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In stochastic complex systems, some sudden critical transitions (CTs) from one desirable state to another contrasting one can take place because of noise, which may even lead to catastrophic consequences. To keep a certain system in one desirable state of performance, methods that suppress these catastrophic CTs in the presence of noise need to be developed. In this paper, the ability of an external linear augmentation method to suppress Gaussian white noise-induced CTs away from a desirable state is investigated from a new perspective. This control is designed in such a way that, as a noise-induced CT is impending, the desirable state of performance in a stochastic complex system can be stabilized using a specific type of coupling with a linear dynamical system. Then, the contrasting state is annihilated with increasing coupling strength. Taking a bi-stable system with one CT (from the desirable state to the undesirable one) and a tri-stable system with two CTs (from the desirable state to the sub-desirable one and from the sub-desirable state to the undesirable one) as the prototype class of real complex systems, the potential of our technique is demonstrated. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA. [ABSTRACT FROM AUTHOR]