In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone treatment is a doubleedged sword, as numerous studies have revealed that it has significant adverse impacts later in life. In this article, we reviewed the literature regarding the adverse effects of dexamethasone administration on different organ systems as well as related disease pathogenesis in an attempt to clarify the potential harms that may arise in COVID-19 patients receiving dexamethasone treatment. Overall, taking the threat of COVID-19 pandemic into account, we think it is necessary to apply dexamethasone as a pharmaceutical therapy in critical patients. However, its adverse side effects cannot be ignored. Our review will help medical professionals in the prognosis and follow-up of patients treated with dexamethasone. In addition, given that a considerable amount of uncertainty, confusion and even controversy still exist, further studies and more clinical trials are urgently needed to improve our understanding of the parameters and the effects of dexamethasone on patients with SARS-CoV-2 infection.

Background and objectives: Public health interventions have reduced coronavirus disease 2019 (COVID-19) transmission in several countries, but their impacts on COVID-19 epidemics in the USA are unclear. We examined associations of stay-at-home order (SAHO) and face-masking recommendation with COVID-19 epidemics in the USA. Methods: In this quasi-experimental interrupted time-series study, we modeled temporal trends in daily new cases and deaths of laboratory-confirmed COVID-19 cases, and COVID-19 time-varying reproduction numbers in the USA between March 1 and April 20, 2020. In addition, we conducted simulation analyses. Results: The number of residents under SAHO increased since March 19 and plateaued at 290,829,980 (88.6% of the U.S. population) on April 7. Trends in COVID-19 time-varying reproduction numbers peaked on March 23, further reduced on April 3, and fell below/around 1.0 on April 13. Early-implementation and early-lift of SAHO would reduce and increase COVID-19 epidemics, respectively. Multivariable piecewise log-linear regression revealed the states' neighboring relationship with New York was linked to COVID-19 daily new cases and deaths. There were two turning points in daily new-case trend, being March 28 (slope-changes = −0.09) and April 3 (slope-changes = −0.09), which appeared to be associated with implementation of SAHO on March 28 (affecting 48.5% of the US population in 22 states and District of Columbia), and face-masking recommendation on April 3, respectively. There were also two turning points in daily new-death trend, being April 9 (slope-changes = −0.06) and April 19 (slope-changes = −0.90). Conclusions: We identified two turning points of COVID-19 daily new cases or deaths in the USA, which seem to

Periprosthetic osteolysis (PPO) remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles. Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses. Additionally, the NLRP3 inflammasome is activated by prosthetic particles. Sirtuin3, an NAD + -dependent deacetylase of mitochondria, regulates the function of mitochondria in diverse activities. However, whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported. Therefore, we investigated the role of SIRT3 during the process of titanium (Ti) particle-induced osteolysis. We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro . Moreover, we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway. Collectively, these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.

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Periprosthetic osteolysis (PPO) and subsequent aseptic loosening are the main causes of implant failure and revision surgery. Emerging evidence has suggested that wear-particle-induced chronic inflammation, osteoblast inhibition and osteoclast formation...

Implant-derived wear particles can be phagocytosed by local macrophages, triggering an inflammatory cascade that can drive the activation and recruitment of osteoclasts, thereby inducing peri-prosthetic osteolysis. Efforts to suppress pro-inflammatory cytokine release and osteoclastsogenesis thus represent primary approaches to treating and preventing such osteolysis. Sirtuin 3 (SIRT3) is a NAD + -dependent deacetylases that control diverse metabolic processes. However, whether SIRT3 could mitigate wear debris-induced osteolysis has not been reported. Herein we explored the impact of the SIRT3 on titanium particle-induced osteolysis. Tartrate resistant acid phosphatase (TRAP) staining revealed that the inhibition of SIRT3 suppressed nuclear factor-κB ligand (RANKL)-mediated osteoclasts activation in a dose-dependent fashion. Notably, inhibition of SIRT3 also suppressed matrix metallopeptidase 9 (MMP9) and nuclear factor of activated T‐cell cytoplasmic 1 (NFATc1) expression at the mRNA and protein levels, while also inhibiting the mRNA expression of dendritic cell-specific transmembrane protein (DC-STAMP), ATPase H + Transporting V0 Subunit D2 (Atp6v0d2), TRAP and Cathepsin K (CTSK) . In addition, inhibition of SIRT3 suppressed titanium particle-induced tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) expression and prevented titanium particle-induced osteolysis and bone loss in vivo . This inhibition of osteoclasts differentiation was found to be linked to the downregulation and reduced phosphorylation of JNK and ERK. Taken together, inhibition of SIRT3 may be a potential target for titanium particle-induced bone loss.

27The COVID-19 pandemic is straining public health systems worldwide and major non-28 pharmaceutical interventions have been implemented to slow its spread [1][2][3][4] . During the initial phase 29 of the outbreak the spread was primarily determined by human mobility 5,6 . Yet empirical evidence 30 on the effect of key geographic factors on local epidemic spread is lacking 7 . We analyse highly-31 resolved spatial variables for cities in China together with case count data in order to investigate 32 the role of climate, urbanization, and variation in interventions across China. Here we show that 33 the epidemic intensity of COVID-19 is strongly shaped by crowding, such that epidemics in dense 34cities are more spread out through time, and denser cities have larger total incidence. Observed 35 differences in epidemic intensity are well captured by a metapopulation model of COVID-19 that 36 explicitly accounts for spatial hierarchies. Densely-populated cities worldwide may experience more 37 prolonged epidemics. Whilst stringent interventions can shorten the time length of these local 38 identify drivers of local transmission in Chinese cities, with a focus on epidemic intensity among 60 provinces in China. 61 62To explore the impact of urbanization, temperature, and humidity, we used daily incidence data of 63 confirmed COVID-19 cases (date of onset) aggregated at the prefectural level (n = 293) in China. 64