Formulation improvement of a concentrated enzyme detergent for high-speed rail trains through life cycle assessment methodology.

High-speed rail has been operating in more than 25 countries (mainly in Asia, Europe and North America), and has become an important part of global economic development. However, the cleaning and maintenance of high-speed rail is a comprehensive task, which may easily cause environmental pollution. This study aims to analyze and improve the sustainability of the formulation and production process of a concentrated complex enzyme detergent used as the maintenance agent for high-speed trains via the life cycle assessment (LCA) method. The eFootprint software system with built-in China, European and Swiss Ecoinvent databases was used to establish the LCA model with the system boundary being from cradle to gate. The LCA model showed that the production of 1 kg of concentrated detergent generates the global warming potential of 2.53 kg CO2 eq, and other environmental emissions including acidification potential of 0.01 kg SO2 eq, eutrophication potential of 3.76E-03 kg PO43-eq, inhalable inorganic matter of 3.17E-03 kg PM2.5 eq, ozone depletion potential of 5.3E-06 kg CFC-11 eq, photochemical ozone formation potential of 3.44E-03 kg NMVOC eq, primary energy demand of 3.17 MJ, abiotic depletion potential of 4.97E-6 kg antimony eq, and water use of 0.84 kg. LCA results are not strongly dependent to the assumptions of the research, and the uncertainties of LCA results are between 8 and 16%, which is mainly due to the regional differences in technology sources, the year of technical data collection, and the representativeness of technology collection companies. Carbon footprint analysis showed that the production processes of enzyme stabilizer (glycerol) and surfactants contributed the most, while changes in power consumption during production and transportation distance of raw materials had limited effect on total carbon emissions. Therefore, the formulation of the concentrated complex enzymatic detergent was improved based on the LCA results. The new formulations with less enzyme stabilizer showed similar detergency to the original formulation. The new formulations could reduce carbon emissions by 5,500-9,200 tons per year and save between $4.4 and $7.4 million in annual production of 10,000 tons. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-023-03122-2.

Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus.

How the fetus escapes rejection by the maternal immune system remains one of the major unsolved questions in transplantation immunology. Using a system to visualize both CD4+ and CD8+ T cell responses during pregnancy in mice, we find that maternal T cells become aware of the fetal allograft exclusively through "indirect" antigen presentation, meaning that T cell engagement requires the uptake and processing of fetal/placental antigen by maternal APCs. This reliance on a relatively minor allorecognition pathway removes a major threat to fetal survival, since it avoids engaging the large number of T cells that typically drive acute transplant rejection through their ability to directly interact with foreign MHC molecules. Furthermore, CD8+ T cells that indirectly recognize fetal/placental antigen undergo clonal deletion without priming for cytotoxic effector function and cannot induce antigen-specific fetal demise even when artificially activated. Antigen presentation commenced only at mid-gestation, in association with the endovascular invasion of placental trophoblasts and the hematogenous release of placental debris. Our results suggest that limited pathways of antigen presentation, in conjunction with tandem mechanisms of immune evasion, contribute to the unique immunological status of the fetus. The pronounced degree of T cell ignorance of the fetus also has implications for the pathophysiology of immune-mediated early pregnancy loss.

Ovarian insufficiency and early pregnancy loss induced by activation of the innate immune system.

We describe a murine model of early pregnancy failure induced by systemic activation of the CD40 immune costimulatory pathway. Although fetal loss involved an NK cell intermediate, it was not due to lymphocyte-mediated destruction of the fetus and placenta. Rather, pregnancy failure resulted from impaired progesterone synthesis by the corpus luteum of the ovary, an endocrine defect in turn associated with ovarian resistance to the gonadotropic effects of prolactin. Pregnancy failure also required the proinflammatory cytokine TNF-alpha and correlated with the luteal induction of the prolactin receptor signaling inhibitors suppressor of cytokine signaling 1 (Socs1) and Socs3. Such links between immune activation and reproductive endocrine dysfunction may be relevant to pregnancy loss and other clinical disorders of reproduction.

Interleukin-21 is required for the development of type 1 diabetes in NOD mice.

OBJECTIVE: Interleukin (IL)-21 is a type 1 cytokine that has been implicated in the pathogenesis of type 1 diabetes via the unique biology of the nonobese diabetic (NOD) mouse strain. The aim of this study was to investigate a causal role for IL-21 in type 1 diabetes. RESEARCH DESIGN AND METHODS: We generated IL-21R-deficient NOD mice and C57Bl/6 mice expressing IL-21 in pancreatic beta-cells, allowing the determination of the role of insufficient and excessive IL-21 signaling in type 1 diabetes. RESULTS: Deficiency in IL-21R expression renders NOD mice resistant to insulitis, production of insulin autoantibodies, and onset of type 1 diabetes. The lymphoid compartment in IL-21R-/- NOD is normal and does not contain an increased regulatory T-cell fraction or diminished effector cytokine responses. However, we observed a clear defect in autoreactive effector T-cells in IL-21R-/- NOD by transfer experiments. Conversely, overexpression of IL-21 in pancreatic beta-cells induced inflammatory cytokine and chemokines, including IL-17A, IL17F, IFN-gamma, monocyte chemoattractant protein (MCP)-1, MCP-2, and interferon-inducible protein-10 in the pancreas. The ensuing leukocytic infiltration in the islets resulted in destruction of beta-cells and spontaneous type 1 diabetes in the normally diabetes-resistant C57Bl/6 and NOD x C57Bl/6 backgrounds. CONCLUSIONS: This work provides demonstration of the essential prodiabetogenic activities of IL-21 on diverse genetic backgrounds (NOD and C57BL/6) and indicates that IL-21 blockade could be a promising strategy for interventions in human type 1 diabetes.

Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells.

We previously described a mouse model of ulcerative colitis linked to T-bet deficiency in the innate immune system. Here, we report that the majority of T-bet(-/-)RAG2(-/-) ulcerative colitis (TRUC) mice spontaneously progress to colonic dysplasia and rectal adenocarcinoma solely as a consequence of MyD88-independent intestinal inflammation. Dendritic cells (DCs) are necessary cellular effectors for a proinflammatory program that is carcinogenic. Whereas these malignancies arise in the setting of a complex inflammatory environment, restoration of T-bet selectively in DCs was sufficient to reduce colonic inflammation and prevent the development of neoplasia. TRUC colitis-associated colorectal cancer resembles the human disease and provides ample opportunity to probe how inflammation drives colorectal cancer development and to test preventative and therapeutic strategies preclinically.