Supplemental Material: Strontium isotopes and rare earth elements in terrestrial hot-spring deposits: Characterization and geothermal implications

Data used in this study (Tables S1–S3). </p

Stable Carbon and Oxygen Isotopic Features of Banded Travertines from the Xiagei Fissure Ridge System (Shangri-La, China)

Banded travertines are important parts of fissure ridge systems, but studies on geochemical characterization of banded travertines are limited. This study investigated the lithofacies and stable carbon and oxygen isotopic features of banded travertines from Xiagei (southwestern China) to examine their formation mechanisms. Petrographic analyses of the banded travertines revealed two lithotypes: thick-laminated palisade crystalline crust and thin-laminated composite crystalline crust. δ13C and δ18O of the Xiagei banded travertines range from 2.82‰ to 4.50‰ V-PDB, and from −25.86‰ to −20.90‰ V-PDB. Parent CO2 evaluation shows that the Xiagei banded travertines mainly received CO2 from the decarbonation of marine carbonates, but the contributions of magmatic CO2 and the dissolution of marine carbonates are also unneglectable. Significantly, the magmatic-derived CO2 might indicate that the delamination of the lithosphere along with the asthenosphere upwelling could be taking place in the eastern Tibetan plateau. Paleotemperature calculation shows that the Xiagei travertines were precipitated from moderate- to high-temperature hot springs (44.3 to 86.8 °C). Interestingly, the thick-laminated palisade crystalline crust and thin-laminated composite crystalline crust display calculated paleotemperature between 66.6 and 86.8 °C and between 56.6 and 77.7 °C, respectively, reflecting the great role of water temperature in controlling the lithofacies of banded travertines. A comparison between the banded travertines at Xiagei and other areas also shows temperature is a non-negligible factor controlling banded travertine precipitation. However, this does not mean that water temperature is the decisive controlling factor and more studies on banded travertines are still indispensable to disclose the potential factors controlling the factors/processes affecting banded travertine lithofacies. This study provides a good example for understanding the relationship between lithofacies and stable isotopic geochemical characteristics of travertine deposits

Geochemical Characterization of Laminated Crystalline Crust Travertines Formed by Ca²⁺-Deficient Hot Springs at Sobcha (China)

Travertines formed of crystalline crust have been widely reported, but there has not been focus on their geochemical characteristics. We therefore carefully conducted a series of geochemical investigations and U-Th dating on a travertine mound mainly composed of crystalline crust from Sobcha (southwest China) to determine their geochemical features and geological implications. The Sobcha travertines dominantly consist of granular crystals and fan crystals and show δ13C from 3.4‰ to 4.9‰ V-PDB, δ18O from −26.7‰ to −23.7‰ V-PDB, and 87Sr/86Sr from 0.712458 to 0.712951. When normalized to PASS, the Sobcha travertines exhibit MREE enrichment relative to HREE and LREE, HREE enrichment relative to LREE, and positive Eu anomalies. The δ13C signatures and mother CO2 evaluation of the Sobcha travertines show that the Sobcha travertines were thermogene travertines largely receiving mother CO2 from (upper) mantle (i.e., magmatic CO2) or a mixture of soil-derived CO2 and CO2 related to carbonate decarbonation. The 87Sr/86Sr of the Sobcha travertines is out of the 87Sr/86Sr ranges of local deposits exposed at Sobcha and surrounding areas but is well matched with the mean 87Sr/86Sr of Nadi Kangri volcanic rocks which cropped out to the northeast of the studied travertines (over 20 km away). This might indicate the important role of the Nadi Kangri volcanic rocks in suppling Sr to the studied travertines, but more studies are required. The LREE depletion compared to MREE and HREE in the Sobcha travertines was interpreted to be caused by the difference in geochemical mobility between LREEs and HREEs during water–rock interaction at depth, while the MREE enrichment compared to HREE was considered to be most likely inherited from reservoir/aquifer rocks. The positive Eu anomalies of the Sobcha travertines may result from very high reservoir temperatures and/or preferential dissolution of Eu-rich minerals/rocks (especially plagioclase). The Sobcha travertine mounds displays no or very slight vertical variations in δ13C, 87Sr/86Sr, and REE patterns, indicating the compositional stability of mother CO2 and paleo-fluids. However, a significant vertical increase in δ18O was observed and was explained as the result of gradual water temperature decrease related to climate cooling, self-closure of the vents, or mound vertical growth. The findings in this study might help us better understand the deposition of crystalline crust in Ca2+-deficient hot spring systems

Fissure Ridges: A Reappraisal of Faulting and Travertine Deposition (Travitonics)

