Nonpharmaceutical interventions (NPIs) have been employed to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet these measures are already having similar ...effects on other directly transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America: respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the United States at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021–2022. Longer NPIs, in general, lead to larger future outbreaks although they may display complex interactions with baseline seasonality. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.
Preliminary evidence suggests that climate may modulate the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet it remains unclear whether seasonal and geographic ...variations in climate can substantially alter the pandemic trajectory, given that high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic by probing different scenarios based on known coronavirus biology. We find that although variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen, the climate drives only modest changes to pandemic size. A preliminary analysis of nonpharmaceutical control measures indicates that they may moderate the pandemic-climate interaction through susceptible depletion. Our findings suggest that without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.
The most recent generation of climate models (the 6th Phase of the Coupled Model Intercomparison Project) yields estimates of effective climate sensitivity (ECS) that are much higher than past ...generations due to a stronger amplification from cloud feedback. If plausible, these models require substantially larger greenhouse gas reductions to meet global warming targets. We show that models with a more positive cloud feedback also have a stronger cooling effect from aerosol‐cloud interactions. These two effects offset each other during the historical period when both aerosols and greenhouse gases increase, allowing either more positive or neutral cloud feedback models to reproduce the observed global‐mean temperature change. Since anthropogenic aerosols primarily concentrate in the Northern Hemisphere, strong aerosol‐cloud interaction models produce an interhemispheric asymmetric warming. We show that the observed warming asymmetry during the mid to late 20th century is more consistent with low ECS (weak aerosol indirect effect) models.
Plain Language Summary
The response of clouds to surface temperature change can amplify or dampen the greenhouse gas induced warming, also known as cloud feedback. We find that in the latest generation of climate models, those models with a more positive cloud feedback tend to have a stronger cooling effect from aerosol‐cloud interaction. The compensation between cloud feedback and aerosol‐cloud interaction enables models to reproduce the historical global‐mean temperature change. In spite of having significantly different surface temperature sensitivity to increasing CO2, the historical record of global‐mean temperature is not a strong constraint in distinguishing these models. However, the interhemispheric difference in temperature over the 20th century provides a constraint that distinguishes the models that have a large or small sensitivity to increasing CO2. Over the 20th century, changes in anthropogenic aerosols were mostly concentrated in the Northern Hemisphere. Consequently, models with strong or weak aerosol‐cloud interactions produce different warming asymmetry over the historical period, and the observed warming asymmetry is more consistent with the models that have weak aerosol‐cloud interactions (and less positive cloud feedback). This study can help us better understand and reduce the uncertainty in the projected future warming.
Key Points
Models with more positive cloud feedback tend to have more negative aerosol‐cloud interaction
This compensation relationship enables the models to match the historical warming even with a large spread in climate sensitivity
Historical interhemispheric warming indicates the high climate sensitivity models overestimate the aerosol‐cloud interaction
East African precipitation is characterized by a dry annual mean climatology compared to other deep tropical land areas and a bimodal annual cycle with the major rainy season during March–May (MAM; ...often called the “long rains”) and the second during October–December (OND; often called the “short rains”). To explore these distinctive features, ERA-Interim data are used to analyze the associated annual cycles of atmospheric convective stability, circulation, and moisture budget. The atmosphere over East Africa is found to be convectively stable in general year-round but with an annual cycle dominated by the surface moist static energy (MSE), which is in phase with the precipitation annual cycle. Throughout the year, the atmospheric circulation is dominated by a pattern of convergence near the surface, divergence in the lower troposphere, and convergence again at upper levels. Consistently, the convergence of the vertically integrated moisture flux is mostly negative across the year, but becomes weakly positive in the two rainy seasons. It is suggested that the semiarid/arid climate in East Africa and its bimodal precipitation annual cycle can be explained by the ventilation mechanism, in which the atmospheric convective stability over East Africa is controlled by the import of low MSE air from the relatively cool Indian Ocean off the coast. During the rainy seasons, however, the off-coast sea surface temperature (SST) increases (and is warmest during the long rains season) and consequently the air imported into East Africa becomes less stable. This analysis may be used to aid in understanding overestimates of the East African short rains commonly found in coupled models.
