an optimization model and present a method for how the retailer determines his corresponding optimal advertising and ordering policies in the terms of his initial capital level. Furthermore, we derive the conditions of retailer selecting the optimal financing mode based on both his initial capital level and the interest rates of the financing services. We show that when the retailer is relatively “poor,” he prefers bank financing mode if the bank interest rate is lower than the supplier, otherwise mixed financing mode; when he is moderately “rich,” he only selects supplier financing mode if the bank interest rate is greater than a threshold value and otherwise bank financing mode; however, when he is relatively “rich,” he always chooses bank financing mode even if the bank interest rate is higher than the supplier. We conduct numerical studies to illustrate the theoretical results and find adopting financing service significantly improves the retailer’s performance especially when he has relatively low initial capital level.
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BFBNIB, CEKLJ, GIS, IJS, KISLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In the framework of the newsvendor model, both single- and multi-period models are proposed to investigate the ordering strategy of a risk-averse retailer under buyback guarantee financing (BGF) and ...stochastic demand. In the single-period model, the classical newsvendor is extended by introducing risk aversion and capital constraints simultaneously. It is found that the optimal ordering quantity is a monotonic function in some parameters, such as increasing in the retailer's risk aversion and salvage value, while decreasing in the initial capital and wholesale price. The multi-period model is a dynamical model described by the bounded rationality decision adjustment rules. We then investigate the complex dynamics they admit, such as period-doubling bifurcation and chaotic phenomena, and have found that the dynamical models experience more complex behaviour than their static counterpart. Furthermore, in the dynamical case, we could see periodic, bifurcating or chaotic changes in ordering quantity. We also investigate the influence of BGF on ordering quantity, which may lead to a risk-averse retailer to order aggressively. Finally, some numerical simulations are given to illustrate the theoretical results and some suggestions are also provided.
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BFBNIB, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•We explore the relative value of completely joint liability financing over individual financing.•We prove the existence of equilibrium point for two firms with joint liability.•We compare the two ...financing schemes from the perspective of the firms and the bank.•We show insights for the bank how to set its financing term under completely joint liability financing.
This paper makes an attempt to explore the relative value of a completely joint liability (CJL) financing scheme over traditional individual financing scheme for two financially-constrained firms. We develop a risk-sharing non-cooperative Nash-game model for the two firms in which they make unilateral ordering and financial decisions based on the CJL financing agreement as to the additional benefit (i.e., unit financing cost reduction) because of joint liability. We prove the existence of the firms’ equilibrium inventory decisions in a Nash game that is in general not quasi-concave or even supermodular. We show that in equilibrium, the completely joint liability of CJL financing induces the two firms to order more (compared to individual financing case), and meanwhile, the firms become more aggressive in ordering as the shared risk goes up. However, such over-investment in ordering under CJL financing does not always result in higher bankruptcy risks for the firms. Importantly, we show that the choice of the proposed financing schemes for both the firms is completely determined by a simple two-threshold policy in terms of the firms’ initial capitals and loan terms, and provide insights on how a financing-need firm to select proper partners to use CJL financing together, and how a profit-seeking bank to strategically set the proper financing terms to make the CJL financing scheme generate more benefits to itself and the two firms simultaneously (i.e., “win-win-win” situation).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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