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The Aqishan-Caixiashan polymetallic ore cluster, located in the eastern Tianshan Orogenic Belt, is part of the southern Central Asian Orogenic Belt (CAOB) and experienced extensive tectono-magmatic events with polymetallic mineralization during the Carboniferous. However, the Carboniferous tectonic affinity and magmatic evolution of the ore cluster are still controversial, which limits further understanding of the tectonic evolution and regional metallogeny. With the aim of solving these problems, we have carried out geochronological and geochemical studies on Carboniferous intrusive rocks and volcanic rocks from the ore cluster. The samples of the Carboniferous magmatic rocks are enriched in LREEs and LILEs but depleted in HFSEs, which attest to the I-type affinity and are similar to those formed in a continental arc. The early Carboniferous granodiorites and granites (350–343 Ma) in the Central Tianshan Block (CTB), with high Mg# values of 37–66, low Y values of 2.3–17.2 ppm, and high Sr/Y ratios (34–85), show characteristics of adakites that are formed by partial melting of delaminated oceanic crust and/or lower crust. Additionally, they have a wide range of εHf(t) values (5.4–15.9), high εNd (t) values (1.78–6.31) and low I Sr values (0.705–0.706), indicating a mixed source of depleted mantle and lower crust for its origin. The Late Carboniferous volcanic rocks (314–306 Ma) in the Aqishan-Yamansu Tectonic Belt (AYTB) north of the CTB have obviously negative Nb–Ta-Ti anomalies, as well as high Y contents (12–20 ppm) and low Sr/Y ratios (5.6–29.9) compared to primitive mantle, which has a relatively flat chondrite-normalized REE pattern, resembling arc-related magmas. Additionaly, they have positive values of εHf(t) values (8.7–14.7), high εNd(t) values (3.04–4.45) and low I Sr ratios (0.704–0.707), showing a depleted mantle source, which is weakly affected by the contamination of ancient crustal material. Combining this study and previous works, we suggest that the continuous southwards subduction of the North Tianshan Ocean during the Carboniferous generated the continental arc and forearc basin in the northern part of the CTB. The expansion of the Aqishan-Yamansu forearc basin formed intrusions and volcanic formations along the arc belt. The early Carboniferous intermediate-felsic mantle-derived adakitic magmas in the CTB are probably related to regional Zn-Pb enrichment and mineralization, and the Late Carboniferous intrusions and volcanic formations in the AYTB are related to large-scale Fe-Cu-Zn-Pb-Ag mineralization. Graphical Abstract

The giant Changba-Lijiagou (Ch-L) Pb-Zn deposit is in the northeast part of the Xicheng ore cluster, Western Qinling Orogen. The ore genesis remains controversial; it could be either a sedimentary exhalative genetic type or an epigenetic hydrothermal genetic type. Here, in situ titanite U-Pb dating for the two kinds of titanite is presented, yielding ages of 212.8 ± 3.0 Ma in the mineralized skarn ore and 214.6 ± 5.1 Ma in the host rock. These ages conform to the previously reported magmatic zircon age (229–211 Ma) based on the in situ zircon U-Pb dating of plutons in this district and the time of large-scale magmatic–hydrothermal activities in Western Qinling Orogen (229–209 Ma). Titanites occurring in mineralized skarn and those that are calcite-hosted are similar to hydrothermal-origin titanites in major element characteristics. The Eu anomalies in the two types of titanite record oxidizing conditions during the mineralization process. A mineral assemblage of garnet, pyroxene, riebeckite, biotite, and potash feldspar, replacing the albite, is well-developed in the deposit. The mineralogical and geochronological characteristics indicate that the Ch-L Pb-Zn deposit is a distal skarn deposit and the result of intensive tectonomagmatic processes in the Xicheng ore cluster during the process of the Late Triassic orogeny.

The large Dongtangzi Zn-Pb deposit is located in the southwest of the Fengxian–Taibai (abbreviated as Fengtai) ore cluster in the west Qinling orogen. The origin of the deposit is controversial, positing diverse genesis mechanisms such as sedimentary-exhalative (SEDEX), sedimentary-reformed, and epigenetic-hydrothermal types. This study combines systematic ore geology observations with high-precision Rb-Sr and Sm-Nd ages of 211 Ma and in situ S-Pb isotopes to constrain the timing and origin of mineralization. In situ S-Pb isotopic studies show that the sulfide ores display a narrow range of δ34S values from 1.1‰ to 10.2‰, with 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of 18.07 to 18.27, 15.64 to 15.66, and 38.22 to 38.76, respectively. On the other hand, pyrites of the sedimentary period and the granite porphyry dike have δ34S values ranging from 15.8 to 21.4‰ and from 2.1 to 4.3‰ (with 206Pb/204Pb ratios of 18.09 to 18.10, 207Pb/204Pb ratios of 15.59 to 15.61, and 208Pb/204Pb ratios of 38.17 to 38.24), respectively. The above-mentioned S-Pb isotopic compositions indicate that the metallic materials involved in ore formation originated from a mixture of Triassic magmatic hydrothermal fluid and metamorphic basement. By integrating the regional geology, mineralization ages, and S-Pb isotopic studies, we propose that the Dongtangzi Zn-Pb deposit is the product of epigenetic hydrothermal fluid processes, driven by Late Triassic regional tectono-magmatic processes.

