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Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record’s length and temporal precision allow us to test the idea that insolation changes caused by the Earth’s precession drove the terminations of each of the last seven ice ages as well as the millennia-long intervals of reduced monsoon rainfall associated with each of the terminations. On the basis of our record’s timing, the terminations are separated by four or five precession cycles, supporting the idea that the ‘100,000-year’ ice age cycle is an average of discrete numbers of precession cycles. Furthermore, the suborbital component of monsoon rainfall variability exhibits power in both the precession and obliquity bands, and is nearly in anti-phase with summer boreal insolation. These observations indicate that insolation, in part, sets the pace of the occurrence of millennial-scale events, including those associated with terminations and ‘unfinished terminations’. Records of the Asian monsoon have been extended to 640,000 years ago, and confirm both that the 100,000-year ice age cycle results from integral numbers of precessional cycles and that insolation influences the pacing of major millennial-scale climate events. A 640,000-year record of the Asian monsoon Prior records of the Asian monsoon have revealed cyclic variations over hundreds of thousands of years, probably driven by variations in insolation caused by the precession of Earth's orbit. Hai Cheng and colleagues now provide a speleothem record from Chinese cave samples that extends earlier records to 640,000 years ago, close to the maximum age possible with uranium/thorium dating. This spectacular record confirms that the characteristic '100,000-year' ice age cycle corresponds to an integral number (four or five) of precession cycles, and that insolation influences millennial-scale variations in monsoon strength.

Full-depth reclamation with Portland cement (FDR-PC) is a pavement rehabilitation technology that has garnered significant attention and research interest due to its ability to fully utilize existing pavement materials in situ and address deep structural issues within the pavement. This paper evaluates the advantages of FDR-PC in terms of carbon emission compared to traditional asphalt pavement rehabilitation technologies. Firstly, under the same service life conditions, the structural configurations of asphalt pavements were designed using 3D-Move Analysis for three different technologies: removal and reconstruction, cold central plant recycling, and FDR-PC. Subsequently, carbon emission models were established based on the life cycle assessment (LCA) method and the construction processes, allowing for a comparison of carbon emissions and energy consumption among the three technologies. Finally, a sensitivity analysis was conducted to assess the impact of various factors on carbon emissions during the FDR-PC construction process. The results indicate that in terms of carbon emissions from the pavement base layer, FDR-PC accounts for 92% and 90% of those produced by removal and reconstruction and cold central plant recycling, respectively, while its energy consumption is 60% and 70% of the latter two technologies. Notably, during the transportation phase, FDR-PC demonstrates carbon emissions and energy consumption levels at merely 4% each compared to conventional removal and reconstruction, and 6% each relative to cold central plant recycling. The sensitivity analysis further reveals that the cement content is the most influential factor affecting the carbon emissions of FDR-PC.

In order to investigate the self-healing behavior of asphalt binder at the molecule scale, the self-healing models of neat and aged asphalt binder with different damage degrees were established by introducing a vacuum pad between two layers filled with asphalt molecules. With this model, the self-healing process was simulated at various healing conditions to reveal the effects of oxidative aging, damage degree and healing temperature on the self-healing property. In addition, self-healing efficiency was evaluated using the indexes representative of the characteristics of different self-healing stages. Our results show that the oxidative aging weakened the stacked structure of the asphalt binder and increased the healing activation energy barrier. The increasing damage degree extended the distance for particles to travel, thus prolonging the time required for the crack interfaces contacting with each other. The elevated temperature improved the molecular mobility by supplying more energy to the molecular system. Furthermore, the self-healing process was evaluated quantitatively by the density variation at the crack closing stage and the diffusion coefficient at the intrinsic healing stage. The duration of each stage was influenced by the oxidative aging, damage degree and healing temperature. The findings in this paper are helpful to reveal and evaluate the self-healing property of asphalt binder.

