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Aims MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. Methods and results Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading, and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the phosphoinositide 3-kinase/protein kinase B pathway, enhancing platelet activation through activating the integrin αIIbβ3-mediated outside-in signalling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease in platelet activity. Conclusion Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Late spring coldness (LSC) is the main limiting factor threatening wheat yield and quality stability. Optimal nutrient management is beneficial in mitigating the harms of LSC by improving wheat root physiology. This study proposed a nutrient management strategy that postponed the application of phosphorus (P) and potassium (K), effectively strengthening wheat's defense against LSC. This experiment used the winter cultivar "Yannong19" (YN 19) as plant material for two consecutive years (2021–2022 and 2022–2023). Two fertilizer treatments were used: traditional P and K fertilizers application (R1: base fertilizer: jointing fertilizer = 10:0) and postponed P and K fertilizers application (R2: base fertilizer: jointing fertilizer = 5:5); wheat plants at the anther connective formation stage shifted to temperature-controlled phytotrons for normal (T0, 11 °C/4 h) and low temperatures (T1, 4 °C/4 h; T2, −4 °C/4 h) as treatments of LSC. The results showed that under low temperature (LT) treatment, compared with R1, the R2 treatment increased the concentrations of osmotic adjustment substances (soluble sugars and soluble protein contents by 6.2–8.7% and 3.0–8.9%), enhanced activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase activities by 2.2–9.1%, 6.2–9.7% and 4.2–8.4%), balanced the hormone concentrations (increased IAA and GA3 contents by 2.8–17.5% and 10.4–14.1% and decreased ABA contents by 7.2–14.3%), and reduced the toxicity (malondialdehyde, hydrogen peroxide content and O2·− production rate by 5.7–12.4%, 17.7–22.8% and 19.1–19.1%) of the cellular membranes. Furthermore, the wheat root physiology in R2 significantly improved as the root surface area and dry weight increased by 5.0–6.6% and 4.7–6.6%, and P and K accumulation increased by 7.4–11.3% and 12.2–15.4% compared to R1, respectively. Overall, the postponed application of P and K fertilizers enhanced the physiological function of the root system, maintained root morphology, and promoted the accumulation of wheat nutrients under the stress of LSC. [ABSTRACT FROM AUTHOR]

Anaerobic digestion (AD) has the great potential to treat organic waste and achieve remarkable results effectively. However, it is very tough to establish an accurate mechanistic model for this process. Data-driven modeling technology has opened a new door to solving this problem. While when the sample set is small, traditional data-driven modeling methods are often powerless. In this paper, an effective method is proposed for data-driven high-precision modeling in small sample scenarios. A time series generative adversarial network (TimeGAN) is first utilized to augment the original high-quality small-sample data collected during the AD methane production. A novel hybrid kernel extreme learning machine (HKELM) is then designed to form a better structure of the data-driven model, whose regularization coefficient C0 is optimized by the sparrow search algorithm (SSA). Finally, this semi-finished model (SSA-HKELM) is trained by the augmented data to form the final mathematical model (TimeGAN-SSA-HKELM) for the AD methane generation process. Comparative experiments of the methane daily production prediction error have verified the effectiveness of the method, which can be extended to other similar small sample data-driven modeling scenarios. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

As the stress-inducible isoform of the heat-shock protein 90 (HSP90), the HSP90AA1 gene encodes HSP90α and plays an important role in heat stress (HS) response. Therefore, this study aimed to investigate the role of the HSP90AA1 gene in cellular responses during HS and to identify functional SNPs associated with thermotolerance in Holstein cattle. For the in vitro validation experiment of acute HS, cells from the Madin-Darby bovine kidney cell line were exposed to 42°C for 1 h, and various parameters were assessed, including cell apoptosis, cell autophagy, and the cellular functions of HSP90α by using its inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). Furthermore, the polymorphisms identified in the HSP90AA1 gene and their functions related to HS were validated in vitro. Acute HS exposure induced cell apoptosis, cell autophagy, and upregulated expression of the HSP90AA1 gene. Inhibition of HSP90α by 17-AAG treatment had a significant effect on the expression of the HSP90α protein and increased cell apoptosis. However, autophagy decreased in comparison to the control treatment when cells were exposed to 42°C for 1 h. Five SNPs identified in the HSP90AA1 gene were significantly associated with rectal temperature and respiration score in Holstein cows, in which the rs109256957 SNP is located in the 3′ untranslated region (3′ UTR). Furthermore, we demonstrated that the 3′ UTR of HSP90AA1 is a direct target of bta-miR-1224 by cell transfection with exogenous microRNA (miRNA) mimic and inhibitor. The luciferase assays revealed that the SNP rs109256957 affects the regulation of bta-miR-1224 binding activity and alters the expression of the HSP90AA1 gene. Heat stress–induced HSP90AA1 expression maintains cell survival by inhibiting cell apoptosis and increasing cell autophagy. The rs109256957 located in the 3′ UTR region is a functional variation and it affects the HSP90AA1 expression by altering its binding activity with bta-miR-1224, thereby associating with the physiological parameters of Holstein cows. [ABSTRACT FROM AUTHOR]

Organic matter and metal elements are commonly co-enriched in marine black shales. However, the element types vary among different shales and the relevant mechanisms of organo-metal co-enrichment are still unclear. The super-enrichment of organic matter and nickel in the ore bed of Early Cambrian marine black shale of southern China provides an ideal opportunity to investigate this mechanism. Herein, to clarify the coenrichment mechanism of organic matter and, the laminated structure of this ore bed was characterized and the geochemical and mineralogical proxies of different laminae were analyzed. The results indicated that there are four types of laminae in this ore bed, namely, siliceous laminae, calcareous laminae, clay minerals laminae, and organic-rich laminae. Clay minerals laminae and organic-rich laminae were deposited under anoxic environments, while siliceous laminae were deposited under strong oxidizing to anoxic environments. Neither organic matter nor are distributed homogeneously in the ore bed; organic matter is mainly concentrated in organic-rich laminae, while is largely enriched in clay minerals laminae. Clay minerals and organic matter have strong adsorption capacity for, and the adsorption capacity of clay minerals (such as illite) for is stronger than that of organic matter. Hydrothermal events and terrestrial input are key factors affecting the paleoenvironment and laminated structure during the deposition of the ore bed. Although organic matter and are co-enriched in the ore bed, their enrichment stages and conditions vary according to the geochemical differences among laminae. [ABSTRACT FROM AUTHOR]

Purpose: The authors construct two time-varying political connection (PC) indexes to measure a firm's political tendencies toward ruling and opposing parties and analyze whether a firm with ruling party tendencies obtains better bank loan contracts compared to the contracts obtained by a firm with opposing party tendencies and a firm with fixed PC tendencies. Design/methodology/approach: Linguistic text mining is used to construct the two time-varying PC indexes from news sources that reflect the tone and frequencies of characteristic texts to determine a firm's tendencies to favor the ruling or opposing parties. Findings: The results show that varying PC firms connected to the ruling party receive preferential loan contracts when their political tendencies increase but varying PC firms connected to the opposition party do not. In contrast, fixed PC firms gain similar benefits only when the connection is determined in the presidential election year but not in other years. Firms supporting two parties receive minimal financial rewards in terms of loan terms. Originality/value: In past studies, once a firm is identified as having a connection with a political party, it is assumed to have PC throughout the sample period (i.e. fixed PC firms). The authors lift this assumption and examine how varying PC affect bank loan contracts. The two time-varying PC indexes can identify a firm's more immediate party tendencies and more precise effects of a firm's party tendencies on bank loan contracts. [ABSTRACT FROM AUTHOR]