Mammalian interleukin (IL)-2 is a cytokine centrally involved in the differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells and in activation of cytotoxic effector lymphocytes. In bony fish, orthologs have been identified with an additional divergent gene on the same locus present in several fish species. We report here two divergent paralogs, and , in salmonids that originated from the whole genome duplication event in this fish lineage. The salmonid paralogs differ not only in sequence but also in exon sizes. The IL-2 isoforms that are encoded have disparate pI values and may have evolved to preferentially bind specific IL-2 receptors. Rainbow trout paralogs are highly expressed in thymus, spleen, gills, kidney and intestine, important tissues/organs in fish T cell development and function. Their expression in peripheral blood leukocytes (PBL) is low constitutively but can be upregulated by the mixed leukocyte reaction, by the T cell mitogen phytohemagglutinin and by signal mimics of T cell activation (phorbol 12-myristate 13-acetate and calcium ionophore). Both trout IL-2 isoforms promoted PBL proliferation and sustained high-level expression of and , suggesting that trout IL-2 isoforms are T cell growth/survival factors mainly expressed by activated T cells. The recombinant proteins for these two trout paralogs have been produced in and possess shared but also distinct bioactivities. IL-2A, but not IL-2B, induced and expression in PBL. IL-2B had a stronger effect on upregulation of the T helper 1 (Th1) cytokine ( ) and could sustain and expression levels. Nevertheless, both cytokines upregulated key Th1 ( and ) and T helper 2 (Th2) cytokines ( and ), cytokine and chemokine receptors and the antimicrobial peptide but had limited effects on T helper 17 cytokines and in PBL. They could also enhance PBL phagocytosis. These results suggest, for the first time in fish, that IL-2 isoforms may have an important role in regulating Th1 and Th2 cell development, and innate and adaptive host defenses in fish, and shed light on lineage-specific expansion, evolution, and functional diversification of in vertebrates.

Interferon regulatory factors (IRFs) are crucial regulators in initiating the host innate immune response against pathogen invasions. Dabry's sturgeon (Acipenser dabryanus) is particularly a valuable fish species found in the Yangtze River, China for which there is scarce immunological data. In the present study, we investigated the expression profile of sturgeon IRF genes. All adIRFs were composed of 8 exons and 7 introns, except adIRF1, which possessed 9 exons interrupted by 8 introns. Moreover, the predicted protein sequence has a DNA-binding domain (DBD) sharing high identity with spotted gar (Lepisosteus oculatus). Regarding the expression patterns, 5 adIRF genes were found to be constitutively expressed in all tissues examined, and were significantly higher in lymphoid organs (eg, blood, kidney, intestine, and spleen). Following Aeromonas hydrophila infection, the expression of adIRF1 and adIRF3 were upregulated in the spleen and caudal kidney, while both the adIRF5 and adIRF8 genes were downregulated in caudal kidney. In addition, adIRF4 was significantly upregulated at 3 h postinfection by A. hydrophila in the spleen and caudal kidney. These results suggest that adIRFs are related to the immune response to bacterial infection, which will help clarify the function of these IRFs and provide a fundamental basis for protecting the Dabry's sturgeon.

Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline‐recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN‐HF) were enrolled to assess the all‐cause mortality, HF mortality, all‐cause re‐hospitalization, and HF re‐hospitalization associated with digoxin use. Eight hundred eighty‐two eligible HFrEF patients in the CN‐HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow‐up of 28.6 months. Kaplan–Meier survival analysis showed that the all‐cause mortality (P < 0.001) and all‐cause re‐hospitalization (P = 0.020) were significantly higher in digoxin group than non‐digoxin group, while HF mortality (P = 0.232) and HF re‐hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional‐hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all‐cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27–2.44; P = 0.001] and all‐cause re‐hospitalization (HR 1.27; 95% CI 1.03–1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all‐cause mortality irrespective of rhythm or in combination with other guideline‐recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all‐cause mortality and all‐cause re‐hospitalization in HFrEF patients.