A large array of proxy records suggests that the “4.2 ka event” marks an approximately 300-year long period (∼3.9 to 4.2 ka) of major climate change across the globe. However, the climatic manifestation of this event, including its onset, duration, and termination, remains less clear in the Indian summer monsoon (ISM) domain. Here, we present new oxygen isotope (δ18O) data from a pair of speleothems (ML.1 and ML.2) from Mawmluh Cave, Meghalaya, India, that provide a high-resolution record of ISM variability during a period (∼3.78 and 4.44 ka) that fully encompasses the 4.2 ka event. The sub-annually to annually resolved ML.1 δ18O record is constrained by 18 230Th dates with an average dating error of ±13 years (2σ) and a resolution of ∼40 years, which allows us to characterize the ISM variability with unprecedented detail. The inferred pattern of ISM variability during the period contemporaneous with the 4.2 ka event shares broad similarities and key differences with the previous reconstructions of ISM from the Mawmluh Cave and other proxy records from the region. Our data suggest that the ISM intensity, in the context of the length of our record, abruptly decreased at ∼4.0 ka (∼±13 years), marking the onset of a multi-centennial period of relatively reduced ISM, which was punctuated by at least two multi-decadal droughts between ∼3.9 and 4.0 ka. The latter stands out in contrast with some previous proxy reconstructions of the ISM, in which the 4.2 ka event has been depicted as a singular multi-centennial drought.

The Younger Dryas (YD), arguably the most widely studied millennial-scale extreme climate event, was characterized by diverse hydroclimate shifts globally and severe cooling at high northern latitudes that abruptly punctuated the warming trend from the last glacial to the present interglacial. To date, a precise understanding of its trigger, propagation, and termination remains elusive. Here, we present speleothem oxygen-isotope data that, in concert with other proxy records, allow us to quantify the timing of the YD onset and termination at an unprecedented subcentennial temporal precision across the North Atlantic, Asian Monsoon-Westerlies, and South American Monsoon regions. Our analysis suggests that the onsets of YD in the North Atlantic (12,870 ± 30 B.P.) and the Asian Monsoon-Westerlies region are essentially synchronous within a few decades and lead the onset in Antarctica, implying a north-to-south climate signal propagation via both atmospheric (decadal-time scale) and oceanic (centennial-time scale) processes, similar to the Dansgaard–Oeschger events during the last glacial period. In contrast, the YD termination may have started first in Antarctica at ∼11,900 B.P., or perhaps even earlier in the western tropical Pacific, followed by the North Atlantic between ∼11,700 ± 40 and 11,610 ± 40 B.P. These observations suggest that the initial YD termination might have originated in the Southern Hemisphere and/or the tropical Pacific, indicating a Southern Hemisphere/tropics to North Atlantic–Asian Monsoon-Westerlies directionality of climatic recovery.

The ubiquitination status of RIPK1 is considered to be critical for cell fate determination. However, the in vivo role for RIPK1 ubiquitination remains undefined. Here we show that mice expressing RIPK1 K376R which is defective in RIPK1 ubiquitination die during embryogenesis. This lethality is fully rescued by concomitant deletion of Fadd and Ripk3 or Mlkl . Mechanistically, cells expressing RIPK1 K376R are more susceptible to TNF-α induced apoptosis and necroptosis with more complex II formation and increased RIPK1 activation, which is consistent with the observation that Ripk1 K376R/K376R lethality is effectively prevented by treatment of RIPK1 kinase inhibitor and is rescued by deletion of Tnfr1. However, Tnfr1 −/− Ripk1 K376R/K376R mice display systemic inflammation and die within 2 weeks. Significantly, this lethal inflammation is rescued by deletion of Ripk3 . Taken together, these findings reveal a critical role of Lys376-mediated ubiquitination of RIPK1 in suppressing RIPK1 kinase activity–dependent lethal pathways during embryogenesis and RIPK3-dependent inflammation postnatally. RIPK1 integrates signals that drive both NF-κB activation and cell death pathways. Here Zhang et al. generate RIPK1 knock-in mice lacking a major ubiquitination site and demonstrate that this modification is important to suppress cell death during embryogenesis and inflammation postnatally.

