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Background Coral reefs are being increasingly threatened due to global climate change. However, some coral species have shown strong tolerance despite living in marginal environments. The species Pavona decussata from Weizhou Island in the South China Sea experiences subaerial exposure in summer and winter due to extreme low tides, and their environmental acclimatization to this aerial exposure remains unexplored. Results Here we aimed to explore the molecular mechanism of P. decussata under season or subaerial exposure background through physiological and multi-omics integrative analyses. Specifically, corals with a history of seasonal air exposure underwent comprehensive changes in energy metabolism and defense mechanisms compared to permanently submerged corals. In summer, corals experiencing subaerial exposure enhanced antioxidant defense by increasing the activities of the enzymes T-SOD and CAT, and the coral-associated bacterial community shifted toward the class Alphaproteobacteria that may have provided corals with resistance to environmental stresses. Moreover, the decrease in the transcript levels of the TCA cycle and the increase in metabolite content of ornithine suggested an alteration in energy metabolic pathways. Corals with an air-exposed background may have enhanced energy reserves in winter, as indicated by a higher content of Chl a and a rebound in coral-associated bacterial community toward the class Gammaproteobacteria. Furthermore, accumulation of the metabolite leukotriene D4 and activation of the TGF-beta signaling pathway suggested higher anti-inflammatory requirements and positive regulation by innate immunity. Conclusions This study provides insights into the acclimatization of P. decussata to seasonal environmental fluctuations and demonstrates that relatively high-latitude corals possess the plasticity and acclimatory capacity to adapt to marginal environments.

Paleoclimate research has built a framework for Earth’s climate changes over the past 65 million years or even longer. However, our knowledge of weather-timescale extreme events (WEEs, also named paleoweather), which usually occur over several days or hours, under different climate regimes is almost blank because current paleoclimatic records rarely provide information with temporal resolution shorter than monthly scale. Here we show that giant clam shells (Tridacna spp.) from the tropical western Pacific have clear daily growth bands, and several 2-y-long (from January 29, 2012 to December 9, 2013) daily to hourly resolution biological and geochemical records, including daily growth rate, hourly elements/Ca ratios, and fluorescence intensity, were obtained. We found that the pulsed changes of these ultrahigh-resolution proxy records clearly matched with the typical instrumental WEEs, for example, tropical cyclones during the summerautumn and cold surges during the winter. When a tropical cyclone passes through or approaches the sampling site, the growth rate of Tridacna shell decreases abruptly due to the bad weather. Meanwhile, enhanced vertical mixing brings nutrient-enriched subsurface water to the surface, resulting in a high Fe/Ca ratio and strong fluorescence intensity (induced by phytoplankton bloom) in the shell. Our results demonstrate that Tridacna shell has the potential to be used as an ultrahigh- resolution archive for paleoweather reconstructions. The fossil shells living in different geological times can be built as a Geological Weather Station network to lengthen the modern instrumental data and investigate the WEEs under various climate conditions.

Reconstructing past sea‐level changes is critical in Quaternary science. On remote oceanic reefs, aragonite‐to‐calcite alteration occurs during subaerial exposure, directly recording the timing of sea‐level fall. U–Th dating of coral calcite is challenging due to open‐system issues. However, following calcite formation, the accumulated thermoluminescence (TL) signal can date the initial subaerial exposure event. This study pioneers the application of isothermal thermoluminescence (ITL) dating of reef calcite from the Xisha Islands, South China Sea. ITL single‐aliquot regenerative‐dose protocol improved the precision of equivalent dose measurement. By integrating dose rate simulation within a Bayesian framework constrained by U–Th ages, we obtained ITL ages of 127.0 ± 8.0 and 138.5 ± 1.5 ka for two reef core samples, dating sea‐level lowstands to late Marine Isotope Stage 6. Our results demonstrate that ITL dating of reef calcite enables the high‐resolution chronostratigraphic reconstruction of sea‐level sequences back to at least 1.5 million years ago.

