Climate change is often described as the average changes in temperature and precipitation; however, it is the change in climate extremes determines the levels of socioeconomic impacts related to climate change. It is generally believed that global warming drives increase in frequency, intensity and duration of precipitation extremes, but these changes vary regionally. Focusing on the relationships between evolution of extreme events and long-term climate change, here we propose a novel classification scheme based on Kӧppen's system and changes in mean and variability of precipitation, divide the global climate into 20 different changing types and reveal the regional evolution of precipitation extremes. We find that precipitation extremes ascend significantly in wetting regions, especially in tropical and temperate zones, independent with changed variability. As for drying regions, the evolution of extremes is related to precipitation variability. An increase of extremes can still be detected in fluctuant-drying areas, while a slight decrease can be seen in stabilized-drying areas. It is surprising to find increase in both wetness and dryness extremes which implies higher intensity of meteorological hazards in densely populated areas. Based on the current and projected growth of population exposure to precipitation extremes, we identify some hotspots with high potential risk in the future.

An engineered RNase P-based ribozyme variant, which was generated using the in vitro selection procedure, was used to target the overlapping mRNA region of two proteins essential for human cytomegalovirus (HCMV) replication: capsid assembly protein (AP) and protease (PR). In vitro studies showed that the generated variant, V718-A, cleaved the target AP mRNA sequence efficiently and its activity was about 60-fold higher than that of wild type ribozyme M1-A. Furthermore, we observed a reduction of 98%-99% in AP/PR expression and an inhibition of 50,000 fold in viral growth in cells with V718-A, while a 75% reduction in AP/PR expression and a 500-fold inhibition in viral growth was found in cells with M1-A. Examination of the antiviral effects of the generated ribozyme on the HCMV replication cycle suggested that viral DNA encapsidation was inhibited and as a consequence, viral capsid assembly was blocked when the expression of AP and PR was inhibited by the ribozyme. Thus, our study indicates that the generated ribozyme variant is highly effective in inhibiting HCMV gene expression and blocking viral replication, and suggests that engineered RNase P ribozyme can be potentially developed as a promising gene-targeting agent for anti-HCMV therapy.

The precise cell type hosting latent human cytomegalovirus (HCMV) remains elusive. Here, we report that HCMV reprogrammes human haematopoietic progenitor cells (HPCs) into a unique monocyte subset to achieve latency. Unlike conventional monocytes, this monocyte subset possesses higher levels of B7-H4, IL-10 and inducible nitric oxide synthase (iNOS), a longer lifespan and strong immunosuppressive capacity. Cell sorting of peripheral blood from latently infected human donors confirms that only this monocyte subset, representing less than 0.1% of peripheral mononuclear cells, is HCMV genome-positive but immediate-early-negative. Mechanistic studies demonstrate that HCMV promotes the differentiation of HPCs into this monocyte subset by activating cellular signal transducer and activator of transcription 3 (STAT3). In turn, this monocyte subset generates a high level of nitric oxide (NO) to silence HCMV immediate-early transcription and promote viral latency. By contrast, the US28-knockout HCMV mutant, which is incapable of activating STAT3, fails to reprogramme the HPCs and achieve latency. Our findings reveal that via activating the STAT3-iNOS-NO axis, HCMV differentiates human HPCs into a longevous, immunosuppressive monocyte subset for viral latency.

The International Initiative on Spatial Lifecourse Epidemiology (ISLE) convened its first International Symposium on Lifecourse Epidemiology and Spatial Science at the Lorentz Center in Leiden, Netherlands, 16–20 July 2018. Its aim was to further an emerging transdisciplinary field: Spatial Lifecourse Epidemiology. This field draws from a broad perspective of scientific disciplines including lifecourse epidemiology, environmental epidemiology, community health, spatial science, health geography, biostatistics, spatial statistics, environmental science, climate change, exposure science, health economics, evidence-based public health, and landscape ecology. The participants, spanning 30 institutions in 10 countries, sought to identify the key issues and research priorities in spatial lifecourse epidemiology. The results published here are a synthesis of the top 10 list that emerged out of the discussion by a panel of leading experts, reflecting a set of grand challenges for spatial lifecourse epidemiology in the coming years. https://doi.org/10.1289/EHP4868.