The mechanical discontinuities in the upper crust (i.e., faults and related fractures) lead to the uprising of geothermal fluids to the Earth’s surface. If fluids are enriched in Ca2+ and HCO3-, masses of CaCO3 (i.e., travertine deposits) can form mainly due to the CO2 leakage from the thermal waters. Among other things, fissure-ridge-type deposits are peculiar travertine bodies made of bedded carbonate that gently to steeply dip away from the apical part where a central fissure is located, corresponding to the fracture trace intersecting the substratum; these morpho-tectonic features are the most useful deposits for tectonic and paleoseismological investigation, as their development is contemporaneous with the activity of faults leading to the enhancement of permeability that serves to guarantee the circulation of fluids and their emergence. Therefore, the fissure ridge architecture sheds light on the interplay among fault activity, travertine deposition, and ridge evolution, providing key geo-chronologic constraints due to the fact that travertine can be dated by different radiometric methods. In recent years, studies dealing with travertine fissure ridges have been considerably improved to provide a large amount of information. In this paper, we report the state of the art of knowledge on this topic refining the literature data as well as adding original data, mainly focusing on the fissure ridge morphology, internal architecture, depositional facies, growth mechanisms, tectonic setting in which the fissure ridges develop, and advantages of using the fissure ridges for neotectonic and seismotectonic studies

Total Occlusion of the Culprit Artery in Non-ST-segment Elevation Acute Coronary Syndrome: an Analysis of the Influencing Factors and Long-term Outcome Following Percutaneous Coronary Intervention

Background About one-fourth of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are found with total occlusion of the culprit artery, and their outcomes are poor. However, there is little research in this population in China. Objective To identify the possible influencing factors of total occlusion of the culprit artery and long-term outcomes following percutaneous coronary interventions (PCI) in patients with NSTE-ACS. Methods Three hundred and seven NSTE-ACS patients with PCI treatment were recruited from the Third People&apos;s Hospital of Chengdu from January 2018 to December 2019, among whom, 42 with total occlusion of the culprit artery (pre-PCI TIMI grade 0 or 1, occlusion group) , and other 265 without (pre-PCI TIMI grade 2 or 3, non-occlusion group) . The baseline characteristics and results of regular follow-ups were collected. The endpoints were major adverse cardiac and cerebrovascular events (MACCE) , including all-cause death, recurrent myocardial infarction, revascularization, and new stroke. Multivariate Logistic regression was used to identify the potential influencing factors of total occlusion of the culprit artery. The Kaplan-Meier was used to estimate the cumulative incidence of MACCE. Multivariate Cox regression was adopted to assess the influence of total occlusion of the culprit artery on prognosis. Results Compared with non-occlusion group, occlusion group had higher prevalence of non-ST-segment elevation acute myocardial infarction and the left circumflex coronary artery as the culprit vessel, as well as higher levels of hypersensitive troponin T, creatine kinase isoenzyme and B-type natriuretic peptide at admission (P&lt;0.05) . Moreover, occlusion group had lower level of systolic blood pressure and left ventricular ejection fraction (LVEF) , as well as the left anterior descending coronary artery as the culprit vessel at admission (P&lt;0.05) . The results of multivariate Logistic regression analysis showed LVEF〔OR=1.064, 95%CI (1.018, 1.112) , P=0.006〕 was associated with total occlusion of the culprit artery in NSTE-ACS. Occlusion group had higher cumulative incidence of MACCE, revascularization or new stroke than non-occlusion group (P&lt;0.05) . After adjusting for confounding factors, multivariate Cox regression analysis revealed that total occlusion of the culprit artery was associated with MACCE〔OR=2.684, 95%CI (1.229, 5.862) , P=0.013〕 and revascularization〔OR=3.024, 95%CI (1.320, 6.931) , P=0.009〕 in NSTE-ACS. Conclusion LVEF may be an associated factor of total occlusion of the culprit artery in patients with NSTE-ACS. Therefore bedside echocardiography is recommended as a routine examination before coronary angiography in patients with NSTE-ACS. In addition, total occlusion of the culprit artery is an influencing factor of MACCE, revascularization, and new stroke in these patients

Sex-specific Analysis of the Management and Outcome of Elderly Patients with Acute Myocardial Infarction

