The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed of the PB1, PB2, and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nuclei of infected cells. In this study, we newly identified host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with the bPB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substratebinding domain and not on its typical J domain, while the J domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner. IMPORTANCEThe interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaptation. In this study, we newly identified a host protein, DnaJA1/Hsp40, that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nuclei of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into the nucleus along with the nuclear import of the PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, which is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of the Hsp40s that is specifically involved in regulating influenza virus RNA polymerase. Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs.

Non-collinear antiferromagnetic materials have received dramatically increasing attention in the field of spintronics as their exotic topological features such as the Berry-curvature-induced anomalous Hall effect and possible magnetic Weyl states could be utilized in future topological antiferromagnetic spintronic devices. In this work, we report the successful integration of the antiferromagnetic metal Mn3Sn thin films onto ferroelectric oxide PMN-PT. By optimizing growth, we realized the large anomalous Hall effect with small switching magnetic fields of several tens mT fully comparable to those of bulk Mn3Sn single crystals, anisotropic magnetoresistance and negative parallel magnetoresistance in Mn3Sn thin films with antiferromagnetic order, which are similar to the signatures of the Weyl state in bulkMn3Sn single crystals. More importantly, we found that the anomalous Hall effect in antiferromagnetic Mn3Sn thin films can be manipulated by electric fields applied onto the ferroelectric materials, thus demonstrating the feasibility of Mn3Sn-based topological spintronic devices operated in an ultralow power manner. Experimental methodsMn3Sn films were grown on (001)-oriented MgO, 0.7PbMg1/3Nb2/3O3-0.3PbTiO3 (PMN-PT), 100-nm-thick LaAlO3-buffered PMN-PT substrates from a polycrstalline Mn3Sn target by a d.c. sputtering system with a base pressure of 7.5×10 -9 Torr. The growth temperature was 150 ˚C. The sputtering power and the Ar pressure during deposition were 60 W and 3 mTorr, respectively. The growth rate was ~0.28 Å/s as determined by transmission electron microscopy measurements. Co90Fe10 (CoFe) thin films were grown by the d.c. sputtering system as well. The sputtering power and the Ar pressure were 90 W and 3 mTorr, respectively. The growth rate was ~0.11 Å/s. Pt thin films were sputtered by 30 W at an Ar pressure of 3 mTorr. Its growth rate was 0.5 Å/s. The 100-nm-thick LaAlO3 buffer layers on PMN-PT substrates were fabricated by pulsed laser deposition with a laser fluence of ~1.6 J/cm 2 , an oxygen pressure of 10 -2 Torr and a repetition rate of 10 Hz at 800 ˚C. The focused laser spot size was 1×3 mm 2 and the target-substrate distance was 60 mm. The deposition rate of LaAlO3 is ~0.11 Å/pulse. A Quantum Design VersaLab system was used for conducting electrical and magnetic measurements. The measuring current was 1 mA supplied from a Keithley 2400 sourcemeter.A Keithley 2182A nanovolt meter was used to collect voltage signals for both longitudinal and transverse resistance measurements. The gate electric field was supplied by another Keithley 2400 sourcemeter. Results and discussionFirstly, by varying the growth temperature of Mn3Sn thin films onto (001)-oriented MgO single-crystal substrates from room temperature to 750 ˚C, we identified that the optimal growth temperature for achieving the most remarkable AHE and the lowest magnetic field for switching the anomalous Hall resistance is 150 ˚C. As shown in Fig. 1a, a 50-nm-thick Mn3Sn/MgO heterostructure fabricated at 150 ˚C exhibit a rather sharp inte...

Background: Injectable hyaluronic acid fillers have been widely applied in the clinical treatment of facial wrinkles. However, further information and clinical evidence concerning dermal changes and hyaluronic acid filler longevity after injection and diffusion pattern are limited. Methods: The authors evaluated the longevity and diffusion pattern of two hyaluronic acid fillers generated by different cross-linking technologies used in the treatment of nasolabial folds using high-frequency ultrasound. Forty-one subjects were treated with Restylane 2 and the remaining 41 were treated with Dermalax DEEP. Wrinkle severity rating scale score and high-frequency ultrasound evaluation of nasolabial folds were performed before and after the injection of hyaluronic acid filler. The ultrasound images were acquired and analyzed to determine dermal thickness and the shape and distribution of hyaluronic acid filler. Results: At 2 and 24 weeks from baseline, increased dermal thickness induced by hyaluronic acid filler treatment was not significantly different between groups. At 48 weeks after injection, increased dermal thicknesses of the Restylane 2 group (0.14 ± 0.12 mm) were much lower than those of the Dermalax DEEP group (0.20 ± 0.13 mm). Ultrasound examination revealed that hyaluronic acid materials form well-demarcated and hypoechogenic areas. Restylane 2 tended to form a more diffuse pattern, with multiple smaller bubbles, whereas Dermalax DEEP developed into a more localized configuration, with larger clumps. Conclusions: This study is the first long-term assessment of nasolabial fold correction that reveals the performance of different hyaluronic acid materials in vivo and validates high-frequency ultrasound as a simple and rapid modality. Hyaluronic acid fillers generated by different cross-linking technologies display differential diffusion patterns in skin tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

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