Intracerebral hemorrhage (ICH) is a common acute nervous system disease with high mortality and severe disability. Mesenchymal stem cells (MSCs) have been reported to promote neurogenesis and to alleviate side effects in areas of brain injury areas. The Hippo pathway regulates diverse cellular processes, including cell survival, proliferation, differentiation, and organ size. Here, we found that transplantation of bone marrow MSCs (BM-MSCs) into the brains of mice could alleviate ICH-mediated injury and protect astrocytes from apoptosis by regulating mammalian sterile 20-like kinase (MST)1 and Yes-associated protein (YAP). Knocking down of MST1 by si-RNA triggered YAP nuclear translocation. We further demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and become capable of proliferating after BM-MSC transplantation via the Hippo signaling pathway. Together, our identification of the Hippo pathway in mediating the beneficial effects of BM-MSCs may provide a novel therapeutic target in the treatment and management of ICH.

The large proportion of asymptomatic patients is the major cause leading to the COVID-19 pandemic which is still a significant threat to the whole world. A six-dimensional ODE system (SEIAQR epidemical model) is established to study the dynamics of COVID-19 spreading considering infection by exposed, infected, and asymptomatic cases. The basic reproduction number derived from the model is more comprehensive including the contribution from the exposed, infected, and asymptomatic patients. For this more complex six-dimensional ODE system, we investigate the global and local stability of disease-free equilibrium, as well as the endemic equilibrium, whereas most studies overlooked asymptomatic infection or some other virus transmission features. In the sensitivity analysis, the parameters related to the asymptomatic play a significant role not only in the basic reproduction number $R_0$. It is also found that the asymptomatic infection greatly affected the endemic equilibrium. Either in completely eradicating the disease or achieving a more realistic goal to reduce the COVID-19 cases in an endemic equilibrium, the importance of controlling the asymptomatic infection should be emphasized. The three-dimensional phase diagrams demonstrate the convergence point of the COVID-19 spreading under different initial conditions. In particular, massive infections will occur as shown in the phase diagram quantitatively in the case $R_0>1$. Moreover, two four-dimensional contour maps of $R_t$ are given varying with different parameters, which can offer better intuitive instructions on the control of the pandemic by adjusting policy-related parameters.

To assess the effectiveness of the containment strategies proposed in Japan, an SEIAQR (susceptible-exposed-infected-asymptomatic-quarantined-recovered) model was established to simulate the transmission of COVID-19. We divided the spread of COVID-19 in Japan into different stages based on policies. The effective reproduction number $R_e$ and the transmission parameters were determined to evaluate the measures conducted by the Japanese Government during these periods. On 7 April 2020, the Japanese authority declared a state of emergency to control the rapid development of the pandemic. Based on the simulation results, the spread of COVID-19 in Japan can be inhibited by containment actions during the state of emergency. The effective reproduction number $R_e$ reduced from 1.99 (before the state of emergency) to 0.92 (after the state of emergency). The transmission parameters were fitted and characterized with quantifiable variables including the ratio of untracked cases, the PCR test index and the proportion of COCOA app users (official contact confirming application). The impact of these variables on the control of COVID-19 was investigated in the modelling analysis. On 8 January 2021, the Japanese Government declared another state of emergency. The simulated results demonstrated that the spread could be controlled in May by keeping the same strategies. A higher intensity of PCR testing was suggested, and a larger proportion of COCOA app users should reduce the final number of infections and the time needed to control the spread of COVID-19.