Endoplasmic Reticulum Stress-Mediated Apoptosis Involved in Indirect Recognition Pathway Blockade Induces Long-Term Heart Allograft Survival

Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effectively knock down CD80 and CD86 expression. T cells primed by these DCs inhibited allogeneic responses. Administration of recipient DCs loaded with alloantigen after CD80 and CD86 blockade prolonged cardiac allograft survival. We also found a higher percentage of apoptotic T cells in lymph tissues and grafts than that detected in control group. In addition, these T cells expressed high expression of GRP78 than controls, indicating activation of unfolded protein responses. Upregulation of CHOP expression among these cells suggested that the endoplasmic reticulum stress (ERS) response switched to a proapoptotic response. Our results indicated that ERS-induced apoptosis may be involved in allogeneic T-cell apoptosis, and the ERS-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of allograft rejection

Myeloid-Derived Suppressor Cells Participate in Preventing Graft Rejection

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells and have a tremendous potential to suppress immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection, transplantation, and other pathological conditions and can potently suppress T-cell function. Here, we discuss recent findings that describe the molecular mechanisms of MDSCs suppressing T-cell immune responses as well as recent observations that MDSCs may have roles in transplant tolerance

Chance-constrained optimization of storage and PFC capacity for railway electrical smart grids considering uncertain traction load

To foster the utilization of regeneration braking energy and suppress voltage unbalance (VU), a railway electrical smart grid (RESG), intergraded with power flow controller (PFC) and energy storage (ES), is proposed as an important part of next-generation electrified railways. However, under the uncertain traction load, how to design the optimal size of PFC-ES is a challenge during the planning period. Hence, this paper proposes a chance-constrained two-stage programming approach. The first-stage aims to minimising the overall cost of RESG’s devices. The second-stage aims to arrange the energy flow of the PFC-ES with the objective of minimising the expected operation cost under the dynamic VU restriction, and the stochastics characteristics of traction load are transformed into a chance constraint by using a scenario approach. Then, traction power predictions are combined with multivariate Gaussian Mixture Model (multi-GMM) model to generate correlated traction power flow scenarios and to assess VU probabilistic metrics distribution with different confidence levels. Finally, a novel algorithm is designed to select the confidence level and violation probability so that the capacity planning results can ensure the high-efficient and high-quality operation of the RESG. Case studies based on an actual electrified railway demonstrate that the proposed PFC-ES sizing approach can reduce the overall cost by up to 13%

The SPB-Box Transcription Factor AaSPL2 Positively Regulates Artemisinin Biosynthesis in Artemisia annua L.

Artemisinin, an important compound produced by Artemisia annua, is the active ingredient in the treatment of malaria. Jasmonic acid, one of the phytohormones, is an important elicitor of artemisinin biosynthesis by enhancing transcription levels of transcription factors. SPL transcription factors are plant-specific transcription factors of plant growth, development, and secondary metabolism regulation. However, to date, the SPL transcription factors that regulate artemisinin biosynthesis is currently unclear. Here, we show that an SPL transcription factor can positively regulate artemisinin biosynthesis by binding to the promoter of artemisinin biosynthetic pathway genes. We screened AaSPL2 by gene expression profiles analysis in 14 SPL transcription factors. We demonstrated that AaSPL2 can activate the promoter of DBR2 by dual-LUC assy. Moreover, in the AaSPL2 overexpression plants, the artemisinin content was increased by 33–86%, and in the AaSPL2 -RNAi transgenic plants, artemisinin content was decreased by 33–65%. These data suggest that AaSPL2 and DBR2 interact with a “GTAC” cis-element in the DBR2 promoter, mediating the transcriptional activation of DBR2 in response to JA and resulting in the improvement on artemisinin content

Molecular cloning and functional characterization of BcTSA in the biosynthesis of indole alkaloids in Baphicacanthus cusia