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Acute liver injury (ALI) caused by sepsis is a fearful disease with high mortality and poor prognosis. This study aimed to explore the roles and mechanism of Maresin 1 (MaR1) in ...lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI.
We established an ALI mouse model induced by LPS/D-GalN. Each group was treated with or without LPS/D-GalN or MaR1. For the vitro experiments, RAW264.7, NCTC1469 cells, and bone marrow-derived macrophages (BMDMs) were stimulated with LPS. The effects of MaR1 on the reactive oxygen species (ROS), pyroptosis and inflammatory response in macrophages were investigated.
MaR1 significantly inhibited an excessive inflammatory response and proinflammatory markers during LPS/D-GalN-induced ALI. MaR1 markedly decreased the levels of ROS, tumor necrosis factor-α, and interleukin-1β (IL-1β) in macrophages, and limited hepatocyte apoptosis in vitro. Upon exploring the mechanisms underlying the protective role of MaR1, we found MaR1 markedly upregulated the nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and considerably reduced the phosphorylation of p38, ERK, and nuclear factor-kappa B (NF-κB)-p65. Knocking down Nrf2 decreased the effect of MaR1. Furthermore, we observed that MaR1 reduced inflammatory injury by inhibiting M1 macrophages and promoting M2 macrophage polarization. Finally, we observed that MaR1 could inhibit the production of gasdermin D N-terminus (GSDMD-N) in vivo. In vitro, MaR1 could significantly suppressed the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome, GSDMD-N, and IL-1β caused by LPS and nigericin stimulation in BMDMs.
MaR1 could ameliorate inflammation during LPS/D-GalN induced ALI by suppressing mitogen-activated protein kinase /NF-κB signaling and NLRP3 inflammasome-induced pyroptosis, activating macrophage M1/M2 polarization and Nrf2/HO-1 signaling. This provides new evidence for the potential of developing MaR1 for ALI treatment.
Decadal variability of the East African precipitation during the season of March–May (long rains) is examined and the performance of a series of models in simulating the observed features is ...assessed. Observational results show that the drying trend of the long rains is associated with decadal natural variability associated with sea surface temperature (SST) variations over the Pacific Ocean. Empirical orthogonal function (EOF), linear regression, and composite analyses all show the spatial pattern of the associated SST field to be La Niña like. The SST-forced International Research Institute for Climate and Society (IRI) forecast models are able to capture the East African precipitation climatology, the decadal variability of the long rains, and the associated SST anomaly pattern but are not consistent with observations from the 1970s. The multimodel mean of the SST-forced models from the Coupled Model Intercomparison Project phase 5 (CMIP5) Atmospheric Model Intercomparison Project (AMIP) experiment captures the climatology and the drying trend in recent decades. The fully coupled models from the CMIP5 historical experiment, however, have systematic errors in simulating the East African precipitation climatology by underestimating the long rains while overestimating the short rains. The multimodel mean of the historical simulations of the long rains anomalies, which is the best estimate of the radiatively forced change, shows a weak wetting trend associated with anthropogenic forcing. The SST anomaly pattern associated with the long rains has large discrepancies with the observations. The results herein suggest caution in projections of East African precipitation from CMIP5 or the relationship between the East African precipitation and the SST spatial pattern found in paleoclimate studies with coupled climate models.
The intertropical convergence zone (ITCZ) in the east Pacific is located north of the equator during most of the year. In daily data it is most variable in March–April when it may be located north of ...the equator (nITCZ), on both sides of the equator (dITCZ), or south of the equator (sITCZ), or it may be absent (when convection does not take on a zonally elongated form). Additionally, in strong El Niño years it is located on the equator during the boreal winter half-year. Here the focus is on conditions when the ITCZ has a presence south of the equator (dITCZ, sITCZ) and composites of various fields are compared to “normal conditions” i.e., when the ITCZ is north of the equator (nITCZ). Composites of sea surface temperature (SST), precipitation, outgoing longwave radiation, and the upper-level circulation show very similar patterns for dITCZ and sITCZ days, where the latter cases have almost double the amplitude of the former. The sITCZ state is viewed as an extreme case of the dITCZ state. Both are found to be related to the central Pacific (CP) La Niña with anomalous positive SST and atmospheric heating over the western tropical Pacific and anomalous negative SST and cooling over the central tropical Pacific. Ocean–atmosphere interaction plays an important role in developing the dITCZ and sITCZ anomalies. These daily composite patterns can be reproduced by the regression of monthly fields on the cold CP El Niño–Southern Oscillation mode, suggesting that the interannual rather than day-to-day variability dominates in contributing to the patterns of the composites.
