Simplified Aeroelastic Model for Fluid Structure Interaction between Microcantilever Sensors and Fluid Surroundings

Fluid-structural coupling occurs when microcantilever sensors vibrate in a fluid. Due to the complexity of the mechanical characteristics of microcantilevers and lack of high-precision microscopic mechanical testing instruments, effective methods for studying the fluid-structural coupling of microcantilevers are lacking, especially for non-rectangular microcantilevers. Here, we report fluid-structure interactions (FSI) of the cable-membrane structure via a macroscopic study. The simplified aeroelastic model was introduced into the microscopic field to establish a fluid-structure coupling vibration model for microcantilever sensors. We used the finite element method to solve the coupled FSI system. Based on the simplified aeroelastic model, simulation analysis of the effects of the air environment on the vibration of the commonly used rectangular microcantilever was also performed. The obtained results are consistent with the literature. The proposed model can also be applied to the auxiliary design of rectangular and non-rectangular sensors used in fluid environments.     

Encapsulating Trogtalite CoSe2 Nanobuds into BCN Nanotubes as High Storage Capacity Sodium Ion Battery Anodes

Trogtalite CoSe₂ nanobuds encapsulated into boron and nitrogen codoped graphene (BCN) nanotubes (CoSe₂@BCN‐750) are synthesized via a concurrent thermal decomposition and selenization processes. The CoSe₂@BCN‐750 nanotubes deliver an excellent storage capacity of 580 mA h g^?1 at current density of 100 mA g^?1 at 100th cycle, as the anode of a sodium ion battery. The CoSe₂@BCN‐750 nanotubes exhibit a significant rate capability (100–2000 mA g^?1 current density) and high stability (almost 98% storage retention after 4000 cycles at large current density of 8000 mA g^?1). The reasons for these excellent storage properties are illuminated by theoretical calculations of the relevant models, and various possible Na⁺ ion storage sites are identified through first‐principles calculations. These results demonstrate that the insertion of heteroatoms, B–C, N–C as well as CoSe₂, into BCN tubes, enables the observed excellent adsorption energy of Na⁺ ions in high energy storage devices, which supports the experimental results.     

Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53

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Histidine Residue Mediates Radical-induced Hinge Cleavage of Human IgG1

Hydroxyl radicals induce hinge cleavage in a human IgG1 molecule via initial radical formation at the first hinge Cys²³¹ followed by electron transfer to the upper hinge residues. To enable engineering of a stable monoclonal antibody hinge, we investigated the role of the hinge His²²⁹ residue using structure modeling and site-directed mutagenesis. Direct involvement of His²²⁹ in the reaction mechanism is suggested by a 75–85% reduction of the hinge cleavage for variants in which His²²⁹ was substituted with either Gln, Ser, or Ala. In contrast, mutation of Lys²²⁷ to Gln, Ser, or Ala increased hinge cleavage. However, the H229S/K227S double mutant shows hinge cleavage levels similar to that of the single H229S variant, further revealing the importance of His²²⁹. Examination of the hinge structure shows that His²²⁹ is capable of forming hydrogen bonds with surrounding residues. These observations led us to hypothesize that the imidazole ring of His²²⁹ may function to facilitate the cleavage by forming a transient radical center that is capable of extracting a proton from neighboring residues. The work presented here suggests the feasibility of engineering a new generation of monoclonal antibodies capable of resisting hinge cleavage to improve product stability and efficacy.     

Autophagy induction by xanthoangelol exhibits anti‐metastatic activities in hepatocellular carcinoma

Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti‐tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti‐metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3‐methyadenine (3‐MA) or knockdown of the pro‐autophagy Beclin‐1 effectively abrogated the XAG‐induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p‐AMPK while decreasing p‐mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy‐mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti‐metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti‐tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti‐metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC.     

Identification of two clip domain serine proteases involved in the pea aphid's defense against bacterial and fungal infection

Phenoloxidases (POs) are required for the pea aphid's defense against bacterial and fungal infection. Prophenoloxidases (PPOs) are proteolytically converted to its active form PO through a clip domain serine protease cascade. In this study, we identified five clip domain serine proteases in the pea aphids. The messenger RNA levels of two of them, Ap_SPLP and Ap_VP, were upregulated by Gram‐positive bacterium Staphylococcus aureus and fungus Beauveria bassiana infections. Double‐stranded RNA‐based expression knockdown of these two genes resulted in reduced PO activity of the aphid hemolymph, higher loads of S. aureus and B. bassiana in the aphids, and lower survival rates of the aphids after infections. Our data suggest that Ap_SPLP and Ap_VP are involved in PPO activation pathway in the pea aphid.