Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); however, the biological significance of this cleavage is elusive. Taking advantage of the recent identification of a GPR56 ligand and the presence of BFPP-associated mutations, we investigated the molecular mechanism of GPR56 signaling. We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation. Furthermore, one of the BFPP-associated mutations, L640R, does not affect collagen III-induced lipid raft association of GPR56. Instead, it specifically abolishes collagen III-mediated RhoA activation. Together, these findings reveal a novel signaling mechanism that may apply to other members of the adhesion GPCR family

Mesoporous High‐Surface‐Area Copper–Tin Mixed‐Oxide Nanorods: Remarkable for Carbon Monoxide Oxidation

Mesoporous, high‐surface‐area Cu–Sn mixed‐oxide nanorods were fabricated for the first time by nanocasting with the use of mesoporous KIT‐6 silica as the hard template. The Cu–Sn nanorods are significantly more active than 1 % Pd/SnO2 for the oxidation of CO and possesses long‐term durability and potent water resistance; they thus have the potential to replace noble metal catalysts for emission‐control processes.In rod we trust: Mesoporous, high‐surface‐area Cu–Sn nanorods are successfully fabricated for the first time by nanocasting with the use of KIT‐6 silica as the hard template; these nanomaterials are significantly more active than 1 % Pd/SnO2 for the oxidation of CO, and furthermore, they have the potential to replace noble metal catalysts for emission control.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/1/cctc201600221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/2/cctc201600221-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137536/3/cctc201600221_am.pd

Ecological vulnerability assessment based on remote sensing ecological index (RSEI): A case of Zhongxian County, Chongqing

The ecological vulnerability evaluation index was established through Normalized Difference Vegetation Index (NDVI), Wetness (WET), Normalized Difference Build-up and Soil Index (NDBSI) and Land Surface Temperature (LST) indicators, comprehensively evaluate the ecological vulnerability of Zhongxian County of Chongqing in 2002, 2009, and 2016 by Principal Components Analysis (PCA), and analyze its spatio-temporal evolution. The vulnerability areas of five levels were calculated respectively, and the overall index of ecological vulnerability was also calculated. The index of remote sensing ecological index (RSEI) and Normalized Difference Vegetation Index decreased first and then increased; the Wetness index showed an upward trend; the Normalized Difference Build-up and Soil Index index increased first and then decreased; and the Land Surface Temperature index decreased. The ecological vulnerability body index (EVBI) shows a downward trend, and the incremental changes are mainly concentrated in the negligible vulnerability areas and light vulnerability area, while the medium vulnerability, strong vulnerability and extreme vulnerability area generally show a downward trend. Furthermore, the new increment of ecological vulnerability grade area concentrates on negligible vulnerability area and light vulnerability area from 2002 to 2016. In general, the ecological vulnerability gradually shifts to low vulnerability, and the ecological environment tends to develop healthily

Efficacy and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage: a systematic review and meta-analysis

Background: Despite some progress has been made in the pathogenesis and treatment of threatened miscarriage (TM), conventional treatment remains suboptimal. Thus, complementary medicine gradually become a new treatment option for treating threatened miscarriage. Gushen Antai Pills (GAP), a classic prescription of Traditional Chinese medicine (TCM), has became a popular complementary therapy to conventional western medicine (dydrogesterone) in treating threatened miscarriage in recent years. However, a systematic summary and analysis for its therapeutic effects is lacking. This meta-analysis aimed to systematically evaluate the effectiveness and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage.Methods: A systematic search across seven electronic databases was conducted from inception to 17 September 2022. Studies were included if they were randomized controlled trials (RCTs) evaluating the effect of integrating Gushen Antai Pills and dydrogesterone in patients with threatened miscarriage, and reported the outcomes of interest. All statistical analyses were conducted using the Revman5.3 and Stata 13 software. The GRADE system was used to evaluate the quality of evidence.Results: Ten eligible randomized controlled trials involving 950 participants were contained in this meta-analysis. The pooled analysis showed that Gushen Antai Pills combined with dydrogesterone can significantly reduce the incidence of early pregnancy loss (RR: 0.29; 95% CI: 0.19–0.42; p < 0.00001) and alleviate clinical symptoms (RR: 1.39; 95% CI: 1.22–1.59; p < 0.00001), compared with treatment of dydrogesterone alone. Also, meta-analysis indicated that integrating Gushen Antai Pills and dydrogesterone is more effective than using dydrogesterone alone in improving hormone levels (serum levels of progesterone, β-HCG and estradiol) for women with threatened miscarriage (all p < 0.00001). Meanwhile, the combined effects with significant heterogeneity also showed favorable consistency in the sensitivity analyses, indicating a good stability of present results. Moreover, no significant differences between Gushen Antai Pills combined with dydrogesterone and control group on adverse events was identified. The overall GRADE qualities were low to moderate.Conclusion: The overall available evidence suggested that Gushen Antai Pills combined with dydrogesterone had significant effects in improving pregnancy success rate, clinical symptoms and hormone levels for women with threatened miscarriage, with considerable safety and reliability. However, due to the partial heterogeneity, suboptimal quality and high risk of bias of some included studies, further rigorously designed randomized controlled trials are required.Systematic Review Registration: identifier https://INPLASY2022120035, https://inplasy.com/inplasy-2022-12-0035/

