Holocene Earthquake Cycles of an Active Tectonic Block Boundary Fault Zone: A Case Study in the Qilian–Haiyuan Fault Zone, Northeastern Tibet Plateau

Fault zones along active tectonic block boundaries are a significant source of devastating continental earthquakes. Strong earthquakes produce disruptions of sediment and induce characteristic sediments near the fault, which serve as valuable sedimentary evidence for identifying and dating of paleoearthquakes. In this study, we aimed to reconstruct the earthquake history of the Qilian–Haiyuan fault zone in the northeastern Tibetan Plateau during the Holocene. We reanalyzed forty-four trenches and used the sedimentary sequences, event indicators, and age constraints to determine the earthquake history. Our analysis revealed the paleoearthquakes of 6 subsidiary faults of the Qilian–Haiyuan fault zone with accurate event ages and rupture extents. Based on the spatial and temporal distributions of strong earthquakes since 10 ka, we identified five earthquake clusters around the central-eastern Qilian–Haiyuan fault zone including seven rupture cascades where the earthquakes migrated gradually from east to west. The existing seismic gap reveals that the latest migration may not yet be complete and suggests a high probability of M ≥ 7 earthquakes occurring on the Jinqianghe fault, Maomaoshan fault, and the central part of the Lenglongling faults. We concluded that, in order to better understand earthquake cycles and seismic hazards, it is important to consider a fault zone as a whole, including multiple faults and their interaction on the earthquake triggering between nearby faults

Neutralization of IL- 10 produced by B cells promotes protective immunity during persistent HCV infection in humanized mice

Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)- 10- producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV- induced B10 cells were enriched in CD19hi and CD1dhiCD5+ cell populations. HCV predominantly triggered the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL- 10 produced by B10 cells, mice were treated with pcCD19scFv- IL- 10R, which contains the genes coding the anti- CD19 single- chain variable fragment (CD19scFv) and the extracellular domain of IL- 10 receptor alpha chain (sIL- 10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8+ T- cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL- 10 may offer a novel strategy to enhance anti- HCV immunotherapy.HCV predominantly triggers the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. Neutralization of IL- 10 produced by B10 cells promotes anti- HCV immunity in a humanized murine model of persistent HCV infection. These results provide insight into a novel immunotherapy strategy for HCV treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/2/eji4736.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/1/eji4736_am.pd

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents

A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus strains. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative showed good potency against all four strains of Staphylococcus (MIC = 1.25 - 5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase structure to rationalize the observed antibacterial activity. Therefore, this series of GA derivatives have strong potential for the development of a new type of triterpenoid antibacterial agent

BRG1 Is Dispensable for Sertoli Cell Development and Functions in Mice

Sertoli cells are somatic supporting cells in spermatogenic niche and play critical roles in germ cell development, but it is yet to be understood how epigenetic modifiers regulate Sertoli cell development and contribution to spermatogenesis. BRG1 (Brahma related gene 1) is a catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex and participates in transcriptional regulation. The present study aimed to define the functions of BRG1 in mouse Sertoli cells during mouse spermatogenesis. We found that BRG1 protein was localized in the nuclei of both Sertoli cells and germ cells in seminiferous tubules. We further examined the requirement of BRG1 in Sertoli cell development using a Brg1 conditional knockout mouse model and two Amh-Cre mouse strains to specifically delete Brg1 gene from Sertoli cells. We found that the Amh-Cre mice from Jackson Laboratory had inefficient recombinase activities in Sertoli cells, while the other Amh-Cre strain from the European Mouse Mutant Archive achieved complete Brg1 deletion in Sertoli cells. Nevertheless, the conditional knockout of Brg1 from Sertoli cells by neither of Amh-Cre strains led to any detectable abnormalities in the development of either Sertoli cells or germ cells, suggesting that BRG1-SWI/SNF complex is dispensable to the functions of Sertoli cells in spermatogenesis

Blade Shape Optimization and Analysis of a Propeller for VTOL Based on an Inverse Method

