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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]

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]

In real systems, the unpredictable jump changes of the random environment can induce the critical transitions (CTs) between two non-adjacent states, which are more catastrophic. Taking an asymmetric Lévy-noise-induced tri-stable model with desirable, sub-desirable, and undesirable states as a prototype class of real systems, a prediction of the noise-induced CTs from the desirable state directly to the undesirable one is carried out. We first calculate the region that the current state of the given model is absorbed into the undesirable state based on the escape probability, which is named as the absorbed region. Then, a new concept of the parameter dependent basin of the unsafe regime (PDBUR) under the asymmetric Lévy noise is introduced. It is an efficient tool for approximately quantifying the ranges of the parameters, where the noise-induced CTs from the desirable state directly to the undesirable one may occur. More importantly, it may provide theoretical guidance for us to adopt some measures to avert a noise-induced catastrophic CT. [ABSTRACT FROM AUTHOR]

Predicting noise-induced critical transitions between multi-stable states of a dynamical system is of uttermost importance in various fields. This paper investigates a tri-stable model with desirable, sub-desirable and undesirable states as a prototype class of real systems. Then, two critical transitions, from the desirable state to the sub-desirable one (CT1) and from the sub-desirable state to the undesirable one (CT2), induced by Gaussian white noise are uncovered. The new results show that the noise-induced CT1 and CT2 take place before the bifurcation point of the corresponding deterministic system and this phenomenon becomes earlier with increasing noise intensity. Therefore, some precursor criteria of the noise-induced CT1 and CT2 are further explored. Firstly, the largest Lyapunov exponent and the Shannon entropy are introduced into the prediction of the noise-induced CT1 and CT2 from a new perspective. It is found that both of them are more efficient compared to the classic variance and autocorrelation at-lag-1, and the Shannon entropy is more robust as compared to CT1 and CT2 under strong fluctuations. Moreover, a range of the bifurcation parameter, where noise-induced critical transitions may occur, is approximately quantified in the parameter-dependent basin of the unsafe regime. All of these results may provide some guidance for establishing more general precursor criteria of multiple noise-induced critical transitions in the future. [ABSTRACT FROM AUTHOR]

Stochastic perturbations and periodic excitations are generally regarded as sources to induce critical transitions in complex systems. However, we find that they are also able to slow down an imminent critical transition. To illustrate this phenomenon, a periodically driven bistable eutrophication model with Gaussian white noise is introduced as a prototype class of real systems. The residence probability (RP) is presented to measure the possibility that the given system stays in the oligotrophic state versus Gaussian white noise and periodic force. Variations in the mean first passage time (MFPT) and the mean velocity (MV) of the first right-crossing process are also calculated respectively. We show that the frequency of the periodic force can increase the MFPT while reduce the MV under different control parameters. Nevertheless, the noise intensity or the amplitude may result in an increase of the RP only in the case of control parameters approaching the critical values. Furthermore, for an impending critical transition, an increase of the RP appears with the interaction between the amplitude and noise intensity or the combination of the noise intensity and frequency, while the interaction of the frequency and amplitude leads to an extension of the MFPT or a decrease of the MV. As a result, an increase of the RP and MFPT, and a decrease of the MV obtained from our results claim that it is possible to slow down an imminent critical transition via Gaussian white noise and periodic force. [ABSTRACT FROM AUTHOR]

We discuss the constructive role of combined harmonic and random excitation on stochastic resonance (SR) in a Brusselator model. We first numerically investigate SR determined by the Signal-to-Noise Ratio (SNR) in this model. Effects of different parameters on SR are described in detail. Our simulation results show that the intensity of the Gaussian colored noise and the amplitude of the periodic force can enhance SR. Moreover, an analytical framework is presented for the SNR of the Brusselator model, leading to a theoretical expression of SNR. We observe a good agreement between the theoretical and numerical results, and the effectiveness of the proposed theoretical method is verified. This theoretical analysis provides a global view on how the dynamics of a periodically forced system with noise changes in the vicinity of a Hopf bifurcation. [ABSTRACT FROM AUTHOR]

Purpose: Suture fixation is mostly used in arthroscopic treatment of tibial eminence avulsion fractures. However, no clinical studies of metal cable fixation have been reported. We hypothesised that cable fixation can provide equal stability and clinical outcome compared with Ethibond sutures. Methods: Between 2007 and 2008, we treated 42 patients of adult type III tibial eminence avulsion fractures. Twenty-three patients were male, and 19 were female. All patients were confirmed by radiographs, MRI, and arthroscopy during surgery. Ligament injury and meniscus tears were excluded from this study. Twenty-two patients were treated with No. 2 Ethibond suture fixation (group I), and 20 were treated with cable fixation under arthroscopy (group II). Follow-up assessments included imaging evaluation, Lysholm knee score, International Knee Documentation Committee (IKDC) classification, and the Lachman test. Results: Bone union was found in radiographic evaluation in all patients within 3 months. At the last follow-up, there was neither extension nor flexion limitation in any patient. There were no significant differences in the Lysholm score between the two groups at follow-up. All 42 patients were classified by the IKDC as normal or nearly normal. Stability based on the Lachman test showed two patients of grade II laxity in group I. At the final follow-up, all 42 patients had returned to their pre-injury activities. Conclusions: Cable fixation to treat type III tibial eminence avulsion fracture can provide a clinical outcome equal to that of Ethibond sutures. Level of evidence: IV. [ABSTRACT FROM AUTHOR]