A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

Graphene-like two-dimensional materials (2DMats) show application potential in optoelectronics and biomedicine due to their unique properties. However, environmental and biological influences of these 2DMats remain to be unveiled. Here we reported the antibacterial activity of two-dimensional (2D) chemically exfoliated MoS₂ (ce-MoS₂) sheets. We found that the antibacterial activity of ce-MoS₂ sheets was much more potent than that of the raw MoS₂ powders used for the synthesis of ce-MoS₂ sheets possibly due to the 2D planar structure (high specific surface area) and higher conductivity of the ce-MoS₂. We investigated the antibacterial mechanisms of the ce-MoS₂ sheets and proposed their antibacterial pathways. We found that the ce-MoS₂ sheets could produce reactive oxygen species (ROS), different from a previous report on graphene-based materials. Particularly, the oxidation capacity of the ce-MoS₂ sheets toward glutathione oxidation showed a time and concentration dependent trend, which is fully consistent with the antibacterial behaviour of the ce-MoS₂ sheets. The results suggest that antimicrobial behaviors were attributable to both membrane and oxidation stress. The antibacterial pathways include MoS₂–bacteria contact induced membrane stress, superoxide anion (O₂˙⁻) induced ROS production by the ce-MoS₂, and the ensuing superoxide anion-independent oxidation. Our study thus indicates that the tailoring of the dimension of nanomaterials and their electronic properties would manipulate antibacterial activity.

Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.

Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.