With the rapid development of vertical takeoff and landing (VTOL) aircraft, the blade design of a propeller suitable for VTOL aircraft with a wide range of operating conditions has become a challenging and popular task. This paper proposes a multi-objective optimization framework for a VTOL propeller using an inverse design method at the cruising stage, which is developed from the Betz optimum theory and blade element momentum theory (BEMT). Different from passing studies, the maximum thrust-to-weight ratio at hover (MTWRH) is taken as one of the two objectives in this paper, which is closely related to the wind-resistance capability and maneuverability during takeoff and landing. The other objective is the energy consumption of the whole mission profile. A fixed pitch propeller (FPP) and a variable pitch propeller (VPP) are both optimized using the proposed framework for the Vahana A3 tilt-wing aircraft and validated by the computational fluid dynamics (CFD) method. The influences of the level flight energy ratio, hover disk loading and cruising speed toward the optimization result are analyzed, respectively. The results show that the MTWRH has a significant impact on the optimization result both for the FPP and VPP. A comparison between the two propeller forms validates the advantages of the VPP both in energy saving and takeoff maneuverability. The quantitative rules of this advantage with the level flight energy ratio are calculated to provide a reference for choosing the appropriate form. Overall, the methodology and general rules presented in this paper support the propeller optimization and form selection for VTOL aircraft

Aerodynamic Optimization and Analysis of Low Reynolds Number Propeller with Gurney Flap for Ultra-High-Altitude Unmanned Aerial Vehicle

Ultra-high-altitude unmanned aerial vehicles have created a high demand for the performance of propellers under low Reynolds numbers, while the efficiency of such propellers by the existing design framework has reached a bottleneck. This paper explores the possibility of extending the Gurney flap on low Reynolds number propellers to achieve efficiency breakthrough. An iterative optimization strategy for propellers with Gurney flaps is established, in which cross-sectional airfoils can be continuously optimized under updated Reynolds numbers and lift coefficients. A computational fluid dynamics (CFD) simulation based on the γ-Reθ model was used as an aerodynamic analysis method. Propellers with and without Gurney flaps were optimized successively. Optimal results were analyzed using the CFD method. Results showed that an optimal propeller with a Gurney flap can achieve an efficiency of 82.0% in cruising conditions, which is 1.8% higher than an optimal propeller without a Gurney flap. Compared with the latter, the consumed power of the optimal propeller with a Gurney flap can be reduced by 2.2% with the same advance speed. Furthermore, the variation of the improvement by the Gurney flap propeller, along with its Reynolds number, was studied. A wind tunnel test indicates that the performance of the propellers obtained by the CFD method are in good agreement with the test results

Effects of Cu(II) on the Adsorption Behaviors of Cr(III) and Cr(VI) onto Kaolin

The adsorption of Cr(III) or Cr(VI) in the absence and presence of Cu(II) onto kaolin was investigated under pH 2.0–7.0. Results indicated that the adsorption rate was not necessarily proportional to the adsorption capacity. The solutions’ pH values played a key role in kaolin zeta potential (ζ), especially the hydrolysis behavior and saturation index of heavy metal ions. In the presence of Cu(II), qmixCr(III) reached the maximum adsorption capacity of 0.73 mg·g−1 at pH 6.0, while the maximum adsorption capacity for the mixed Cr(VI) and Cu(II) system (qmixCr(VI)) was observed at pH 2.0 (0.38 mg·g−1). Comparing the adsorption behaviors and mechanisms, we found that kaolin prefers to adsorb hydrolyzed products of Cr(III) instead of Cr3+ ion, while adsorption sites of kaolin surface were occupied primarily by Cu(II) through surface complexation, leading to Cu(II) inhibited Cr(VI) adsorption. Moreover, Cr(III) and Cr(VI) removal efficiency had a positive correlation with distribution coefficient Kd. Cr(III) and Cr(VI) removal efficiency had a positive correlation with distribution coefficient Kd and that of adsorption affinities of Cr(III) or Cr(VI) on kaolin was found to be Kd Cr(III) < Kd Cr(III)-Cu(II) and Kd Cr(VI) > Kd Cr(VI)-Cu(II)

