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To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg−1) and BUT-treated (1.75, 1.5 and 1.25 g kg−1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

Based on the approach of left and right kernel smoothing with unilateral kernel function, we, in this paper, define estimators of change point and jump size in nonparametric regression model with response missing at random. It is shown that the change point estimator is n-consistent and converges to the smallest maximizer of one-dimensional bilateral compound Poisson process, the jump size estimator is asymptotically normal. A simulation study is conducted to investigate the finite sample behavior for the proposed methods. [ABSTRACT FROM AUTHOR]

The petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF). To evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses. Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety. The PET LD50 was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect. These findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application. [ABSTRACT FROM AUTHOR]

In this paper, we focus on the left-truncated and right-censored model, and construct the local linear and Nadaraya-Watson type estimators of the conditional density. Under suitable conditions, we establish the asymptotic normality of the proposed estimators when the observations are assumed to be a stationary α-mixing sequence. Finite sample behavior of the estimators is investigated via simulations too. [ABSTRACT FROM AUTHOR]

Several large Ag‐polymetallic deposits have been newly discovered in the eastern segment of the East Kunlun Orogen, with the largest one being the high‐grade Nagengkangqieergou deposit (3,017 tons Ag at 310.04 g/t). The Ag ore veins are hosted in the Palaeoproterozoic Jinshuikou Group and Upper Triassic Elashan Formation, principally along NW‐trending faults and volcanogenic ring fractures. Alteration and mineralization processes occurred in two periods (J and E), which are hosted in two different ore‐bearing sequences (Jinshuikou Group and Elashan Formation respectively). These two periods can be subdivided into Stages J‐I, J‐II, J‐III, and J‐IV and Stages E‐I, E‐II, and E‐III. Fluid inclusions in the ore‐bearing quartz and calcite comprise predominantly of vapour‐rich two‐phase (vapour + liquid) type and minor pure‐liquid type. Fluid inclusions in Stage J quartz and calcite homogenized mainly at 270–330°C, 250–310°C, 250–290°C, and 170–250°C, with salinities of 5–6 wt.%, 4–6 wt.%, 4–5 wt.%, and 3–5 wt.% NaCl equiv., respectively. Fluid inclusions in Stage E quartz homogenized mainly at 210–250°C, 170–230°C, and 150–170°C, with salinities of 6–7 wt.%, 4–5 wt.%, and 1–2 wt.% NaCl equiv., respectively. δ13C and δ18OSMOW values of the calcite samples are of −6.0‰ to −2.8‰ and 5.2‰ to 20.5‰, respectively. The results indicate a mantle‐derived magmatic source and low temperature alteration. and δDV–SMOW values of the quartz and calcite from the Jinshuikou Group vary from −1.9‰ to 9.0‰ and −116.5‰ to −69.3‰, respectively, whilst those of δ18OH2O quartz from the Elashan Formation vary from −11.6‰ to 7.8‰ and −99.7‰ to −86.7‰. The results indicate that the ore‐forming fluids are of medium‐low temperatures and low salinities and were originated from magmatic water to meteoric water. Sulfide δ34SV–CDT values of the Jinshuikou Group and the Elashan Formation are of −6.1‰ to 0.8‰ and −3.4‰ to 0.9‰, respectively, suggesting a mantle‐derived magmatic source. Sulfide 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of the J‐period ores (18.190–18.622, 15.598–15.725, and 38.383–39.103, respectively) and E‐period ores (18.408–18.420, 15.746–15.758, and 38.879–38.895, respectively) are similar to those of granodiorite porphyry and Elashan Formation (sub)‐volcanic rocks, respectively, indicative of genetic connections between them. Integrating new evidence from fluid inclusions and C–H–O–S–Pb isotopes, we suggest that (a) mantle‐derived materials and their mixture with crust‐derived ones were critical to the ore formation, (b) the Nagengkangqieergou deposit was formed in a magmatic system and a (sub)‐volcanic system under the syn‐ and post‐collisional tectonics of the East Kunlun Orogen, respectively. [ABSTRACT FROM AUTHOR]

The seeds ofAmygdalus mongolicacontain various constituents including flavonoids and vitamin E, which are known to exert antioxidant effects. However, the safety of the oil extract of this compound is not fully known. The aim of this study was to determine the physicochemical properties ofA. mongolicaoil, identify the constituents and subsequently assess the effectiveness of utilizing this seed extract in hyperlipidemia as an antioxidant agent. In particular, the toxicity and safety ofA. mongolicaoil were examined with emphasis on effects on blood lipids level and serum lipid peroxidation using a hyperlipidemia rat model. Treatment with 20 ml/kgA. mongolicaoil produced no apparent adverse effects after 14 days in normal female and male rats. A dose of 2.5–10 ml/kgA. mongolicaoil administered to hyperlipidemic male rats significantly decreased serum total cholesterol (TC), low-density lipoprotein-C (LDL-C), malondialdehyde (MDA), total cholesterol high-density lipoprotein-C (TC/HDL-C), LDL-C/HDL-C, and atherosclerosis index(AI). In contrast, glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased. Data demonstrated thatA. mongolicaoil may be utilized in conditions of hyperlipidemia due to its antioxidant effects. [ABSTRACT FROM PUBLISHER]