Immunomodulatory Effects of Cinobufagin on Murine Lymphocytes and Macrophages

Cinobufagin (CBG), a major bioactive component of the traditional Chinese medicine ChanSu, has been reported to have potent pharmacological activity. In this study, we aimed to elucidate the effects of CBG on the activity of immune cells in mice. Peritoneal macrophages and splenocytes from mice were prepared and cultured in RPMI1640 supplemented with 10% fetal bovine serum. Concanavalin (ConA), lipopolysaccharide (LPS), and CBG (0.0125, 0.05, 0.15, or 0.25 μg/mL) were added to the culture medium, and the phagocytic activity of macrophages was detected by MTT assays. Additionally, lymphocyte secretion of interleukin- (IL-)2 and IL-10 was detected by enzyme-linked immunosorbent assay, and the cell cycle distribution and cell surface markers were detected by flow cytometry. Our results demonstrated that CBG promoted lymphocyte proliferation; this effect was suppressed by combined treatment with ConA or LPS. Moreover, CBG also significantly improved the CD4+/CD8+ ratio in spleen lymphocytes and increased the percentage of spleen lymphocytes in the S phase. Finally, we found that CBG enhanced the secretion of IL-2 and IL-10 and increased the phagocytosis ability of macrophages. In summary, CBG could enhance activity of immune cells

Disease-Associated Mutations Prevent GPR56-Collagen III Interaction

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown

Proteomics Reveals Novel Drosophila Seminal Fluid Proteins Transferred at Mating

Across diverse taxa, seminal fluid proteins (Sfps) transferred at mating affect the reproductive success of both sexes. Such reproductive proteins often evolve under positive selection between species; because of this rapid divergence, Sfps are hypothesized to play a role in speciation by contributing to reproductive isolation between populations. In Drosophila, individual Sfps have been characterized and are known to alter male sperm competitive ability and female post-mating behavior, but a proteomic-scale view of the transferred Sfps has been missing. Here we describe a novel proteomic method that uses whole-organism isotopic labeling to detect transferred Sfps in mated female D. melanogaster. We identified 63 proteins, which were previously unknown to function in reproduction, and confirmed the transfer of dozens of predicted Sfps. Relative quantification of protein abundance revealed that several of these novel Sfps are abundant in seminal fluid. Positive selection and tandem gene duplication are the prevailing forces of Sfp evolution, and comparative proteomics with additional species revealed lineage-specific changes in seminal fluid content. We also report a proteomic-based gene discovery method that uncovered 19 previously unannotated genes in D. melanogaster. Our results demonstrate an experimental method to identify transferred proteins in any system that is amenable to isotopic labeling, and they underscore the power of combining proteomic and evolutionary analyses to shed light on the complex process of Drosophila reproduction

Evaluation of the effect of pressure and heat transfer on the efficiency of a batch fuel reactor, using Iron-based Oxygen Carrier with a CFD model

19 figures, 4 tables.Coupling a Chemical Looping Combustor fed with biofuels with a turbo expander is a promising Negative Emissions Technology (NET) to realize climate neutral targets in China and Europe. This is also an example of Bioenergy with Carbon Capture and Storage (BECCS) technology. To realize it, we need a Pressurized Chemical Looping Combustion process (PCLC). In this work, a Eulerian-Lagrangian hybrid model is developed in Barracuda-VRTM software, incorporating chemical reactions to predict the performance of a Fuel Reactor using Fe2O3 as oxygen carrier and syngas as fuel, under different pressures, ranging from 1 bar to 20 bars. The model predicted the conversion efficiency of syngas reduction using an iron-based oxygen carrier (Fe2O3/Al2O3). The results show, that the increase in pressure promotes the conversion of CO and inhibits the conversion of H2. When the two gases are considered together, the increase in pressure promotes the reaction between syngas and Fe2O3 and reduces the demand for Fe2O3 oxygen carrier per unit of syngas Lower Heating Value and so also the inventory of the reactor. Increasing temperatures promotes both the reaction of H2 and CO with Fe2O3. Dealing with CO conversion, this is more affected by pressure changes and temperature changes than H2. This represents important information for Fuel Reactor design, scale up and optimization. Further validation is neded in batch and continuous pressurised plants.This work has been funded by the GTCLC-NEG project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 101018756.Peer reviewe