The main objective of the present numerical analysis is to predict the nonlinear frequency ratios associated with the nonlinear free vibration response of porous composite plates at microscale in the presence of different microstructural gradient tensors. To achieve this end, by taking cubic-type elements into account, isogeometric models of porous composite microplates are obtained with and without a central cutout and relevant to various porosity patterns of distribution along the plate thickness. The established unconventional models have the capability to capture the effects of various unconventional gradient tensors continuity on the basis of a refined shear deformable plate formulation. For the simply supported microsized uniform porous functionally graded material (U-PFGM) plate having the oscillation amplitude equal to the plate thickness, it is revealed that the rotation gradient tensor causes to reduce the frequency ratio about 0.73%, the dilatation gradient tensor causes to reduce it about 1.93%, and the deviatoric stretch gradient tensor leads to a decrease of it about 5.19%. On the other hand, for the clamped microsized U-PFGM plate having the oscillation amplitude equal to the plate thickness, these percentages are equal to 0.62%, 1.64%, and 4.40%, respectively. Accordingly, it is found that by changing the boundary conditions from clamped to simply supported, the effect of microsize on the reduction of frequency ratio decreases a bit.
The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N-acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC)3], and optimized the pharmacokinetics profile of CBS in vivo. Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PLpro), main protease (Mpro), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections.A cocktail therapy comprising bismuth drugs and N-acetyl-l-cysteine is reported to suppress the replication of SARS-CoV-2 via the oral route. The broad-spectrum inhibitory activities of the combination upon key viral cysteine enzymes are verified.相似文献
A shear-lag model is used to study the mechanical properties of bone-like hierarchical materials.The relationship between the overall effective modulus and the number of hierarchy level is obtained.The result is compared with that based on the tension-shear chain model and finite element simulation,respectively.It is shown that all three models can be used to describe the mechanical behavior of the hierarchical material when the number of hierarchy levels is small.By increasing the number of hierarchy level,the shear-lag result is consistent with the finite element result.However the tension-shear chain model leads to an opposite trend.The transition point position depends on the fraction of hard phase,aspect ratio and modulus ratio of hard phase to soft phase.Further discussion is performed on the flaw tolerance size and strength of hierarchical materials based on the shear-lag analysis. 相似文献