Coral skeleton δ13C is a routinely measured indicator in modern insolation change research, but the knowledge of environmental and climatic signals recorded in its seasonality during geological time is sparse. In this study, we present eight Porites coral δ13C records from the mid‐late Holocene to the present from the northern South China Sea (NSCS). Compared with the main control factors for modern δ13C changes, coral δ13C seasonality in the NSCS since the mid‐Holocene shows a long‐term decreasing trend, which is consistent with the change trend as orbital‐induced (precession) insolation seasonal amplitude. By excluding other influencing factors, we speculate that the stronger coral δ13C seasonality (18.8%) over the mid‐Holocene than modern period is attributable to the metabolic effect, which predicts the stronger coral δ13C seasonality under stronger insolation seasonality. Our study has implications for coral δ13C seasonality as a potential indicator to record past insolation information under different climatic backgrounds. Plain Language Summary Numerous studies have documented the seasonal features of fast‐growing modern coral skeleton δ13C in response to insolation variation. The environmental and climatic signals recorded by coral δ13C seasonality in the geological period remain unclear owing to the relatively short length of observation records. Here we present monthly resolved δ13C records in seven fossil Porites corals (5.6–3.6 ka BP, before 1950 CE) and one modern Porites coral (1987–2001 CE) from the northern South China Sea (NSCS). Compared with the widely accepted prevailing control factors for modern coral δ13C, our results indicated that the stronger coral δ13C seasonality (18.8%) over the mid‐Holocene compared to the modern period is consistent with the orbital‐induced (precession) insolation changes, which indicate a declining seasonality from the mid‐Holocene to present. By excluding other influencing factors, we infer that a tendency toward higher δ13C seasonality during the mid‐Holocene was primarily driven by the metabolic fractionation caused by the enhanced insolation seasonality. This study highlighted coral δ13C seasonality as a potential indicator for recording past insolation information. Key Points The seasonal variation of modern coral skeleton δ13C in the northern South China Sea (NSCS) is primarily controlled by solar insolation Coral δ13C seasonality in the NSCS since the mid‐Holocene shows a long‐term decreasing trend The decrease of orbital‐induced (precession) insolation seasonal amplitude led to the declining trend of δ13C seasonality

This paper reviews both the recent and longer-term （Holocene） ecological history of coral reefs in the South China Sea （SCS）. （1） Local ecological monitoring since the 1960s shows that the coral reefs in the South China Sea have declined dramatically, reflecting the rapid decrease of living coral cover and the great loss of symbiotic zooxanthellae. Collectively, this has led to a significant decrease of annual CaCO3 production. Heavy anthropogenic activities and global warming are recognized as major triggers of the observed coral reef degradation. Observations show that the modern coral reefs in the SCS are a source of at- mospheric CO2 in summer. （2） Coral reefs of the SCS have been widely used to reveal longer-term environmental variations, including Holocene high-resolution sea surface temperature （SST） and abrupt climate events, millennial-scale E1 Nifio varia- tions, millennial- and centennial-scale sea level oscillations, strong and cyclic storm activities, East Asian monsoon intensities, variation in seawater pH, and recent seawater pollution. （3） Coral reefs of the southern SCS have experienced repeated epi- sodes of bleaching over the last 200 years due to high SST and intense E1 Nino events; coral reefs of the northern SCS suffered high levels of mortality during several abrupt winter cold-water bleaching events during the middle Holocene warm period. On average, recovery after the middle Holocene cold-bleaching took 20-30 years; recovery following other middle Holocene en- vironmental stresses took approximately 10-20 years. Such findings have significantly contributed to the understanding of the present ecological pressures faced by the coral reefs in the SCS, the histories of Holocene climate/environment changes, and the long-term models of coral reef responses to various past environmental changes.

