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Circadian rhythm perturbations can impact the evolution of different conditions, including autoimmune diseases. This narrative review summarizes the current understanding of circadian biology in inflammatory joint diseases and discusses the potential application of chronotherapy. Proinflammatory cytokines are key players in the development and progression of rheumatoid arthritis (RA), regulating cell survival/apoptosis, differentiation, and proliferation. The production and secretion of inflammatory cytokines show a dependence on the human day–night cycle, resulting in changing cytokine plasma levels over 24 h. Moreover, beyond the circadian rhythm of cytokine secretion, disturbances in timekeeping mechanisms have been proposed in RA. Taking into consideration chronotherapy concepts, modified-release (MR) prednisone tablets have been introduced to counteract the negative effects of night-time peaks of proinflammatory cytokines. Low-dose MR prednisone seems to be able to improve the course of RA, reduce morning stiffness and morning serum levels of IL-6, and induce significant clinical benefits. Additionally, methotrexate (MTX) chronotherapy has been reported to be associated with a significant improvement in RA activity score. Similar effects have been described for polymyalgia rheumatica and gout, although the available literature is still limited. Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects. Full article

As a system of ranging and positioning based on time transfer, the timekeeping ability of a navigation satellite constellation is a key factor for accurate positioning and timing services. As the timekeeping performances depend on the frequency stability and predictability of satellite clocks, we propose a method to establish a more stable and predictable space time reference, i.e., inter-satellite link time (ISLT), uniting the satellite clocks through inter-satellite links (ISLs). The joint timekeeping framework is introduced first. Based on the weighted average timescale algorithm, the optimal weights that minimize the increment of the ISLT timescale are determined and allocated to the clock ensemble to improve the frequency stability and predictability in both the long and short term. The time deviations with respect to the system time of nine BeiDou-3 satellites through multi-satellite precise orbit determination (MPOD) are used for joint timekeeping evaluation. According to the Allan deviation, the frequency of the ISLT is more stable than the nine satellite clocks in the short term (averaging time smaller than 7000 s), and its daily stability can reach 6 × 10⁻¹⁵. Meanwhile, the short-term (two hours) and long-term (10 h) prediction accuracy of the ISLT is 0.18 and 1.05 ns, respectively, also better than each satellite clock. Furthermore, the joint timekeeping is verified to be robust against single-satellite malfunction. Full article