SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity

Background The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on immunocompromised CAR T-cell therapy recipients and kidney transplant recipients (KTRs) has not yet been established.Case presentation In this report, we compare two patients with severe COVID-19 pneumonia in either the humoral or cell-mediated immunodeficient states. The first patient was a man in his early 30s who was diagnosed with refractory multiple myeloma. He received fully humanized, anti-B-cell maturation antigen, CAR T-cell therapy before 4 months and achieved strict complete remission. He was infected with SARS-CoV-2 starting on January 26, 2019 and gradually progressed to severe pneumonia. Throughout the clinical progression of the disease, SARS-CoV-2 could not be cleared due to his humoral immunodeficient state. During this period of his severe COVID-19 pneumonia, elevated cytotoxic T-cells were observed in this patient’s peripheral blood while elevated plasma levels of interleukin (IL)-2R, IL-6, tumor necrosis factor α, and ferritin were observed in his cytokine profiles. This patient eventually progressed into acute respiratory distress syndrome and recieved non-invasive ventilatory support. He failed to generate specific SARS-CoV-2 antibodies and died of respiratory failure on day 33 (d33). The second patient was a 52-year-old kidney transplant recipient (KTR) who took ciclosporin after renal transplantation for more than 7 years. He confirmed SARS-CoV-2 infection on January 20, 2019 and gradually progressed into severe pneumonia on d16 with a slightly elevated B-cell percentage and normal T-lymphocyte subsets. Viral clearance occurred together with the generation of specific anti-immunoglobulin G-SARS-CoV-2 antibodies after 2 weeks of treatment. He was symptom-free and discharged from the hospital on d42.Conclusion We report a CAR T-cell therapy recipient diagnosed with COVID-19 for the first time. His virus clearance failure and life-threating cytokine storm during SARS-CoV-2 infection suggested that any decision to proceed CAR T-cell therapy during COVID-19 pandemics will require extensive discussion of potential risks and benefits. Immunosuppressant treatment based on ciclosporin could be relatively safe for KTRs diagnosed with COVID-19.Trial registration number ChiCTR-OPN-1800018137

Performance analysis and optimization of multi-stage combined thermoelectric generators

A numerical model of multi-stage combined thermoelectric generators is established based on non-equilibrium thermodynamics. Taking a 5-stage thermoelectric generator for example, the output characteristics are analyzed. With the power and efficiency as the goal, the thermoelectric elements configuration and electrical current are optimized synchronously. The results show that when the temperature difference and the Seebeck coefficient are small, same number of thermoelectric elements in each stage results in the maximal power output; when the temperature difference or the Seebeck coefficient is large, the optimal configuration is that the numbers of thermoelectric elements increase with the same difference from the high temperature stage to the low temperature stage.Papers presented at the 13th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Portoroz, Slovenia on 17-19 July 2017 .International centre for heat and mass transfer.American society of thermal and fluids engineers

Thermal-Hydraulic Characteristics of Carbon Dioxide in Printed Circuit Heat Exchangers with Staggered Airfoil Fins

Airfoil fin printed circuit heat exchangers (PCHEs) have broad application prospects in the naval, aerospace, electric power, and petrochemical industries. The channel structure is a critical factor affecting their thermal-hydraulic characteristics. In this study, a novel PCHE channel structure with staggered NACA 0025 airfoil-shaped fins was proposed; accordingly, the thermal-hydraulic characteristics of the novel channel structure using carbon dioxide as the working fluid at different fin heights under different operating conditions (trans-, near-, and far-critical) were investigated. The results indicated that the thermal-hydraulic performance of the PCHE under the trans-critical operating condition was better than that under the near-critical and far-critical operating conditions. Compared with conventional airfoil fin channels, the novel airfoil fin channel attained comparable comprehensive performance while reducing the fin volume by 50%, thus achieving a more lightweight PCHE design. The comprehensive performance of the PCHE was the poorest when the fin height was slightly below the channel height, which should be avoided during the design of airfoil fin PCHEs. The results provide theoretical support for the design and optimization of airfoil fin PCHEs

Identification of two new species of Meliolinites associated with Lauraceae leaves from the middle Miocene of Fujian, China

Several studies have investigated both the paleoclimate and the well-preserved fossil remains from the middle Miocene found in China\u27s Fujian Province. This study describes two new species of Meliolinites, including their fungal hyphae, reproductive structures, and spores. The distribution of modern Meliolaceae indicates that they live in warm, humid, subtropical to tropical climates. Moreover, the fossil leaves and the epiphyllous fungal remains, indicate the prevalence of a warm, humid, subtropical to tropical climate in this area during the middle Miocene. In addition, it was observed that the surrounding cells of the fungi found on the uninfected host leaves were normal, whereas the infected host leaves themselves were abnormally dim. These features are a reflection of self-protection, and it can, therefore, be inferred that the host leaves were alive when they were infected. The present study used fossil angiosperm leaves with cuticles obtained from the Fotan sediments from Fujian to investigate not only the taxonomy of the fossils but also to interpret the paleoclimate and paleoecology

NLP2-NR Module Associated NO Is Involved in Regulating Seed Germination in Rice under Salt Stress

Salt stress has the most severe impact on plant growth and development, including seed germination. However, little is known about the mechanism of NR (nitrate reductase)-associated nitric oxide (NO) regulates salt tolerance during seed germination in rice. Herein, we shown that inhibition of seed germination by salt stress was significantly impaired by sodium nitroferricyanide (SNP), a NO donor. Then a triple mutant, nr1/nr2/nr3, was generated. Results shown that germination of triple mutants were delayed and were much more sensitive to salt stress than WT plant, which can be rescued by application of SNP. qPCR analysis revealed that expressions of abscisic acid (ABA) catabolism gene, OsABA8ox1, was suppressed in triple mutants under salt stress, resulting in an elevated ABA content. Similar to SNP, application of nitrate also rescued seed germination under salt stress, which, however, was blocked in the triple mutants. Further study revealed that a nitrate responsive transcript factor, OsNLP2, was induced by salt stress, which thus up-regulates the expression of OsNRs and NR activity, resulting in promoted salt tolerance during seed germination. In addition, nitrate-mediated salt tolerance was impaired in mutant of aba8ox1, a target gene for NLP2. Transient trans-activation assays further revealed NLP2 can significantly activate the expression of OsABA8ox1 and OsNR1, suggesting that NLP2 activates expression of ABA catabolism gene directly or indirectly via NR-associated NO. Taken together, our results demonstrate that NLP2-NR associated NO was involved in salt response by increasing ABA catabolism during seed germination and highlight the importance of NO for stress tolerance of plants