Objective: To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Methods: Electronic databases including Pubmed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) related to high-grade gliomas. The inclusion of qualified literature and extraction of data were conducted by two independent reviewers. The primary clinical outcome measures of network meta-analysis were overall survival (OS) while progression-free survival (PFS), objective response rate (ORR) and adverse event of grade 3 or higher were secondary measures. Results: 22 eligible trials were included in the systematic review, involving 3423 patients and 30 treatment regimens. Network meta-analysis included 11 treatments of 10 trials for OS and PFS, 10 treatments of 8 trials for ORR, and 8 treatments of 7 trials for adverse event grade 3 or higher. Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21–0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16–0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21–0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21–0.74), bevacizumab plus lomustine (90 mg/m 2 ) (HR, 0.53; 95%CI, 0.33–0.84), bevacizumab plus lomustine (110 mg/m 2 ) (HR, 0.21; 95%CI, 0.06–0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18–0.99), lomustine (HR, 0.5; 95%CI, 0.33–0.76), and nivolumab (HR, 0.38; 95%CI, 0.19–0.73). For PFS, only the hazard ratio between bevacizumab plus vorinostat and bevacizumab plus lomustine (90 mg/m 2 ) was significant (HR,0.51; 95%CI, 0.27–0.95). Lomustine and nivolumab conferred worse ORR. Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst. Conclusion: The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m 2 ) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.

Multiple sclerosis (MS) represents a multifaceted autoimmune ailment, prompting the development and widespread utilization of numerous therapeutic interventions. However, extant medications for MS have proven inadequate in mitigating relapses and halting disease progression. Innovative drug targets for preventing multiple sclerosis are still required. The objective of this study is to discover novel therapeutic targets for MS by integrating single-cell transcriptomics and Mendelian randomization analysis. The study integrated MS genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data for analysis and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and MS. Sequential analyses involving colocalization and Phenome-wide association studies (PheWAS) were conducted to validate the causal role of candidate genes. Following stringent quality control preprocessing of scRNA-seq data, 1,123 expression changes across seven peripheral cell types were identified. Among the seven most prevalent cell types, 97 genes exhibiting at least one eQTL were discerned. Examination of MR associations between 28 proteins with available index pQTL signals and the risk of MS outcomes was conducted. Co-localization analyses and PheWAS indicated that FCRL3 may exert influence on MS. The integration of scRNA-seq and MR analysis facilitated the identification of potential therapeutic targets for MS. Notably, FCRL3, implicated in immune function, emerged as a significant drug target in the deCODE databases. This research underscores the importance of FCRL3 in MS therapy and advocates for further investigation and clinical trials targeting FCRL3.

Cadmium (Cd) geochemical cycle plays a significant role in the composition and function of the marine ecosystem. Skeletal cadmium‐to‐calcium (Cd/Ca) ratios in hermatypic corals have been applied to reconstruct the historical changes of oceanic and climatic processes, yet there was no systematic evaluation of this tracer's natural variability in high resolution over time. Here, we reported a coral skeletal Cd/Ca record in monthly resolution from 1999 to 2008 CE and reconstructed the history of Cd contents in surface seawater in the northern South China Sea. A significant seasonal variation (higher in the winter but lower in the summer) of Cd contents in surface seawater can be identified. We found that the seasonal variations in coral skeletal Cd/Ca ratios exhibited significant trends coupled with the surface wind speeds, indicating that strong winds had likely driven the vertical seawater mixing process and then induced the process of sediment remobilization on the shelf, which significantly increased Cd contents in surface seawater. The reduction in Cd contents in surface seawater due to biological processes might be masked by the impacts of surface winds. Importantly, we also observed that coral skeletal Cd/Ca records in the winter showed significant correlations with the winter monsoon index, highlighting the possibility as a new proxy of winter monsoon in the non‐upwelling shelf environments. Plain Language Summary Cadmium (Cd) is a nutrient element absorbed by phytoplankton in surface seawater, showing a distribution of low surface content and high bottom content. In order to determine the seasonal variations of Cd content in surface seawater in the northern South China Sea, we analyzed the coral skeletal Cd/Ca ratios in monthly resolution (1999–2008 CE) and finally concluded that the process of sediment resuspension and vertical mixing of seawater driven by winter monsoons is the main reason. The reduction of Cd contents in surface seawater due to biological processes was masked by the impacts of surface winds. In the past, Cd content in seawater/coral has been used to track the history of upwelling and El Niño Southern Oscillation, but the potential indicative on winter monsoon has not been reported so far. Considering that the trend between coral skeletal Cd/Ca ratios and average wind speeds showed a great agreement, we suggested that coral skeletal Cd/Ca ratios in the winter might be a potential proxy of winter monsoon. Key Points Coral skeletal Cd/Ca ratios in monthly resolution were first reported Seawater mixing process and sediments resuspension caused by winter monsoon are responsible for Cd seasonal variations in surface seawater Coral skeletal Cd/Ca ratios have potential to be a novel proxy for winter monsoon

