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Plasmodium ookinetes use an invasive apparatus to invade mosquito midguts, and tubulins are the major structural proteins of this apical complex. We examined the role of tubulins in malaria transmission to mosquitoes. Our results demonstrate that the rabbit polyclonal antibodies (pAb) against human α-tubulin significantly reduced the number of P. falciparum oocysts in Anopheles gambiae midguts, while rabbit pAb against human β-tubulin did not. Further studies showed that pAb, specifically against P. falciparum α-tubulin-1, also significantly limited P. falciparum transmission to mosquitoes. We also generated mouse monoclonal antibodies (mAb) using recombinant P. falciparum α-tubulin-1. Out of 16 mAb, two mAb, A3 and A16, blocked P. falciparum transmission with EC50 of 12 μg/ml and 2.8 μg/ml. The epitopes of A3 and A16 were determined to be a conformational and linear sequence of EAREDLAALEKDYEE, respectively. To understand the mechanism of the antibody-blocking activity, we studied the accessibility of live ookinete α-tubulin-1 to antibodies and its interaction with mosquito midgut proteins. Immunofluorescent assays showed that pAb could bind to the apical complex of live ookinetes. Moreover, both ELISA and pull-down assays demonstrated that insect cell-expressed mosquito midgut protein, fibrinogen-related protein 1 (FREP1), interacts with P. falciparum α-tubulin-1. Since ookinete invasion is directional, we conclude that the interaction between Anopheles FREP1 protein and Plasmodium α-tubulin-1 anchors and orients the ookinete invasive apparatus towards the midgut PM and promotes the efficient parasite infection in the mosquito.

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes. [ABSTRACT FROM AUTHOR]

Al–Mg–Si aluminum wires for overhead power transmission have extensive applications in industry and daily life. Herein, superior strength and electrical conductivity combinations in the aged cold‐drawn Al–Mg–Si–Ce–Cu wires fabricated by continuous casting and rolling are achieved. The cold‐drawn wires exhibit high strength and electrical conductivity combinations of 383 ± 2 MPa, 51.16 ± 0.23% International Annealed Copper Standard (IACS); 373 ± 3 MPa, 51.98 ± 0.25%; and 357 ± 3 MPa, 53.16 ± 0.11% IACS, respectively, when aged at 160, 170, or 180 °C for 24 h. Subgrain boundaries are introduced into alloys by continuous casting and rolling and cold drawing, causing significant lattice distortion within the grains and providing sites for the nucleation of precipitates. Moreover, high‐angle‐annular dark‐field scanning transmission electron microscopy and density functional theory results show that Ce atoms could enter the lattice of β" and replace the Si3 sites, which is energetically preferred. The underlying mechanisms for achieving superior strength–electrical conductivity combination are to introduce subgrain boundaries via continuous casting and rolling and cold drawing for promoting the transformation of solid solution atoms to finely dispersed precipitates, which significantly reduces the scattering of electrons and hence improves the electrical conductivity. This work provides a new strategy for designing high‐strength and high‐conductivity aluminum alloy wire conductors. [ABSTRACT FROM AUTHOR]

Introduction: Optimal occlusion of pulmonary vein (PV) is essential for atrial fibrillation (AF) cryoballoon ablation (CBA). The aim of the study was to investigate the performance of two different tools for the assessment of PV occlusion with a novel navigation system in CBA procedure. Methods: In consecutive patients with paroxysmal AF who underwent CBA procedure with the guidance of the novel 3‐dimentional mapping system, the baseline tool, injection tool and pulmonary venography were all employed to assess the degree of PV occlusion, and the corresponding cryoablation parameters were recorded. Results: In 23 patients (mean age 60.0 ± 13.9 years, 56.5% male), a total of 149 attempts of occlusion and 122 cryoablations in 92 PVs were performed. Using pulmonary venography as the gold standard, the overall sensitivity, specificity of the baseline tool was 96.7% (95% confidence interval [CI] 90.0%–99.1%), and 40.5% (95% CI 26.0%–56.7%), respectively, while the corresponding value of the injection tool was 69.6% (95% CI 59.7%–78.1%), and 100.0% (95% CI 90.6%–100.0%), respectively. Cryoablation with optimal occlusion showed lower nadir temperature (baseline tool: −44.3 ± 8.4°C vs. −35.1 ± 6.5°C, p <.001; injection tool: −46.7 ± 6.4°C vs. −38.3 ± 9.2°C, p <.001) and longer total thaw time (baseline tool: 53.3 ± 17.0 s vs. 38.2 ± 14.9 s, p =.003; injection tool: 58.5 ± 15.5 s vs. 41.7 ± 15.2 s, p <.001) compared with those without. Conclusions: Both tools were able to accurately assess the degree of PV occlusion and predict the acute cryoablation effect, with the baseline tool being more sensitive and the injection tool more specific. [ABSTRACT FROM AUTHOR]