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Under stress hematopoiesis, previous studies have suggested the migration of hematopoietic stem cells (HSCs) from bone marrow (BM) to extramedullary sites such as the spleen. However, there is little direct evidence of HSC migration from the BM to the spleen. Here, we induced myeloablation via 5-fluorouracil (5-FU) and showed direct evidence of HSC migration from BM to spleen during hematopoietic regeneration via a photoconvertible fluorophore. Moreover, during steady state, HSCs preferentially migrated to BM rather than spleen, but during hematopoietic regeneration, HSCs preferred spleen as a migration site equivalently or greater. Furthermore, in the early phase, HSCs egressed from BM through the attenuated HSC retention. However, HSCs in the late phase gained significantly enhanced cell-autonomous motility, which was independent of chemotaxis. Collectively, HSC mobilization from BM, before the migration to the spleen, was dynamically changed from passive to active events during hematopoietic regeneration. • Endogenous BM HSCs are mobilized to the spleen during hematopoietic regeneration. • Early-phase HSCs passively egress from BM through attenuation of their retention. • Late phase HSCs gain greater cell-autonomous motility, independent of chemotaxis. [ABSTRACT FROM AUTHOR]

Therapeutic neoantigen cancer vaccines have limited clinical efficacy to date. Here, we identify a heterologous prime-boost vaccination strategy using a self-assembling peptide nanoparticle TLR-7/8 agonist (SNP) vaccine prime and a chimp adenovirus (ChAdOx1) vaccine boost that elicits potent CD8 T cells and tumor regression. ChAdOx1 administered intravenously (i.v.) had 4-fold higher antigen-specific CD8 T cell responses than mice boosted by the intramuscular (i.m.) route. In the therapeutic MC38 tumor model, i.v. heterologous prime-boost vaccination enhances regression compared with ChAdOx1 alone. Remarkably, i.v. boosting with a ChAdOx1 vector encoding an irrelevant antigen also mediates tumor regression, which is dependent on type I IFN signaling. Single-cell RNA sequencing of the tumor myeloid compartment shows that i.v. ChAdOx1 reduces the frequency of immunosuppressive Chil3 monocytes and activates cross-presenting type 1 conventional dendritic cells (cDC1s). The dual effect of i.v. ChAdOx1 vaccination enhancing CD8 T cells and modulating the TME represents a translatable paradigm for enhancing anti-tumor immunity in humans. [Display omitted] • Intravenous heterologous prime boost with SNP-ChAdOx1 elicits potent CD8 T cell responses • Antigen-specific T cells are necessary but insufficient for therapeutic efficacy • Intravenous ChAdOx1 promotes tumor regression through type I IFN-dependent TME remodeling • Type I IFN reduces the frequency of immunosuppressive Chil3 monocytes in the TME Ramirez-Valdez et al. describe an intravenous heterologous prime-boost vaccination strategy that effectively promotes tumor regression by eliciting high-magnitude anti-tumor CD8 T cell responses and modulating the tumor microenvironment through type I IFN signaling. [ABSTRACT FROM AUTHOR]

Background Oxidative stress is closely linked to inflammation in neurodegenerative diseases. We aimed to investigate the expression of redox system genes in Multiple Sclerosis (MS) patients either exposed or not exposed to conventional treatments. Methods Forty-four MS patients were divided into three groups: newly diagnosed (Group 1), receiving interferon (Group 2) and receiving immunosuppressive drugs (Group 3). Also, 15 healthy controls were enrolled. The mRNA expression of TRX1 , TXNRD1 , TRX2 , TXNRD2 , TXNIP , and APEX1 genes in peripheral blood mononuclear cells (PBMCs) was assessed by relative quantitative real-time PCR. Also, serum level of Trx1 was measured by ELISA. Results Serum level of Trx1 in the newly diagnosed MS patients was significantly higher compared to the healthy controls ( P = 0.013). Likewise, TRX1 and APEX1 expressions were significantly higher in the newly diagnosed patients compared to controls ( P = 0.003 and P = 0.042), patients under interferon treatment ( P = 0.003 and P = 0.013), and patients received immunosuppressants ( P = 0.001 and P = 0.025). Furthermore, TXNIP expression in MS patients (either group 1, group 2, or group 3) was significantly lower than that in the control group ( P = 0.017, P = 0.002, and P = 0.022 respectively). The expression of TXNRD1 , TRX2 , and TXNRD2 did not show any significant difference between the control and the MS patient ( P > 0.05). Conclusions Our data showed that redox system elements are differentially expressed in newly diagnosed MS patients, or patients receiving either interferon or immunosuppressive treatments. However, much more studies are required to confirm our findings and clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

This paper investigates the transient stability issues that may occur when long underground cables are added to EHV transmission systems. Dynamic behaviour of generators and terminal voltages with respect to various disturbances like cable disconnection/connection and fault currents are studied. Simulations are performed for the 2020 model of the Dutch transmission grid. The effects of partial undergrounding in two case studies with the total transmission length of 280 km are investigated. This work proposes criteria for accurate sizing of cable shunt compensation for dynamic simulation purposes based on grid voltages, generator reactive powers and power exchange with neighbouring grids. Moreover, a comparison between the dynamic behaviour of system variables for three different shunt compensation arrangements including line-end compensation, line-end middle compensation, and cable-end compensation is performed. Finally, a specific switching sequence for line disconnection/connection to improve voltage profiles and generator behaviours is introduced. The simulations are performed in PSS ® E environment. [ABSTRACT FROM AUTHOR]