Anti-thrombolytic effect of Salvia miltiorrhiza Bge extract in rats

Purpose: To study the effects of Salvia miltiorrhiza Bge. extract (SMBE) on thrombosis in rats.Methods: SMBE was obtained in water at 60 oC in an oven and then freeze-drying. Rats were divided into 6 groups of ten rats each: normal group, control group, reference group (aspirin 5 mg/kg) as well as three groups of SMBE groups (25, 50 and 100 mg/kg doses). Treatments were given orally once daily for 14 days. Common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6- keto-PGF1α) were measured in the rats.Results: Compared with control group, all doses of SMBE significantly and dose-dependently prolonged thrombosis occlusion time, reduced the weight of thrombus and increased the inhibition rate of thrombus (p < 0.01). Plasma TXB2 concentration of all SMBE groups decreased dose-dependently (p < 0.05) while that of 6-keto-PGF1α increased with decrease in extract dose (p < 0.05). There was association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all treatments, and also with occlusion time for SMBE treatment, but not for aspirin.Conclusion: The results demonstrate the anti-thrombosis effect of SMBE in rats. This finding suggests that the plant is a potential therapy for thrombosis.Keywords: Salvia miltiorrhiza Bge., Thrombosis, Thromboxane B2, 6-Keto-prostaglandin F1 alpha, Aspirin, Occlusion tim

mCL-NER: Cross-Lingual Named Entity Recognition via Multi-view Contrastive Learning

Cross-lingual named entity recognition (CrossNER) faces challenges stemming from uneven performance due to the scarcity of multilingual corpora, especially for non-English data. While prior efforts mainly focus on data-driven transfer methods, a significant aspect that has not been fully explored is aligning both semantic and token-level representations across diverse languages. In this paper, we propose Multi-view Contrastive Learning for Cross-lingual Named Entity Recognition (mCL-NER). Specifically, we reframe the CrossNER task into a problem of recognizing relationships between pairs of tokens. This approach taps into the inherent contextual nuances of token-to-token connections within entities, allowing us to align representations across different languages. A multi-view contrastive learning framework is introduced to encompass semantic contrasts between source, codeswitched, and target sentences, as well as contrasts among token-to-token relations. By enforcing agreement within both semantic and relational spaces, we minimize the gap between source sentences and their counterparts of both codeswitched and target sentences. This alignment extends to the relationships between diverse tokens, enhancing the projection of entities across languages. We further augment CrossNER by combining self-training with labeled source data and unlabeled target data. Our experiments on the XTREME benchmark, spanning 40 languages, demonstrate the superiority of mCL-NER over prior data-driven and model-based approaches. It achieves a substantial increase of nearly +2.0 $F_1$ scores across a broad spectrum and establishes itself as the new state-of-the-art performer.Comment: 9 page

Effect of angiotensin receptor neprilysin inhibitors on left atrial remodeling and prognosis in heart failure

Aims The angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, confers additional protective effects compared with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) in terms of reversed left ventricular (LV) remodelling and improves the prognosis of patients with heart failure (HF). However, few studies have examined the effects of ARNI on the left atrium. Accordingly, this study compared the effects of ARNI and ACEI/ARB on left atrial (LA) remodelling in heart failure with reduced ejection fraction (HFrEF). Methods and results This was a single-centre retrospective study of patients with HFrEF hospitalized at the First Affiliated Hospital of Dalian Medical University between 26 February 2016 and 8 July 2020. Patients were classified into ARNI and ACEI/ARB groups and further subgroups based on the left atrial volume index (LAVI): mildly abnormal (29 mL/m2 ≤ LAVI < 34 mL/m2), moderately abnormal (34 mL/m2 ≤ LAVI < 40 mL/m2), and severely abnormal (LAVI ≥ 40 mL/m2). The primary endpoint was changes in LA parameters by echocardiography. The secondary endpoint was all-cause mortality. A total of 336 patients (mean age: 64.11 ± 12.86, 30.06% female) were included. Except those lost to follow-up, 274 HFrEF patients remained, with 144 cases in the ARNI group and 130 cases in the ACEI/ARB group. Greater reductions from baseline were seen with ARNI in LA diameter (LAD) (P = 0.013, t-test), superior and LA superior–inferior diameter (LASID) (P < 0.0001), LA transverse diameter (LATD) (P < 0.0001), LA volume (LAV) (P < 0.0001), LAVI (P < 0.0001), and LA sphericity index (LASI) (P < 0.0001). Over a mean follow-up of 19.40 months, 97 patients (67.3%) in the ARNI group and 29 patients (22.3%) in the ACEI/ARB group showed LA reverse remodelling (LARR). Kaplan–Meier analysis showed significantly lower overall mortality in the ARNI group compared with the ACEI/ARB group (P = 0.048, log-rank test). The mildly abnormal LAVI group of ARNI patients showed a reduction in mortality compared with ACEI/ARB patients (P = 0.044). However, no significant difference was observed for the moderately abnormal (P = 0.571) or severely abnormal LAVI groups (P = 0.609), suggesting that early initiation of ARNI was associated with a better prognosis. Conclusions In this proof-of-concept study, ARNI use showed greater effects on LARR and was associated with a better prognosis compared with ACEI/ARB use in HFrEF. Early initiation of ARNI in the HF disease process may produce greater benefit, but this needs to be confirmed in future studies

The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status.