Extreme sea surface temperature (SST) events, such as marine heatwaves (MHWs) and marine cold spells (MCSs), severely affect warm water coral reefs. However, further study is required on their historical and future spatiotemporal patterns, driving mechanisms, and impacts in coral reef regions. This study analyzed the spatiotemporal patterns in MHWs/MCSs for the periods 1982–2022 and 2023–2070 using ten indices based on OISSTv2.1 and CMIP6 data, respectively, identified key MHW drivers via four machine learning methods (Random Forest, Extreme Gradient Boosting, Light Gradient Boosting Machine, and categorical boosting) and SHAP values (Shapley Additive Explanations), and then examined their relationship with coral coverage across ten global marine regions. Our results revealed that (1) MHWs are not only increasing in their average intensity but also becoming more extreme, while MCSs have declined. More MHW days are observed in regions like the Red Sea, the Persian Gulf, and the South Pacific Islands, with increases of up to 28 days per decade. (2) Higher-latitude coral reefs are experiencing more severe MHWs than equatorial regions, with up to 1.24 times more MHW days, emphasizing the urgent need to protect coral refuges. (3) MHWs are projected to occur nearly year-round by 2070 under scenario SSP5–8.5. The area ratio of MHWs to MCSs is expected to rise sharply from 2040 onward, reaching approximately 100-fold under the SSP2–4.5 scenario and 196-fold under the SSP5–8.5 scenario, particularly in the Marshall Islands and Caribbean Sea regions. (4) The coefficient of variation (CV) of annual temperature, annual ocean heat content, and monthly temperature were the top three factors driving MHW intensity. We emphasize that future MHW predictions should focus more on the CV of forecasting indicators rather than just the climate means. (5) Coral coverage exhibited post-mortality processes following MHWs, showing a strong negative correlation (r = −0.54, p < 0.01) with MHWs while demonstrating a significant positive correlation (r = 0.6, p < 0.01) with MCSs. Our research underscores the sustained efforts to protect and restore coral reefs amid escalating climate-induced stressors.

As one of the micro-blocks dispersed in the South China Sea (SCS), the basement of the Xisha Islands has rarely been drilled because of the thick overlying Cenozoic sediments, which has led to a confused understanding of the pre-Cenozoic basement of the Xisha Islands. Well CK-1, a kilometer-scale major scientific drill in the Xisha Islands in the northwestern SCS, penetrated thick reefal limestone (0–888.4 m) and the underlying basement rocks (888.4–901.4 m). In this study, we present the zircon U-Pb ages of basement basaltic pyroclastic rocks from Well CK-1 in the Xisha Islands of the northwestern SCS to investigate the basement nature of the Xisha micro-block. The basement of Well CK-1 consists of basaltic pyroclastic rocks on the seamount. The zircon grains yielded apparent ages ranging from ca. 2 138.9 Ma to ca. 36 Ma. The old group of zircon grains from Well CK-1 was considered to be inherited zircons. Two Cenozoic zircons gave a weighted mean 206 pb/ 238 U age of (36.3 ± 1.1) Ma, Mean Squared Weighted Deviations (MSWD) = 1.2, which may represent the maximum age of the volcano eruption. The Yanshanian inherited zircons (116.9–105.7 Ma and 146.1–130.2 Ma) from Well CK-1 are consistent with the zircons from Well XK-1, indicating that the basement of Chenhang Island may be similar to that of Well XK-1. We propose that the Xisha micro-block may have developed on a uniform Late Jurassic metamorphic crystalline basement, intruded by Cretaceous granitic magma.