Calc-alkaline andesitic rocks are a major product of subduction-related magmatism at convergent margins. Where these melts are originated, how long they are stored in the magma chambers, and how they evolved is still a matter of debate. In this study, we present new data of whole-rock elemental and Sr-Nd-Pb isotope compositions, and zircon U-Pb-Th isotopes and trace element contents of Nageng (basaltic-)andesites in the East Kunlun Orogen (NW China). The similar age and whole-rock elemental and Sr-Nd-Pb isotope contents suggest that the Nageng andesite and basaltic andesite are co-magmatic. Their low initial 87Sr/86Sr (0.7084–0.7086) but negative εNd(t) values (−10.61 to −9.49) are consistent with a magma source from the juvenile mafic lower crust, possibly related to the mantle wedge with recycled sediment input. The U-Pb age gap between the zircon core (ca. 248 Ma) and rim (ca. 240 Ma) reveals a protracted magma storage (~8 Myr) prior to the volcanic eruption. When compared to the zircon rims, the zircon cores have higher Ti content and Zr/Hf and Nb/Ta ratios, but lower Hf content and light/heavy rare earth element ratios, which suggests that the parental magma was hotter and less evolved than the basaltic andesite. The plagioclase accumulation likely resulted in Al2O3-enrichment and Fe-depletion, forming the calc-alkaline signature of the Nageng (basaltic-)andesites. The magma temperature, as indicated by the zircon saturation and Ti-in-zircon thermometry, remained low (725–828 °C), and allowed for the magma chamber to survive over ~8 Myr. The decreasing εHf(t) values from zircon core (avg. 0.21, range: −1.28 to 1.32) to rim (avg. −3.68, range: −7.30 to −1.13), together with the presence of some very old xenocrystic zircons (268–856 Ma), suggest that the magma chamber had undergone extensive crustal contamination. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1β, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

Amygdalus mongolica oil is rich in unsaturated fatty acids such as inoleic acid (47.11%) and oleic acid (23.81%). Our research demonstrates that it exerts a protective effect on rat models of pulmonary fibrosis, however, little is known regarding the underlying mechanism of action. This study aimed to characterize the therapeutic mechanism of action of A. mongolica oil on bleomycin-induced pulmonary fibrosis in rats. A. mongolica oil appears to regulate the levels of potential key serum biomarkers which include tetrahydrobiopterin, L-serine, citrulline and estradiol to participate in folate biosynthesis, glycine, serine and threonine metabolism, arginine biosynthesis and steroid hormone biosynthesis. And it also enriched intestinal microbial abundance, homogeneity and modulated the abundance of Duncaniell, Desulfovibrio , Peptococcaceae _unclassified , Dubosiella , Tyzzerella , Lachnospiraceae _NK4A136_group, Lactobacillus, Clostridiales_unclassified to exert a protective effect against pulmonary fibrosis. A. mongolica oil appears to confer protective effects against pulmonary fibrosis by affecting the level of pulmonary fibrosis metabolites and the abundance of related intestinal flora through multiple targets, as evidenced by our untargeted LC-MS/MS metabonomics evaluation and 16S rDNA sequencing technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zhou, Liu, Bai, Wang, Yang, Qiu, Chang and Shi.)

Renal fibrosis (RF) is a chronic and fatal disease related to the gradual deterioration of kidney function. MicroRNAs (miRNAs) play a key role in cellular functions and several of them related to the pathogenesis of RF have been identified, although the underlying mechanisms are unclear. In order to explore the miRNAs involved in RF progression, we established a model in rats by the unilateral ureteral ligation method. The animals were randomly divided into the control group, and the 2 week, 4 week and 6 week model groups. The indices of renal function were measured using routine biochemical assays. The differentially expressed miRNAs (DE-miRNAs) between the sham-operated and modelled rats were screened, and their putative target genes were identified using the miRanda software and functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The expression of transforming growth factor β1 (TGF-β1), Smad3 and Smad7 was confirmed by RT-PCR. Compared to the sham-operated group, the model groups showed a decrease in SOD activity, along with the increased renal coefficient, and higher MDA, HYP, Scr, BUN and ALB levels. In addition, TGF-β1, Smad3 and Smad7 were also upregulated in the RF groups. We identified 274 known and 11 novel DE-miRNAs in the 2 week, 114 known and 6 novel DE-miRNAs in the 4 week, and 41 known and 1 novel DE-miRNAs in the 6 week model groups. The putative target genes of these DE-miRNAs were enriched in metabolic processes, apoptosis, pyrimidine metabolism, and TNF and VEGF signalling pathways. Based on our findings, we surmise that miR-146a-3p, miR-148a-3p, miR-130a-5p, miR-362-3p and miR-122-5p are likely to be involved in the occurrence and development of RF, and miR-122-5p may play an inhibitory role. The underlying mechanisms need further investigation.