ObjectivesWnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional relationship in OA progression in chondrocyte lineage.MethodsThe role of Wnt16 during skeletal development was examined by Col2a1-Wnt16 transgenic mice and Wnt16fl/fl;Col2a1-Cre (Wnt16-cKO) mice. OA progression was assessed by micro-CT analysis and Osteoarthritis Research Society International score after anterior cruciate ligament transection (ACLT) surgery with Wnt16 manipulation by adenovirus intra-articular injection. The molecular mechanism was investigated in vitro using 3D chondrocyte pellet culture and biochemical analyses. Histological analysis was performed in mouse joints and human cartilage specimens.Results Wnt16 overexpression in chondrocytes in mice significantly inhibited chondrocyte hypertrophy during skeletal development. Wnt16 deficiency exaggerated OA progression, whereas intra-articular injection of Ad-Wnt16 markedly attenuated ACLT-induced OA. Cellular and molecular analyses showed that, instead of β-catenin and calcium pathways, Wnt16 activated the planar cell polarity (PCP) and JNK pathway by interacting mainly with AP2b1, and to a lesser extend Ror2 and CD146, and subsequently induced PTHrP expression through phosphor-Raptor mTORC1 pathway.ConclusionsOur findings indicate that Wnt16 activates PCP/JNK and crosstalks with mTORC1-PTHrP pathway to inhibit chondrocyte hypertrophy. Our preclinical study suggests that Wnt16 may be a potential therapeutic target for OA treatment.

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Clinical treatments for the repair of osteochondral defects (OCD) are merely palliative, not completely curative, and thus enormously unfulfilled challenges. With the in-depth studies of biology, medicine, materials, and engineering technology, the conception of OCD repair and regeneration should be renewed. During the past decades, many innovative tissue-engineered approaches for repairing and regenerating damaged osteochondral units have been widely explored. Various scaffold-free and scaffold-based strategies, such as monophasic, biphasic, and currently fabricated multiphasic and gradient architectures have been proposed and evaluated. Meanwhile, progenitor cells and tissue-specific cells have also been intensively investigated in vivo as well as ex vivo. Concerning bioactive factors and drugs, they have been combined with scaffolds and/or living cells, and even released in a spatiotemporally controlled manner. Although tremendous progress has been achieved, further research and development (R&D) is needed to convert preclinical outcomes into clinical applications. Here, the osteochondral unit structure, its defect classifications, and diagnosis are summarized. Commonly used clinical reparative techniques, tissue-engineered strategies, emerging 3D-bioprinting technologies, and the status of their clinical applications are discussed. Existing challenges to translation are also discussed and potential solutions for future R&D directions are proposed.

SummaryThe role of neuroimaging in the assessment of a firstever seizure has not been well-defined, in particular the utility of MRI when CT is normal. The results of neuroimaging (CT brain, MRI brain, or both) in 1,013 adults with first-ever unprovoked seizure were correlated with clinical features and seizure outcome. Epileptogenic lesions were identified in 29%. Of patients with a normal CT who also had MRI, 12% had an epileptogenic lesion on MRI, the strongest independent predictor of which was a focal abnormality on EEG. Patients with an epileptogenic lesion had a higher risk of seizure recurrence, including when this was only evident on MRI.

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Across the latter half of 2019, Hong Kong became the focus of world attention as it was rocked by a wave of increasingly violent confrontations between police and protesters. Both inside and outside the Territory, several powerful political actors have argued that the paramilitary-style police interventions used to manage the protests were necessary because the disorder was being fermented by agitators. In contrast, this article explores the utility of the Elaborated Social Identity Model of crowd behaviour to help explore and explain some of the social psychological dynamics through which the 2019 protests became ‘radicalised’. The article explores three key phases of their evolution to draw out the patterns of collective action and variations in policing approaches. We show that early demonstrations were focused predominantly on preventing the implementation of controversial legislation but spread and changed in form as a function of the use of crowd dispersal tactics by police. Moreover, we show how police inaction at other critical moments helped amplify perceptions of police illegitimacy that further radicalized protesters. Drawing upon a body of primary interview and secondary survey data, we also provide a social psychological analysis. We argue the observed patterns of collective action were underpinned by identity change and empowerment processes brought about as a consequence of both the structural context and the intergroup dynamics created in part by coercive policing practices.

This article analyzes Taiwan’s National Epidemic Prevention Team, a collective synergy between government and society in fighting COVID-19. We draw on a model of collaborative governance to dissect the collaboration between National Epidemic Prevention Team members; that is, central government, local governments, private enterprises and citizens. We argue that the 2003 severe acute respiratory syndrome (SARS) outbreak, democratic deepening and continual diplomatic isolation despite the global health crisis contributed to Taiwan’s National Epidemic Prevention Team capacity and cohesiveness. Our analysis contributes to the heated discourse on democratic resilience in these turbulent times, suggesting that outbreak control can succeed only if there is an integrated system of interdepartmental, central–local, intersectoral and citizen–state collaboration. Overall, this article shows how liberal democracies can control and counteract COVID-19 without resorting to authoritarian methods of containment.