The International Initiative on Spatial Lifecourse Epidemiology (ISLE) convened its first International Symposium on Lifecourse Epidemiology and Spatial Science at the Lorentz Center in Leiden, Netherlands, 16–20 July 2018. Its aim was to further an emerging transdisciplinary field: Spatial Lifecourse Epidemiology. This field draws from a broad perspective of scientific disciplines including lifecourse epidemiology, environmental epidemiology, community health, spatial science, health geography, biostatistics, spatial statistics, environmental science, climate change, exposure science, health economics, evidence-based public health, and landscape ecology. The participants, spanning 30 institutions in 10 countries, sought to identify the key issues and research priorities in spatial lifecourse epidemiology. The results published here are a synthesis of the top 10 list that emerged out of the discussion by a panel of leading experts, reflecting a set of grand challenges for spatial lifecourse epidemiology in the coming years. https://doi.org/10.1289/EHP4868.

A major threat to rice production is the disease epidemics caused by insect-borne viruses that emerge and re-emerge with undefined origins. It is well known that some human viruses have zoonotic origins from wild animals. However, it remains unknown whether native plants host uncharacterized endemic viruses with spillover potential to rice (Oryza sativa) as emerging pathogens. Here, we discovered rice tiller inhibition virus (RTIV), a novel RNA virus species, from colonies of Asian wild rice (O. rufipogon) in a genetic reserve by metagenomic sequencing. We identified the specific aphid vector that is able to transmit RTIV and found that RTIV would cause low-tillering disease in rice cultivar after transmission. We further demonstrated that an infectious molecular clone of RTIV initiated systemic infection and causes low-tillering disease in an elite rice variety after Agrobacterium-mediated inoculation or stable plant transformation, and RTIV can also be transmitted from transgenic rice plant through its aphid vector to cause disease. Finally, global transcriptome analysis indicated that RTIV may disturb defense and tillering pathway to cause low tillering disease in rice cultivar. Thus, our results show that new rice viral pathogens can emerge from native habitats, and RTIV, a rare aphid-transmitted rice viral pathogen from native wild rice, can threaten the production of rice cultivar after spillover.

The global urbanization rate is accelerating; however, data limitations have far prevented robust estimations of either global urban expansion or its effects on terrestrial net primary productivity (NPP). Here, using a high resolution dataset of global land use/cover (GlobeLand30), we show that global urban areas expanded by an average of 5694 km² per year between 2000 and 2010. The rapid urban expansion in the past decade has in turn reduced global terrestrial NPP, with a net loss of 22.4 Tg Carbon per year (Tg C year^-1). Although small compared to total terrestrial NPP and fossil fuel carbon emissions worldwide, the urbanization-induced decrease in NPP offset 30% of the climate-driven increase (73.6 Tg C year^-1) over the same period. Our findings highlight the urgent need for global strategies to address urban expansion, enhance natural carbon sinks, and increase agricultural productivity.

Spatial lifecourse epidemiology is an interdisciplinary field that utilizes advanced spatial, location-based, and artificial intelligence technologies to investigate the long-term effects of environmental, behavioural, psychosocial, and biological factors on health-related states and events and the underlying mechanisms. With the growing number of studies reporting findings from this field and the critical need for public health and policy decisions to be based on the strongest science possible, transparency and clarity in reporting in spatial lifecourse epidemiologic studies is essential. A task force supported by the International Initiative on Spatial Lifecourse Epidemiology (ISLE) identified a need for guidance in this area and developed a Spatial Lifecourse Epidemiology Reporting Standards (ISLE-ReSt) Statement. The aim is to provide a checklist of recommendations to improve and make more consistent reporting of spatial lifecourse epidemiologic studies. The STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement for cohort studies was identified as an appropriate starting point to provide initial items to consider for inclusion. Reporting standards for spatial data and methods were then integrated to form a single comprehensive checklist of reporting recommendations. The strength of our approach has been our international and multidisciplinary team of content experts and contributors who represent a wide range of relevant scientific conventions, and our adherence to international norms for the development of reporting guidelines. As spatial, location-based, and artificial intelligence technologies used in spatial lifecourse epidemiology continue to evolve at a rapid pace, it will be necessary to revisit and adapt the ISLE-ReSt at least every 2-3 years from its release.