During glacial terminations, massive iceberg discharges and meltwater pulses in the North Atlantic triggered a shutdown of the Atlantic Meridional Overturning Circulation (AMOC). Speleothem calcium carbonate oxygen isotope records (δ 18 O Cc ) indicate that the collapse of the AMOC caused dramatic changes in the distribution and variability of the East Asian and Indian monsoon rainfall. However, the mechanisms linking changes in the intensity of the AMOC and Asian monsoon δ 18 O Cc are not fully understood. Part of the challenge arises from the fact that speleothem δ 18 O Cc depends on not only the δ 18 O of precipitation but also temperature and kinetic isotope effects. Here we quantitatively deconvolve these parameters affecting δ 18 O Cc by applying three geochemical techniques in speleothems covering the penultimate glacial termination. Our data suggest that the weakening of the AMOC during meltwater pulse 2A caused substantial cooling in East Asia and a shortening of the summer monsoon season, whereas the collapse of the AMOC during meltwater pulse 2B (133,000 years ago) also caused a dramatic decrease in the intensity of the Indian summer monsoon. These results reveal that the different modes of the AMOC produced distinct impacts on the monsoon system. The influence of meltwater pulse events on Asian monsoon systems varied in line with the degree of AMOC weakening, according to a multi-proxy analysis of speleothems from China covering the penultimate glacial termination.

Frozen water is the most widespread type of ice present in ice caves and forms ice stalagmites and stalactites as well as floor ice, which is often several meters thick. Organic macroremains are commonly rare in this type of cave ice, which makes it difficult to establish a chronology and severely limits the use of such ice deposits as paleoenvironmental archives. Here, the chronology of such ice deposits in the inner part of the glaciated Eisriesenwelt, one of the world’s largest ice caves located in the European Alps of Austria, is determined by a combination of radiocarbon and 230 Th dating of cryogenic calcite. The data suggest that this cave ice has formed over the last three millennia, with a marked increase in the average accumulation rate during the thirteenth century, coinciding with the onset of the Little Ice Age in the Alps. Data from a second site closer to the entrance suggests that large parts of this tourist cave were likely ice-free during the Medieval Warm Period and that a substantial part of the ice is probably a relic of the Little Ice Age. The current warming has already penetrated deeper into the cave than during the Medieval Warm Period, although air exchange during the warm season is restricted by a door at the cave entrance.

Neutrophil extracellular traps (NETs) and immunity play critical roles in liver hepatocellular carcinoma (LIHC) progression, but their mechanisms remain unclear. This study explored the potential of NETs-related genes (NETs-RGs) and immune-related genes (IRGs) as prognostic markers for LIHC. LIHC transcriptome data and IRGs were obtained from public databases, and NETs-RGs were derived from prior research. Differentially expressed genes (DEGs) intersecting with key module genes were identified, followed by Cox regression analysis and machine learning to determine prognostic genes. A risk prediction model and nomogram were constructed and validated. Enrichment analysis, immune infiltration, and drug sensitivity studies were conducted to explore underlying mechanisms. Reverse transcription quantitative PCR (RT-qPCR) was used to validate findings. Five prognostic genes— HMOX1 , MMP9 , TNFRSF4 , MMP12 , and FLT3 —were identified. A risk model and nomogram demonstrated strong predictive ability. Gene set enrichment analysis revealed pathways related to retinol metabolism and cytochrome P450 drug metabolism in different risk groups. Immune infiltration analysis showed regulatory T cells positively correlated with MDSCs, which were directly associated with the five genes. Drug sensitivity analysis identified 74 drugs with differential sensitivity between risk groups; axitinib showed lower sensitivity in high-risk patients, while ABT-888 showed higher sensitivity. RT-qPCR confirmed reduced HMOX1 and FLT3 expression in LIHC tissues, while MMP9 and TNFRSF4 were upregulated. This study developed a robust predictive model for LIHC prognosis, offering valuable insights for clinical management and personalized treatment strategies.

The Indian summer monsoon (ISM) monsoon is critical to billions of people living in the region. Yet, significant debates remain on primary ISM drivers on millennial-orbital timescales. Here, we use speleothem oxygen isotope (δ 18 O) data from Bittoo cave, Northern India to reconstruct ISM variability over the past 280,000 years. We find strong coherence between North Indian and Chinese speleothem δ 18 O records from the East Asian monsoon domain, suggesting that both Asian monsoon subsystems exhibit a coupled response to changes in Northern Hemisphere summer insolation (NHSI) without significant temporal lags, supporting the view that the tropical-subtropical monsoon variability is driven directly by precession-induced changes in NHSI. Comparisons of the North Indian record with both Antarctic ice core and sea-surface temperature records from the southern Indian Ocean over the last glacial period do not suggest a dominant role of Southern Hemisphere climate processes in regulating the ISM variability on millennial-orbital timescales.