Telocytes reduce oxidative stress by downregulating DUOX2 expression in inflamed lungs of mice

Telocytes (TCs), a novel type of interstitial cells, have been found to participate in tissue protection and repair. In this study, we investigated the antioxidative effects of TCs in inflamed lungs of mice. Acute respiratory distress syndrome (ARDS) mice were used as models of inflamed lungs of mice. Gene sequencing was used to screen the differentially expressed miRNAs in TCs after lipopolysaccharide (LPS) stimulation. AntagomiR-146a-5p-pretreated TCs were first injected into mice, and antioxidant activity of TCs was estimated. TCs, RAW264.7 cells, and MLE-12 cells were collected for the detection of expressions of NOX1–4, DUOX1–2, SOD1–3, GPX1–2, CAT, Nrf2, miR-146a-5p, and miR-21a-3p after LPS stimulation. Silencing miRNAs were delivered to examine the involved signaling pathways. Oxidative stress was examined by measuring malondialdehyde (MDA) levels. We found that microRNA-146a-5p and microRNA-21a-3p were upregulated in TCs after LPS stimulation. ARDS mice that were preinfused with TCs had lower lung tissue injury scores, lung wet-dry ratios, white blood cell counts in alveolar lavage fluid and lower MDA concentrations in lung tissue. However, in antagomiR-146a-5p-pretreated ARDS mice, the infusion of TCs caused no corresponding changes. After LPS stimulation, DUOX2 and MDA concentrations were downregulated in TCs, while DUOX2 was restored by antagomiR-146a-5p in TCs. Dual-luciferase reporter assay confirmed that CREB1 was downregulated by miR-146a-5p, while DUOX2 was downregulated by CREB1, which was confirmed by treating TCs with a specific CREB1 inhibitor. This study demonstrates that LPS stimulation upregulates miR-146a-5p in TCs, which downregulates the CREB1/DUOX2 pathway, resulting in a decrease in oxidative stress in cultured TCs. TCs reduce LPS-induced oxidative stress by decreasing DUOX2 in inflamed lungs of mice

Reduction in Peripheral CD19+CD24hCD27+ B Cell Frequency Predicts Favourable Clinical Course in XELOX-Treated Patients with Advanced Gastric Cancer

Background: Accumulating evidence suggests that regulatory B cells (Bregs) play an important role in modulating the immune response to tumours. Our previous study indicated that a small percentage of peripheral CD19+CD24hCD27+ Breg cells slowed gastric cancer progression in XELOX-treated patients. Here, we further investigated the relationship between dynamic changes in circulating Breg cells and the clinical course in XELOX-treated gastric cancer patients. Methods: A total of 52 patients with advanced gastric cancer were enrolled in this study. The frequencies of CD19+CD24hCD27+ cells in peripheral blood were tested before (as a baseline) and 9 weeks after administration of oxaliplatin and capecitabine (XELOX). The primary endpoint of the study was progression-free survival time (PFS) of the patients. The overall survival (OS) and adverse events of chemotherapy were also recorded. Results: The median PFS of patients was 6 months (95% CI, 5.27-6.73) with effective rate of 46.2%. The percentage of CD19+CD24hCD27+ cells in lymphocytes ranged from 0.007% to 1.94%, with a median value of 0.45%. The median percentage of CD19+CD24hCD27+ lymphocytes was 0.59% (0.01%-6.02%) 9 weeks after treatment. There were no significant differences for this index. However, the patients with decreased Breg frequencies after XELOX treatment had a longer PFS time (7.0 months vs. 5.0 months, p=0.01) than those with increased Breg frequencies. Conclusion: Patients with downtrend of CD19+CD24hCD27+ B lymphocytes during early stages of chemotherapy relative to their initial values had longer PFS times, and this could be used to predict the efficacy of chemotherapy and help physicians adjust treatments accordingly