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing

Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer

SummaryTumor cells commonly have increased glucose uptake and lactate accumulation. Lactate is produced from pyruvate by lactate dehydrogenase A (LDH-A), which is frequently overexpressed in tumor cells and is important for cell growth. Elevated transcription by c-Myc or HIF1α may contribute to increased LDH-A in some cancer types. Here, we show that LDH-A is acetylated at lysine 5 (K5) and that this acetylation inhibits LDH-A activity. Furthermore, the K5-acetylated LDH-A is recognized by the HSC70 chaperone and delivered to lysosomes for degradation. Replacement of endogenous LDH-A with an acetylation mimetic mutant decreases cell proliferation and migration. Importantly, K5 acetylation of LDH-A is reduced in human pancreatic cancers. Our study reveals a mechanism of LDH-A upregulation in pancreatic cancers

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes.

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (&gt;95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types

Effects of the probiotic Bacillus amyloliquefaciens on the growth, immunity, and disease resistance of Haliotis discus hannai

Abstract(#br)The effects of a diet containing the probiotic Bacillus amyloliquefaciens on the survival and growth of Haliotis discus hannai were evaluated by measuring growth and hematological parameters and the expression levels of nonspecific immune genes. In addition, the abalone’s response to Vibrio parahaemolyticus infection was assessed. H. discus hannai (shell length: 29.35 ± 1.81 mm, body weight: 4.28 ± 0.23 g) were exposed to an 8-week culture experiment in indoor aquariums and a 2-week V. parahaemolyticus artificial infection experiment. In each experiment, the control group (C) was fed daily with the basal feed; the experimental groups were fed daily with the experimental feed, prepared by spraying B. amyloliquefaciens onto the basal feed at final concentrations of 10 3 (group A1), 10 5 (A2), and 10 7 (A3) cfu/g. The survival rate, body weight specific growth rate, and food conversion efficiency in A2 and A3 were significantly higher than those in A1 and C ( P < 0.05). The total number of blood lymphocytes, the O 2 − and NO levels produced from respiratory burst, the activities of acid phosphatase, superoxide dismutase, and catalase, and the expression levels of catalase and thiol peroxidase in A2 were not significantly different from those in A3, but these factors were significantly higher in A2 compared to A1 and C ( P < 0.05). The total antioxidant capacity and expression levels of glutathione S-transferase in A1, A2 and A3 were significantly higher than those in C ( P < 0.05). At day 9 after infection with V. parahaemolyticus , all abalone in C were dead; at the end of the experiment, the cumulative mortality of abalone in A2 was significantly lower than that in any other group ( P < 0.05). Thus, the experimental feed containing 10 5 cfu/g B. amyloliquefaciens not only facilitated the food intake and growth of abalone, but also effectively enhanced their non-specific immunity and resistance to V. parahaemolyticus infection. In this regard, B. amyloliquefaciens may be a useful probiotic strain for abalone aquaculture

Sulfur Fixation by Chemically Modified Red Mud Samples Containing Inorganic Additives: A Parametric Study

Sulfur retention ability of Bayer red mud from alumina plant was investigated. Bayer red mud modified by fusel salt and waste mother liquor of sodium ferrocyanide as the main sulfur fixation agent and the calcium based natural mineral materials as servicing additives; the experimental results showed the following: (1) Through 10 wt% waste mother liquor of sodium ferrocyanide modifying Bayer red mud, sulfur fixation rate can increase by 13 wt%. (2) Magnesium oxide can obviously improve the sulfur fixation performance of Bayer red mud and up to a maximum sulfur fixation rate of 47 wt% at adding 1 wt% magnesium oxide. (3) Dolomite enhanced the sulfur fixation performances with the sulfur fixation rate of 68 wt% in optimized condition. (4) Vermiculite dust reduced sulfur dioxide during the fixed-sulfur process of modified Bayer red mud, and the desulphurization ration could reach up to a maximum 76 wt% at 950°C. (5) An advanced three-component sulfur fixation agent was investigated, in which the optimized mass ratio of modified Bayer red mud, dolomite, and vermiculite dust was 70 : 28 : 2 in order, and its sulfur fixation efficiency has reached to a maximum 87 wt% under its 20 wt% dosage in the coal

Model of a multiverse providing the dark energy of our universe

It is shown that the dark energy presently observed in our universe can be regarded as the energy of a scalar field driving an inflation-like expansion of a multiverse with ours being a subuniverse among other parallel universes. A simple model of this multiverse is elaborated: Assuming closed space geometry, the origin of the multiverse can be explained by quantum tunneling from nothing; subuniverses are supposed to emerge from local fluctuations of separate inflation fields. The standard concept of tunneling from nothing is extended to the effect that in addition to an inflationary scalar field, matter is also generated, and that the tunneling leads to an (unstable) equilibrium state. The cosmological principle is assumed to pertain from the origin of the multiverse until the first subuniverses emerge. With increasing age of the multiverse, its spatial curvature decays exponentially so fast that, due to sharing the same space, the flatness problem of our universe resolves by itself. The dark energy density imprinted by the multiverse on our universe is time-dependent, but such that the ratio $w{=}\varrho/(c^2p)$ of its mass density and pressure (times $c^2$) is time-independent and assumes a value $-1{+}\epsilon$ with arbitrary $\epsilon{>}0$. $\epsilon$ can be chosen so small, that the dark energy model of this paper can be fitted to the current observational data as well as the cosmological constant model.Comment: 32 pages, 4 figure