Increasing typhoon impact and economic losses due to anthropogenic warming in Southeast China.

Despite a variety of studies on the tropical cyclone (TC) response to climate change, few of them have examined the projected damages of future TCs. Here we quantify the impact of anthropogenic warming on TC-induced damages in the late twenty-first century along the coasts of Southeast China based on convection-permitting TC simulations and machine-learning-based damage models. We found that if the area's 10 super typhoons between 2013 and 2019 were to occur at the end of the century under the high emissions RCP8.5 scenario, they would have on average a 12% ± 4% increase in landfall intensity, 25% ± 23% increase in precipitation, and 128% ± 70% increase in economic losses, compared to historical simulations. We also found a significant increase in the full risk profile. The estimated typhoon loss with a 50-year return period for Zhejiang, Fujian, Guangdong, and Hainan (four most typhoon-prone provinces among the seven provinces in the region) would increase by 71%, 170%, 20%, and 85%, respectively, towards the end of the century even under the lower emissions RCP4.5 pathway. Our findings imply the need to design effective local hazard mitigation measures to reduce future typhoon risks.

Corrigendum: brain microvascular endothelial cell-derived HMGB1 facilitates monocyte adhesion and transmigration to promote JEV neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Corrigendum: Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.

Antioxidant and α-amylase inhibitory activities of tannic acid.

Tannic acid widely exists in plants, which forms a part of human diet. The antioxidant activity of tannic acid was evaluated by the chemical and cellular antioxidant assays. And its α-amylase inhibitory activity and behavior were also investigated. It was found that hydrogen- and electron donating capacities of tannic acid were higher than those of tertiary butylhydroquinone (TBHQ) based on reducing power, ABTS and DPPH radical scavenging assays. But for its low hydrophobic property, the antioxidant activity of tannic acid in linoleic acid system was inferior to that of TBHQ. In the cellular antioxidant assay, tannic acid showed the higher activity than gallic acid in the "PBS wash" protocol, which could attribute to its high binding capacity of cell membrane. Compared with acarbose, tannic acid possessed the stronger α-amylase inhibitory capacity. And the static fluorescence quenching of α-amylase in the presence of tannic acid could be also observed, which was caused by their binding interaction.

IP-10 Promotes Blood-Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis.

Japanese encephalitis is a neuropathological disorder caused by Japanese encephalitis virus (JEV), which is characterized by severe pathological neuroinflammation and damage to the blood-brain barrier (BBB). Inflammatory cytokines/chemokines can regulate the expression of tight junction (TJ) proteins and are believed to be a leading cause of BBB disruption, but the specific mechanisms remain unclear. IP-10 is the most abundant chemokine produced in the early stage of JEV infection, but its role in BBB disruption is unknown. The administration of IP-10-neutralizing antibody ameliorated the decrease in TJ proteins and restored BBB integrity in JEV-infected mice. In vitro study showed IP-10 and JEV treatment did not directly alter the permeability of the monolayers of endothelial cells. However, IP-10 treatment promoted tumor necrosis factor alpha (TNF-α) production and IP-10-neutralizing antibody significantly reduced the production of TNF-α. Thus, TNF-α could be a downstream cytokine of IP-10, which decreased TJ proteins and damaged BBB integrity. Further study indicated that JEV infection can stimulate upregulation of the IP-10 receptor CXCR3 on astrocytes, resulting in TNF-α production through the JNK-c-Jun signaling pathway. Consequently, TNF-α affected the expression and cellular distribution of TJs in brain microvascular endothelial cells and led to BBB damage during JEV infection. Regarding regulation of the BBB, the IP-10/TNF-α cytokine axis could be considered a potential target for the development of novel therapeutics in BBB-related neurological diseases.

Myeloid-Derived Suppressor Cells Inhibit T Follicular Helper Cell Immune Response in Japanese Encephalitis Virus Infection.

Resolution of viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. In this study, we examined Japanese encephalitis virus (JEV) infection leading to acute encephalopathy depending on suppression of the adaptive immune responses mediated by innate cells. Infection with P3 strains of JEV enhanced myeloid-derived suppressor cell (MDSC) populations, and the survival rate of JEV-infected mice improved after MDSC depletion. Mechanically, P3-induced MDSCs suppressed CD4+ T cell immune responses, especially responses of T follicular helper (Tfh) cells, leading to decreased splenic B cells (CD19+) and blood plasma cells (CD19+CD138+) and reduced levels of total IgM and JEV-specific neutralizing Abs. Upon depleting P3-induced MDSCs in vivo, the Tfh cell population, B cells, plasma cells, and Ab production recovered. These findings provide unique insights regarding MDSC functions in mediating immune suppression via inhibiting Tfh cell responses and further impairing humoral immunity, which facilitate the progression of infection.