Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing.
Methods:
In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg
2+
and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated
in vitro
and
in vivo
. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests.
Results:
The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg
2+
promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing.
Conclusions:
The composite hydrogel mediated sustained
in situ
release of curcumin and Mg
2+
to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.
As a prominent epigenetic modification, cytosine methylation may play a critical role in the adaptation of plants to different environments. The present study sought to investigate possible impacts of differential levels of nitrogen (N) supply on cytosine-methylation levels of a clonal plant, Hierochloe glabra Trin. (Poaceae). For this purpose, nitrate was applied at concentrations of 0, 0.15, 0.30 and 0.45 g N kg–1 soil, and ecologically important morphological traits were measured. The methylation-sensitive amplification polymorphism method was also conducted to analyse the variations in DNA cytosine methylation. Our results showed that N addition reduced CHG cytosine-methylation levels markedly compared with control plants growing in homogeneous pots (P = 0.026). No substantial differences were observed in morphological traits at the end of the growing stage, except for the highest ratio of leaf area to leaf dry mass in the medium-N patch (P = 0.008). However, significant linear regression relationships were found between cytosine-methylation levels and morphological traits, such as bud number and rhizome length and biomass. In conclusion, the higher cytosine-methylation level may activate asexual reproduction to produce more offspring and expand plant populations, possibly helping clonal plants to adapt to heterogeneous habitats.
Objective: The studies have produced contradictory results regarding the association between myasthenia gravis (MG) and cognitive function, especially for the cognitive domains of memory. This meta-analysis was dedicated to exploring the association between MG and memory, which was represented by the immediate recall and delayed recall.Methods: Using the random effects models, this study analyzed memory in MG based on data from the studies retrieved from four electronic databases from inception to February 2021. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. We defined ocular myasthenia gravis (OMG) (MGFA Grade I) as Class I, mild, and moderate generalized myasthenia gravis (GMG) (MGFA Grade IIa, IIb, IIIa, and IIIb) as Class II.Results: In total, eight studies of 274 patients and 211 healthy controls were included. The significant associations were found between MG and memory. Compared with the healthy control group, the patients with MG performed significantly worse in the terms of immediate recall [standardized mean difference (SMD) = −0.65, 95% CI = −0.97 to −0.33, P < 0.001, I2 = 64.1%] and delayed recall (SMD = −0.49, 95% CI = −0.88 to −0.1, P < 0.05, I2 = 76.3%). Compared with the patients with Class I MG, those with Class II MG did not have significantly different scores in immediate recall (SMD = −0.07, 95% CI = −0.35 to 0.21, P = 0.614, I2 = 0%) and delayed recall (SMD = 0.63, 95% CI = −0.29 to 1.55, P = 0.178, I2 = 87.9%).Conclusion: The patients with MG showed lower memory performance, such as both immediate and delayed recall ability. There was no association between the severity of MG and memory. Future studies should address whether these associations are casual and modifiable.
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