Background There may be sex-specific differences in the treatment and outcome of elderly people with acute myocardial infarction (AMI) . However, few studies have reported sex-specific differences in management and prognosis of older Chinese people with AMI. Objective To assess the sex-specific differences in management strategies, in-hospital mortality and cardiovascular mortality within one year after discharge in older Chinese people with AMI. Methods We consecutively enrolled 1 579 elderly (&gt;60 years of age) patients with AMI admitted to 11 tertiary general hospitals in Chengdu between January 2017 and June 2019, including 1 056 men and 523 women. Sex-specific analysis of clinical characteristics, management strategies and 1-year outcome were performed. Kaplan-Meier estimator was used to describe the incidences of cardiovascular death within one year after discharge between men and women and the associated factors were explored using multivariate Cox proportions hazards regression analysis. Results Female patients had lower prevalence of smoking, and alcohol consumption, history of percutaneous coronary intervention and chronic obstructive pulmonary disease, typical symptoms including chest pain and chest tightness, and use of dual antiplatelet agents and statins, and lower mean creatinine levels than male patients (P&lt;0.05) . Moreover, female patients had older mean age, diabetes, and higher mean heart rate, greater prevalence of Killip class≥Ⅱ, and higher mean level of total cholesterol, longer mean symptom-onset-to-balloon time and first medical contact to balloon dilation time, and higher in-hospital mortality rate (P&lt;0.05) . Furthermore, the cardiovascular mortality rate within one year after discharge was higher in women (P&lt;0.05) . Multivariate Cox proportions hazards regression analysis showed sex〔HR=1.830, 95%CI (1.029, 3.255) , P=0.040〕, age〔HR=1.063, 95%CI (1.031, 1.095) , P&lt;0.001〕, ST-segment elevation myocardial infarction〔HR=2.382, 95%CI (1.380, 4.113) , P=0.002〕, cardiogenic shock〔HR=2.474, 95%CI (1.259, 4.859) , P=0.009〕, creatinine〔HR=1.004, 95%CI (1.001, 1.006) , P=0.003〕 and PCI〔HR=0.228, 95%CI (0.135, 0.386) , P&lt;0.001〕 were associated with cardiovascular death within one year after discharge. Conclusion The rates of reperfusion treatment in older women and men with AMI were similar, but there were differences in treatment efficiency and outcome. Older women with AMI had lower in-hospital treatment efficacy, longer total myocardial ischemia time, lower prevalence of pharmacological treatment, and higher in-hospital all-cause mortality and cardiovascular mortality within one year after discharge

Discovery of LLC0424 as a Potent and Selective <i>in Vivo</i> NSD2 PROTAC Degrader

Nuclear receptor-binding SET domain-containing 2 (NSD2), a methyltransferase that primarily installs the dimethyl mark on lysine 36 of histone 3 (H3K36me2), has been recognized as a promising therapeutic target against cancer. However, existing NSD2 inhibitors suffer from low activity or inferior selectivity, and none of them can simultaneously remove the methyltransferase activity and chromatin binding function of NSD2. Herein we report the discovery of a novel NSD2 degrader LLC0424 by leveraging the proteolysis-targeting chimera technology. LLC0424 potently degraded NSD2 protein with a DC50 value of 20 nM and a Dmax value of 96% in acute lymphoblastic leukemia (ALL) RPMI-8402 cells. Mechanistic studies revealed LLC0424 to selectively induce NSD2 degradation in a cereblon- and proteasome-dependent fashion. LLC0424 also caused continuous downregulation of H3K36me2 and growth inhibition of ALL cell lines with NSD2 mutation. Importantly, intravenous or intraperitoneal injection of LLC0424 showed potent NSD2 degradation in vivo

Discovery of LLC0424 as a Potent and Selective <i>in Vivo</i> NSD2 PROTAC Degrader

Nuclear receptor-binding SET domain-containing 2 (NSD2), a methyltransferase that primarily installs the dimethyl mark on lysine 36 of histone 3 (H3K36me2), has been recognized as a promising therapeutic target against cancer. However, existing NSD2 inhibitors suffer from low activity or inferior selectivity, and none of them can simultaneously remove the methyltransferase activity and chromatin binding function of NSD2. Herein we report the discovery of a novel NSD2 degrader LLC0424 by leveraging the proteolysis-targeting chimera technology. LLC0424 potently degraded NSD2 protein with a DC50 value of 20 nM and a Dmax value of 96% in acute lymphoblastic leukemia (ALL) RPMI-8402 cells. Mechanistic studies revealed LLC0424 to selectively induce NSD2 degradation in a cereblon- and proteasome-dependent fashion. LLC0424 also caused continuous downregulation of H3K36me2 and growth inhibition of ALL cell lines with NSD2 mutation. Importantly, intravenous or intraperitoneal injection of LLC0424 showed potent NSD2 degradation in vivo