Baphicacanthus cusia (Nees) Bremek (B. cusia) is an essential traditional Chinese herb that is commonly used to treat colds, fever, and influenza. Indole alkaloids, such as indigo and indirubin, are the primary active constituents of B. cusia. The indole-producing reaction is crucial for regulating the flow of indole alkaloids metabolites along the pathways and coordinating primary and secondary product biosynthesis in plants. The tryptophan synthase alpha-subunit (TSA) can catalyse a process that produces indole, which is free to enter secondary metabolite pathways; however, the underlying potential mechanism of regulating indigo alkaloids synthesis remains unknown. Here, a BcTSA was cloned from the transcriptome of B. cusia. The BcTSA has a significant degree of similarity with other plant TSAs according to bioinformatics and phylogenetic analyses. Quantitative real-time PCR (RT-qPCR) research showed that BcTSA was dramatically enhanced in response to treatment with methyl jasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA), and was predominantly expressed in the stems as opposed to the leaves and rhizomes. Subcellular localization revealed that BcTSA is localized in chloroplasts, which is compatible with the fact that the conversion of indole-3-glycerol phosphate (IGP) to indole occurs in chloroplasts. The complementation assay results showed that BcTSA was functional, demonstrating that it was capable of catalyzing the conversion of IGP to indole. BcTSA was shown to stimulate the manufacture of indigo alkaloids including isatin, indigo, and indirubin when the gene was overexpressed in the hairy roots of Isatis indigotica. In conclusion, our research provides novel perspectives that might be applied to manipulating the indole alkaloid composition of B. cusia

Nonepitaxial Gold-Tipped ZnSe Hybrid Nanorods for Efficient Photocatalytic Hydrogen Production

For the first time, colloidal gold (Au)–ZnSe hybrid nanorods (NRs) with controlled size and location of Au domains are synthesized and used for hydrogen production by photocatalytic water splitting. Au tips are found to grow on the apices of ZnSe NRs nonepitaxially to form an interface with no preference of orientation between Au(111) and ZnSe(001). Density functional theory calculations reveal that the Au tips on ZnSe hybrid NRs gain enhanced adsorption of H compared to pristine Au, which favors the hydrogen evolution reaction. Photocatalytic tests reveal that the Au tips on ZnSe NRs effectively enhance the photocatalytic performance in hydrogen generation, in which the single Au-tipped ZnSe hybrid NRs show the highest photocatalytic hydrogen production rate of 437.8 µmol h−1 g−1 in comparison with a rate of 51.5 µmol h−1 g−1 for pristine ZnSe NRs. An apparent quantum efficiency of 1.3% for hydrogen evolution reaction for single Au-tipped ZnSe hybrid NRs is obtained, showing the potential application of this type of cadmium (Cd)-free metal–semiconductor hybrid nanoparticles (NPs) in solar hydrogen production. This work opens an avenue toward Cd-free hybrid NP-based photocatalysis for clean fuel production.W.C. and X.L. contributed equally to this work. This work was supported by the Australian Research Council (ARC) Discovery Early Career Researcher Award (DECRA) (DE 160100589) and discovery project (DP 170104264). Y.L. acknowledges support from the NSFC (grant no. 11674131). W.C. acknowledges the scholarship from the China Scholarship Council

Colloidal quasi-one-dimensional dual semiconductor core/shell nanorod couple heterostructures with blue fluorescence

Herein we report a nanorod couple heterostructure made of dual semiconductors, in which two parallelly aligned ZnSe nanorods are connected by the growth of ZnS on both end and side facets, producing hetero-ZnS (short arms)–ZnSe (long arms)/ZnS shell nanorod couples. As evidenced by electronic structure studies, both experimental and theoretical, such core/shell nanorod couple heterostructures can act as a platform to precisely tailor the quantum confinement of charge carriers between the constituting components within a single nano-object, generating blue fluorescence after the overgrowth of an alloyed ZnCdS layer on the heterostructures. We foresee the mechanistic insights gained and electronic structures revealed in this work would shed light on the rational design of more complex heterostructures with novel functionalities.This work was supported by the Australian Research Council (ARC) Discovery Early Career Researcher Award (DECRA) (Project ID: DE160100589), and the National Natural Science Foundation of China (Grant No. 21701015 and 21811530054)