A diagnostic framework is developed to explain the response of tropical cyclones (TCs) to climate in high-resolution global atmospheric models having different complexity of boundary conditions. The ...framework uses vortex dynamics to identify the large-scale control on the evolution of TC precursors—first non-rotating convective clusters and then weakly rotating seeds. In experiments with perturbed sea surface temperature (SST) and
CO
2
concentration from the historical values, the response of TCs follows the response of seeds. The distribution of seeds is explained by the distribution of the non-rotating convective clusters multiplied by a probability that they transition to seeds. The distribution of convective clusters is constrained by the large-scale vertical velocity and is verified in aquaplanet experiments with shifting Inter tropical Convergence Zones. The probability of transition to seeds is constrained by the large-scale vorticity via an analytical function, representing the relative importance between vortex stretching and vorticity advection, and is verified in aquaplanet experiments with uniform SST. The consistency between seed and TC responses breaks down substantially when the realistic SST is perturbed such that the spatial gradient is significantly enhanced or reduced. In such cases, the difference between the responses is explained by a change in the ventilation index, which influences the fraction of seeds that develop into TCs. The proposed TC-climate relationship serves as a framework to explain the diversity of TC projection across models and forcing scenarios.
Abstract
Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an ...intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (
IRG1
). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3–IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field.
Cuproptosis, a novel copper-induced cell death pathway, is linked to mitochondrial respiration and mediated by protein lipoylation. The discovery of cuproptosis unfolds new areas of investigation, ...particularly in cancers. The present study aimed to explore the role of cuproptosis in colorectal cancer progression. The genetic alterations of cuproptosis in colon cancer were evaluated using a database. MTT assays, colony formation, and flow cytometry were used to examine the effect of elesclomol-Cu and 4-Octyl itaconate (4-OI) on colorectal cancer cell and oxaliplatin-resistant cell viability. The anti-tumor effect of elesclomol with 4-OI was verified in vivo assay. The results showed that FDX1, SDHB, DLAT, and DLST genes were more highly expressed in normal tissues than those in primary tumor tissues. Patients with high expressions of these genes in tumor tissues had a better prognosis. Using MTT assay and colony formation analysis, elesclomol-Cu pulse treatment showed significant inhibition of cell viability in HCT116, LoVo, and HCT116-R cells. In addition, flow cytometry revealed elesclomol-Cu significantly promoted apoptosis. Tetrathiomolybdate, a copper chelator, markedly inhibited cuproptosis. Subsequently, we found 2-deoxy-D-glucose, a glucose metabolism inhibitor, sensitized cuproptosis. Furthermore, galactose further promoted cuproptosis. Interestingly, 4-OI significantly enhanced cuproptosis which was irrelevant to ROS production, apoptosis, necroptosis, or pyroptosis pathways. Aerobic glycolysis was inhibited by 4-OI through GAPDH, one of the key enzymes of glycolysis, sensitizing cuproptosis. Meanwhile, FDX1 knockdown weakened the ability of 4-OI to promote cuproptosis. In vivo experiments, 4-OI with elesclomol-Cu showed better anti-tumor effects. These results indicated that elesclomol-Cu rapidly halted cell growth in colorectal cancer cells and oxaliplatin-resistant cell line. Importantly, we revealed that 4-OI inhibited aerobic glycolysis by targeting GAPDH to promote cuproptosis.
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•Inhibiting aerobic glycolysis promotes cuproptosis in colorectal cancer.•4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH.•4-Octyl itaconate promote cuproptosis in colorectal cancer.
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