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Marine cloud brightening (MCB) is the deliberate injection of aerosol particles into shallow marine clouds to increase their reflection of solar radiation and reduce the amount of energy absorbed by the climate system. From the physical science perspective, the consensus of a broad international group of scientists is that the viability of MCB will ultimately depend on whether observations and models can robustly assess the scale-up of local-to-global brightening in todays climate and identify strategies that will ensure an equitable geographical distribution of the benefits and risks associated with projected regional changes in temperature and precipitation. To address the physical science knowledge gaps required to assess the societal implications of MCB, we propose a substantial and targeted program of research-field and laboratory experiments, monitoring, and numerical modeling across a range of scales.

Abstract The switch from oxidative phosphorylation to glycolysis is crucial for microglial activation. Recent studies highlight that histone lactylation promotes macrophage homeostatic gene expression via transcriptional regulation, but its role in microglia activation in Parkinson’s disease (PD) remains unclear. Here, we demonstrated that inhibiting glycolysis with 2-deoxy-d-glucose alleviates microgliosis, neuroinflammation and dopaminergic neurons damage by reducing lactate accumulation in PD mice. Notably, we observed a marked increase in histone lactylation, particularly H3K9 lactylation, in microglia in the substantia nigra of PD mice. Mechanistically, CUT&Tag and Chip-qPCR analyses revealed that H3K9 lactylation enriched at the SLC7A11promoter and activated its expression. Importantly, inhibiting SLC7A11 by sulfasalazine mitigated microglia-mediated neuroinflammation and improved motor function in PD mice. Moreover, we found that lactate-induce histone lactylation is dependent on P300/CBP. Collectively, our findings demonstrate that glycolysis-derived lactate promotes microglial activation via histone lactylation and provide a potential therapeutic strategy for PD.

Abstract Background One of the main causes of health-related issues in children is neurodevelopmental disorders (NDDs), which include attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and Tourette syndrome (TS). Nonetheless, there is relatively little prior research looking at the link between immunological inflammation and NDDs. Our work uses a two-sample Mendelian Randomization (MR) approach to provide a thorough evaluation of the causal effects of immune traits on ADHD, ASD, and TS. Methods As exposures, 731 immunological traits’ genetic associations were chosen, and the outcomes were genome-wide association data for ADHD, ASD, and TS. The inverse-variance weighted (IVW), weighted median (WM), and MR-Egger methods were used to conduct MR analysis. The results’ robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity analysis. Results With single-nucleotide polymorphisms serving as instruments and false discovery rate (FDR) correction applied, the study found that significantly higher expression of CD62L on CD62L+ myeloid DC (IVW, OR: 0.926, 95% CI 0.896~0.958, P = 9.42 × 10–6, FDR = 0.007) and suggestively higher absolute cell count (AC) of CD28 + DN (CD4-CD8-) (IVW, OR: 0.852, 95% CI = 0.780 ∼ 0.932, P-value = 4.65 × 10−4, FDR = 0.170) was associated with a lower risk of ADHD. There was no pleiotropy, and the causal relationships were strong according to sensitivity, leave-one-out, and MR-Steiger directionality tests. For ASD and TS, no harmful or protective immune traits were observed. Conclusions The results of the study lend credence to the theory that deficiency in CD62L on CD62L+ myeloid DC and CD28 + DN (CD4-CD8) AC may contribute to the onset of ADHD.

With the increase in the proportion of renewable energy connected to the grid, a large number of N-1 security constraints should be considered in the security-constrained economic dispatch (SCED) to ensure the reliable operation of the power system, which causes a great computational burden. However, only a small number of constraints in the N-1 security constraints are contributing factors. Therefore, the elimination of redundant constraints can significantly improve the solution efficiency of the SCED model. First, a new SCED model considering wind power and photovoltaic is established, and a low-rank approximation (LRA) surrogate model is constructed based on the historical operation information of the SCED model. Then, the active constraints are identified based on the estimation results of the LRA surrogate model and the active constraint set is constructed. Next, an iterative solution process of the SCED model based on LRA surrogate model is proposed. Finally, the simulations are conducted on an IEEE 39-bus system. The simulation results show that the error between the solution results of the LRA surrogate and the SCED models is less than 10%, the active constraint identification accuracy is raised, and the average iterative solution time of the proposed solution process is reduced by more than 50%, which indicates the improvement of the solution efficiency of the SCED model.

The water cycle is an important component of the earth system and it plays a key role in many facets of society, including energy production, agriculture, and human health and safety. In this study, the Energy Exascale Earth System Model version 1 (E3SMv1) is run with low-resolution (roughly 110 km) and high-resolution (roughly 25 km) configurations—as established by the High Resolution Model Intercomparison Project protocol—to evaluate the atmospheric and terrestrial water budgets over the conterminous United States (CONUS) at the large watershed scale. The warm season water cycle slows down in the HR experiment relative to the LR, with decreasing fluxes of precipitation, evapotranspiration, atmospheric moisture convergence, and runoff. The reductions in these terms exacerbate biases for some watersheds, while reducing them in others. For example, precipitation biases are exacerbated at HR over the Eastern and Central CONUS watersheds, while precipitation biases are reduced at HR over the Western CONUS watersheds. The most pronounced changes with resolution to the water cycle come from reductions in precipitation and evapotranspiration. The reduction in evapotranspiration reduces the biases across nearly all of the CONUS. Additional exploratory metrics show improvements to water cycle extremes (both in precipitation and streamflow), fractional contributions of different storm types to total precipitation, and mountain snowpack.

