The COVID-19 pandemic caused by SARS-CoV-2 infection has placed health systems under excessive pressure and especially elderly people with cancer. Glioblastoma multiforme (GBM) is a malignant brain tumor with an increasing incidence in elderly individuals, and thereby GBM patients are a vulnerable population during the COVID-19 outbreak. Accumulating studies have implied that SARS-CoV-2 might invade the brain directlyviacoronavirus receptors. However, little is known about SARS-CoV-2 infection in the clinical development of GBM. Here, we explored the oncogenic roles of six coronavirus receptors (ACE2, DPP4, ANPEP, AXL, TMPRSS2, and ENPEP) in GBM using bioinformatics and experimental approaches. We found that ANPEP and ENPEP were significantly increased at both the mRNA and protein levels in GBM compared with normal brain tissue. Kaplan–Meier survival curves and Cox regression analysis demonstrated that high expressions ofANPEPandENPEPare associated with poor prognosis and survival. Moreover, all receptors are positively correlated with the immune infiltration levels of monocyte. Furthermore, we identified 245 genes between COVID-19 and coronavirus receptors–correlated genes in GBM and performed a thorough analysis of their protein–protein interaction network, functional signaling pathway and molecular process. Our work explores for the first time the association of coronavirus receptors with GBM and suggests ANPEP and ENPEP as potential therapeutic targets of GBM irrespective of COVID-19.

The group of receptor-interacting protein (RIP) kinases has seven members (RIPK1–7), with one homologous kinase domain but distinct non-kinase regions. Although RIPK1–3 have emerged as key modulators of inflammation and cell death, few studies have connected RIPK4–7 to immune responses. The divergence in domain structures and paralogue information in the Ensembl database have raised question about the phylogeny of RIPK1–7. In this study, phylogenetic trees of RIPK1–7 and paralogues constructed using full-length amino acid sequences or Kinase domain demonstrate that RIPK6 and RIPK7 are distinct from RIPK1–5 and paralogues shown in the Ensembl database are inaccurate. Comparative and evolutionary analyses were subsequently performed to gain new clues about the potential functions of RIPK3–7. RIPK3 gene loss in birds and animals that undergo torpor, a common physiological phenomenon in cold environments, implies that RIPK3 may be involved in ischemia-reperfusion injury and/or high metabolic rate. The negligible expression of RIPK4 and RIPK5 in immune cells is likely responsible for the lack of studies on the direct role of these members in immunity; RIPK6 and RIPK7 are conserved among plants, invertebrates and vertebrates, and dominantly expressed in innate immune cells, indicating their roles in innate immunity. Overall, our results provide insights into the multifaceted and conserved biochemical functions of RIP kinases.

The risk of childhood diarrhea related to compound drought and heatwave (CDHW) remain unclear at present and in the future under climate change scenarios. We used information on diarrhea prevalence from the Demographic and Health Surveys. Three indicators considering heatwave frequency (HWF), intensity (HWEMD), and cumulative heat (CH) were used. CDHW was defined as drought and heatwave occurred simultaneously. A modified Poisson regression model was employed to estimate the association between CDHW and diarrhea. Then the association was used to project the excess risk of CDHW-related childhood diarrhea by climate zones and regions under different climate scenarios. A total of 64,429 children under five years were included. The relative risk (RR) of CDHWs (e.g., compound severe HWF and severe drought; RR = 1.392, 95 %CI: 1.247-1.553) were significantly higher than heatwave alone (e.g., severe HWF only; RR = 1.150, 95 %CI: 1.044-1.268). The effect of severe CDHWs disappeared from subgroups with low to high Water, sanitation and hygiene (WASH) scores. The average excess risk (ER) per hot season attributed to compound drought and HWF increased by 16.4-84.8 % during 2021-2100 under various climate change scenarios. Future CDHW-related ER of childhood diarrhea varied by climate zones and geographic regions. There was a stronger association between CDHW and diarrhea risk than that of heatwave alone, while good WASH had a potential protective effect. Our findings highlight the need of integrated public health and climate adaptation strategies to address the escalating burden of childhood diarrhea associated with compound climate extremes.

Infectious diarrhea imposes substantial disease burden in China, with local climate identified as a key risk factor. In this study, we aimed to explore the association between hydrometeorological conditions and the incidence of infectious diarrhea, and investigate the modification effect of urbanization, which remained unclear previously. Monthly data were collected from 1 January 2021 to 31 December 2022 from each city of mainland China on cases of infectious diarrhea other than cholera, dysentery, typhoid and paratyphoid (i.e. other infectious diarrhea, OID), temperature and precipitation. We used Palmer drought severity index (PDSI) to represent local hydrometeorological conditions (dry and wet). A spatiotemporal Bayesian hierarchical model combined with distributed lag nonlinear model was specified to explore the association between PDSI and the relative risk of OID. The effect size of hydrometeorological conditions at different urbanization levels were quantified through a linear interaction term. A total of 1999 947 OID cases were included. There was a N-shaped cumulative association between PDSI and OID incidence over a maximum lag of 4 months. The effect of extreme dry conditions persisted over lag 1–3 months and peaked at the 2-month lag (RR = 2.67, 95%CI: 2.44–2.91). By contrast, the relative risk of OID increased immediately under extreme wet conditions (RR = 1.97, 95%CI: 1.68–2.32 at lag 0 month). Children and the older population were particularly susceptible to extreme dry and wet conditions, respectively. Areas with lower urbanization rate, healthcare resources and economic levels, and higher population density showed a higher risk of OID related to extreme dry conditions. While the modification effects of these urbanization characteristics were limited for extreme wet conditions. There was a nonlinear and lagged association between hydrometeorological conditions and the incidence of OID in mainland China, which may be modified in diverse patterns by urbanization indicators. Our findings will provide valuable reference for better prevention and control of OID.