Multiple Signaling Pathways Are Involved in the Interleukine-4 Regulated Expression of DC-SIGN in THP-1 Cell Line

Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signaling pathways involved in IL-4-regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis of cis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site

Immune interference in effectiveness of influenza and COVID-19 vaccination

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic

CaS: A key medium for C-O-S-Ca cycles in Earth

Oldhamite (CaS) is a rare mineral, which is only observed naturally in enstatite meteorites.No occurrence of CaS has been documented from other groups of meteorites and terrestrial samples. However, in experiments at 1.5 GPa/1510 K and 0.5 GPa/1320 K, when the lgfo2 is lower than -10.57 (FMQ-0.52), CaS was produced in this study by a two-melt mechanism involving the reaction between molten pyrrhotite-pentlandite-bearing orthopyroxenite and molten CaCO3. CaS can be easily oxidized to form CaSO4 or hydrolyzed to produce calcium hydroxide, which may explain why it has never been found in geological samples from Earth. We speculate that part of the anhydrite and gypsum in black smokers along mid-ocean ridges are related to the oxidation or hydrolysis of CaS in the underlying mantle. CaS can be produced when the Siberian mantle plume intruded into the lithosphere.Comment: The third versio

Dissecting the Contribution of Individual Receptor Subunits to the Enhancement of N-methyl-d-Aspartate Currents by Dopamine D1 Receptor Activation in Striatum

Dopamine, via activation of D1 receptors, enhances N-methyl-d-aspartate (NMDA) receptor-mediated responses in striatal medium-sized spiny neurons. However, the role of specific NMDA receptor subunits in this enhancement remains unknown. Here we used genetic and pharmacological tools to dissect the contribution of NR1 and NR2A/B subunits to NMDA responses and their modulation by dopamine receptors. We demonstrate that D1 enhancement of NMDA responses does not occur or is significantly reduced in mice with genetic knock-down of NR1 subunits, indicating a critical role of these subunits. Interestingly, spontaneous and evoked α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptor-mediated responses were significantly enhanced in NR1 knock-down animals, probably as a compensatory mechanism for the marked reduction in NMDA receptor function. The NMDA receptor subunits NR2A and NR2B played differential roles in D1 modulation. Whereas genetic deletion or pharmacological blockade of NR2A subunits enhanced D1 potentiation of NMDA responses, blockade of NR2B subunits reduced this potentiation, suggesting that these regulatory subunits of the NMDA receptor counterbalance their respective functions. In addition, using D1 and D2 receptor EGFP-expressing mice, we demonstrate that NR2A subunits contribute more to NMDA responses in D1-MSSNs, whereas NR2B subunits contribute more to NMDA responses in D2 cells. The differential contribution of discrete receptor subunits to NMDA responses and dopamine modulation in the striatum has important implications for synaptic plasticity and selective neuronal vulnerability in disease states

Diet and lifestyle interventions in postpartum women in China: study design and rationale of a multicenter randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>"Doing the month", or "sitting month", is a traditional practice for postpartum women in China and other Asian countries, which includes some taboos against well-accepted healthy diet and lifestyles in general population. Previous studies have shown this practice may be associated with higher prevalence of postpartum problems. The current multicenter randomized controlled trial (RCT) aims to evaluate outcomes of diet and lifestyle interventions in Chinese postpartum women.</p> <p>Methods/Design</p> <p>The current multicenter RCT will be conducted in three representative areas in China, Shandong province, Hubei province and Guangdong province, which locate in northern, central and southern parts of China, respectively. Women who attend routine pregnancy diagnosis in hospitals or maternal healthcare centers will be invited to take part in this study. At least 800 women who meet our eligibility criteria will be recruited and randomly assigned to the intervention group (n > = 400) and the control group (n > = 400). A three-dimension comprehensive intervention strategy, which incorporates intervention measures simultaneously to individual postpartum woman, their family members and community environment, will be utilized to maximize the effectiveness of intervention. Regular visiting and follow-up will be done in both group; nutrition and health-related measurements will be assessed both before and after the intervention.</p> <p>Discussion</p> <p>To our knowledge, this current study is the first and largest multicenter RCT which focus on the effectiveness of diet and lifestyle intervention on reducing the incidence rate of postpartum diseases and improving health status in postpartum women. We hypothesize that the intervention will reduce the incidence rates of postpartum diseases and improve nutrition and health status due to a balanced diet and reasonable lifestyle in comparison with the control condition. If so, the results of our study will provide especially important evidence for changes in both the concept and action of traditional postpartum practice in China.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID NCT01039051.</p

Sulfur isotopic evolution of Phanerozoic and Ediacaran seawater sulfate

Dynamics of &sigma34S and &sigma33S of oceanic sulfate and sedimentary pyrite over geologic time has been used to understand and extract information about the marine sulfur cycle. My Ph.D project uses this approach to study the evolution of the marine sulfur cycle and focuses on: 1)Providing temporal &sigma34S and &sigma33S records for Phanerozoic and Ediacaran seawater sulfate based on the analysis of carbonate associated sulfate 2) Reinterpreting previously documented variations of sulfur isotope fractionation using new measurements of &sigma33S of oceanic sulfate. The sulfur isotope fractionation between sulfate and pyrite appears to have varied widely, between 25 / to 40 / over the course of Phanerozoic. For the earlier part of Phanerozoic, the values of sulfur isotope fractionation are approximately 35 /. The fractionation then decreases to 25 / during the Carboniferous Period. Following this, the sulfur isotope fractionations progressively increase, reaching approximately 40 / during the Cenozoic Period. 3) Evaluating the connection between sulfate concentration, sulfide re-oxidation and sulfate exchange between water column and marine sediment systems using steady state and also non steady state models. The model results and the data presented here suggest the sulfur cycle in the Ediacaran Oman basin evolved from one that was similar to the global sulfur cycle to a sulfur cycle that was disconnected or partially was disconnected from the open ocean sulfur cycle. It also implies that the sulfate levels drop at this transition due to weakening of vertical bioturbation or weakening of other physical processes that involve in mixing of sulfate in pore water and overlying sulfate in marine settings. The significance of these three directions is the new information that they provide about the evolution of the sulfur cycle. It is relevant to understanding the environmental changes and their connections to sulfur ecosystem evolution for the geological time interval extending from present until latest Precambrian