Antigen-primed CD4^+CD25^+ Regulatory T Cells Prevent Skin Graft Rejection : in vitro and in vivo studies

原著論文Original PaperIn the present studies, we examined the role of regulatory T cells in developing strategies to achieve skin graft-specific tolerance and explored the immune characteristic of Treg cells and the main mechanisms through which inducing transplantation tolerance. The 5×10^4 Treg could inhibit the MLR obviously, and the effect of the Treg to the MLR is dose dependent. The suppression rate of Treg to response T cell from the donor was higher than control group that came from the non-donor, indicating that the suppression of Treg to response T cell was antigen specific. SR of Treg in co-culture was greater than that in separate culture, inferring that CD4^+CD25^+ Treg cells exerted their suppressive effects on effector T cells through cell to cell contact mechanism and cytokines secretion mechanism. In the group 1×10^5 Treg injected, the mean survive time of skin grafts from C57BL/6 mice was obviously longer than the control group. These data suggest that antigen-primed CD^4+CD25^+Treg are effective therapeutic tool to prevent skin allograft rejection

ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

揭示了在外界能量供应缺乏时，细胞通过激活ULK1来介导葡萄糖分解代谢重编程以维持胞内的能量与氧化还原稳态的详细机制，并创新地发现了ULK1独立于自噬的关键功能。基于自噬和糖代谢与人类健康的重要相关性，该研究将很可能为我们预防和治疗各类代谢疾病提供新的思路和药物靶点。Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.State Key Program of National Natural Science of China， the 973 Program；National Natural Science Foundation of China for Fostering Talents in Basic Research ；the Foundation for Innovative Research Groups of the National Natural Science Foundation of China； and the 111 Project of Education of China

Investigation of Low-Sidelobe Beampattern Controlling Methods for Acoustic Transmitting Array of Underwater Vehicles

In underwater unmanned vehicles, complex acoustic transducer arrays are always used to transmitting sound waves to detect and position underwater targets. Two methods of obtaining low-sidelobe transmitting beampatterns for acoustic transmitting arrays of underwater vehicles are investigated. The first method is the boundary element model optimization method which used the boundary element theory together with the optimization method to calculate the driving voltage weighting vector of the array. The second method is the measured receiving array manifold vector optimization method which used the measured receiving array manifold vectors and optimization method to calculate the weighting vector. Both methods can take into account the baffle effect and mutual interactions among elements of complex acoustic arrays. Computer simulation together with experiments are carried out for typical complex arrays. The results agree well and show that the two methods are both able to obtain a lower sidelobe transmitting beampattern than the conventional beamforming method, and the source level for each transmitting beam is maximized in constraint of the maximum driving voltage of array elements being constant. The effect of the second method performs even better than that of the first method, which is more suitable for practical application. The methods are very useful for the improvement of detecting and positioning capability of underwater unmanned vehicles

Incentive design with customer satisfaction for business process outsourcing: multi-task

We study the incentive design decision of a firm that outsources its online marketing and operational business lines to professional external and internal service providers under the principalagent framework. Customer satisfaction is represented as the composite of the agents’ sales and quality-control efforts via the disconfirmation model, and is introduced into the demand model and incentive contracts. Two scenarios corresponding to whether the brand owner delegates business to a single agent or to multiple agents are studied. We derive the brand owner’s optimal contracts and the agents’ effort levels and conduct extensive sensitivity analyses regarding the influences of model parameters. We find that increases in the measure accuracy of customer satisfaction can bring significant benefit to the firm’s profitability, and explore how it is affected by system factors. Specifically, the benefit is more substantial when the marginal cost of quality-control effort is relatively smaller than the marginal cost of sales effort. An interesting discovery is that the brand owner always earns more profit by outsourcing business to multiple agents than to a single agent, mainly because of his inflexibility in reaching a balance between inducing higher effort levels and providing a sufficient risk premium in the singe-agent case. This profit gap can be expanded by incentivizing both agents on customer satisfaction measures, and is shown quite significant under certain settings in the numerical studies

Customer incentive rebalancing plan in free-float bike-sharing system with limited information

Free-float bike-sharing (FFBS) systems have increased in popularity as a sustainable travel mode in recent years, especially in the urban areas of China. Despite the convenience such systems offer to customers, it is not easy to maintain an effective balance in the distribution of bikes. This study considers the dynamic rebalancing problem for FFBS systems, whereby user-based tactics are employed by incentivizing users to perform repositioning activities. Motivated by the fact that the problem is frequently faced by FFBS system operators entering a new market with limited information on travel demand, we adopt the ranking and selection approach to select the optimal incentive plan. We describe the system dynamics in detail, and formulate a profit maximization problem with a constraint on customer service level. Through numerical studies, we first establish that our procedure can select the optimal incentive plan in a wide range of scenarios. Second, under our incentive plan, the profit and service level can be improved significantly compared with the scenario without incentive provision. Third, in most cases, our procedure can achieve the optimal solution with a reasonable sample size. Keywords: free-float bike-sharing; customer incentive-based rebalancing; simulation optimization; ranking and selectio

Evaluation of the Teaching Quality and Ability of Hospital Administrators by Overseas Distinguished Teachers

In recent years, China has been actively promoting the Belt and Road Initiative. In the context of the gradual opening of the medical market, it is urgent to improve the health management knowledge and scientific research capabilities of the hospital administrators, further enhance the hospital management level, so that the hospitals can obtain a greater edge in the international medical competition. Using overseas intelligence to promote the internationalization of education is one of the important means. The Affiliated Cancer Hospital and Institute of Guangzhou Medical University has invited Portuguese management professors to establish an academic and educational cooperation relationship, and invited them to offer training for hospital administrators. This article uses questionnaires to survey the trainees participating in this training and evaluates the teaching quality of overseas teachers. The results showthat the interviewed students generally present high affirmation to the training effects of the training courses and the teaching quality of overseas distinguished teachers

Vasa Is a Potential Germ Cell Marker in Leopard Coral Grouper (<i>Plectropomus leopardus</i>)

Vasa (Ddx4, DEAD box polypeptide 4), an extremely specific marker of germ cells in vivo, is an ATP-dependent RNA helicase that plays an essential role in germ cell development and gametogenesis. However, the expression and function information about this gene in groupers remains lacking. Here, vasa homolog termed Plvasa was isolated and identified Plvasa as a putative germ cell marker in the leopard coral grouper, (Plectropomus leopardus). Results indicated that Plvasa contained 17 exons in the genomic sequence and 9 conserved motifs of the DEAD-box protein by sequence analysis. The sequence comparison, phylogenetic analyses and synteny analyses showed that Plvasa was homologous with other teleosts. Additionally, the expression of Plvasa was significantly higher in gonads than in other tissues in adult individuals (p Plvasa revealed that it was only expressed in the germ cells, such as spermatids, germline stem cells and oocytes at different stages, and could not be detected in the somatic cells of gonads. The current study verified that the Plvasa gene is a valuable molecular marker of germ cells in leopard coral grouper, which potentially plays an important role in investigating the genesis and development of teleost germ cells