Introduction RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure.Methods Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023.Results Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate.Conclusions Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

BackgroundAntioxidants from both supplements and diet have been suggested to potentially reduce oxidative stress in individuals with ADHD. However, there is a lack of studies utilizing the Mendelian randomization (MR) method to explore the relationship between dietary and supplemental antioxidants with ADHD.MethodsThis study employed two-sample mendelian randomization. Various specific antioxidant dietary supplements (such as coffee, green tea, herbal tea, standard tea, and red wine intake per week), along with diet-derived circulating antioxidants including Vitamin C (ascorbate), Vitamin E (α-tocopherol), Vitamin E (γ-tocopherol), carotene, Vitamin A (retinol), zinc, and selenium (N = 2,603–428,860), were linked to independent single nucleotide polymorphisms (SNPs). Data on ADHD was gathered from six sources, comprising 246,888 participants. The primary analytical method utilized was inverse variance weighting (IVW), with sensitivity analysis conducted to assess the robustness of the main findings.ResultsIn different diagnostic periods for ADHD, we found that only green tea intake among the antioxidants was significantly associated with a reduced risk of ADHD in males (OR: 0.977, CI: 0.963–0.990, p

This paper provides an overview of the United States (US) Department of Energy's (DOE's) Energy Exascale Earth System Model version 2 (E3SMv2) fully coupled regionally refined model (RRM) and documents the overall atmosphere, land, and river results from the Coupled Model Intercomparison Project 6 (CMIP6) DECK (Diagnosis, Evaluation, and Characterization of Klima) and historical simulations - a first-of-its-kind set of climate production simulations using RRM. The North American (NA) RRM (NARRM) is developed as the high-resolution configuration of E3SMv2 with the primary goal of more explicitly addressing DOE's mission needs regarding impacts to the US energy sector facing Earth system changes. The NARRM features finer horizontal resolution grids centered over NA, consisting of 25→100¯km atmosphere and land, a 0.125 river-routing model, and 14→60¯km ocean and sea ice. By design, the computational cost of NARRM is 1/43× of the uniform low-resolution (LR) model at 100¯km but only 1/4¯10¯%-20¯% of a globally uniform high-resolution model at 25¯km. A novel hybrid time step strategy for the atmosphere is key for NARRM to achieve improved climate simulation fidelity within the high-resolution patch without sacrificing the overall global performance. The global climate, including climatology, time series, sensitivity, and feedback, is confirmed to be largely identical between NARRM and LR as quantified with typical climate metrics. Over the refined NA area, NARRM is generally superior to LR, including for precipitation and clouds over the contiguous US (CONUS), summertime marine stratocumulus clouds off the coast of California, liquid and ice phase clouds near the North Pole region, extratropical cyclones, and spatial variability in land hydrological processes. The improvements over land are related to the better-resolved topography in NARRM, whereas those over ocean are attributable to the improved air-sea interactions with finer grids for both atmosphere and ocean and sea ice. Some features appear insensitive to the resolution change analyzed here, for instance the diurnal propagation of organized mesoscale convective systems over CONUS and the warm-season land-atmosphere coupling at the southern Great Plains. In summary, our study presents a realistically efficient approach to leverage the fully coupled RRM framework for a standard Earth system model release and high-resolution climate production simulations.

This work documents version two of the Department of Energy's Energy Exascale Earth System Model (E3SM). E3SMv2 is a significant evolution from its predecessor E3SMv1, resulting in a model that is nearly twice as fast and with a simulated climate that is improved in many metrics. We describe the physical climate model in its lower horizontal resolution configuration consisting of 110 km atmosphere, 165 km land, 0.5° river routing model, and an ocean and sea ice with mesh spacing varying between 60 km in the mid-latitudes and 30 km at the equator and poles. The model performance is evaluated with Coupled Model Intercomparison Project Phase 6 Diagnosis, Evaluation, and Characterization of Klima simulations augmented with historical simulations as well as simulations to evaluate impacts of different forcing agents. The simulated climate has many realistic features of the climate system, with notable improvements in clouds and precipitation compared to E3SMv1. E3SMv1 suffered from an excessively high equilibrium climate sensitivity (ECS) of 5.3 K. In E3SMv2, ECS is reduced to 4.0 K which is now within the plausible range based on a recent World Climate Research Program assessment. However, a number of important biases remain including a weak Atlantic Meridional Overturning Circulation, deficiencies in the characteristics and spectral distribution of tropical atmospheric variability, and a significant underestimation of the observed warming in the second half of the historical period. An analysis of single-forcing simulations indicates that correcting the historical temperature bias would require a substantial reduction in the magnitude of the aerosol-related forcing.