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Chromatin accessibility dynamics insight into crosstalk between regulatory landscapes in poplar responses to multiple treatments.
Wang, W, Chen, K, Chen, N, Gao, J, Zhang, W, Gong, J, Tong, S, Chen, Y, Li, Y, Feng, Y, et al
Tree physiology. 2023;(6):1023-1041
Abstract
Perennial trees develop and coordinate endogenous response signaling pathways, including their crosstalk and convergence, to cope with various environmental stresses which occur simultaneously in most cases. These processes are involved in gene transcriptional regulations that depend on dynamic interactions between regulatory proteins and corresponding chromatin regions, but the mechanisms remain poorly understood in trees. In this study, we detected chromatin regulatory landscapes of poplar under abscisic acid, methyl jasmonate, salicylic acid and sodium chloride (NaCl) treatment, through integrating ATAC-seq and RNA-seq data. Our results showed that the degree of chromatin accessibility for a given gene is closely related to its expression level. However, unlike the gene expression that shows treatment-specific response patterns, changes in chromatin accessibility exhibit high similarities under these treatments. We further proposed and experimentally validated that a homologous gene copy of RESPONSIVE TO DESICCATION 26 mediates the crosstalk between jasmonic acid and NaCl signaling pathways by directly regulating the stress-responsive genes and that circadian clock-related transcription factors like REVEILLE8 play a central role in response of poplar to these treatments. Overall, our study provides a chromatin insight into the molecular mechanism of transcription regulatory networks in response to different environmental stresses and raises the key roles of the circadian clock of poplar to adapt to adverse environments.
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The regulation of circRNA and lncRNAprotein binding in cardiovascular diseases: Emerging therapeutic targets.
Zhao, H, Tan, Z, Zhou, J, Wu, Y, Hu, Q, Ling, Q, Ling, J, Liu, M, Ma, J, Zhang, D, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;:115067
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Abstract
Noncoding ribonucleic acids (ncRNAs) are a class of ribonucleic acids (RNAs) that carry cellular information and perform essential functions. This class encompasses various RNAs, such as small nuclear ribonucleic acids (snRNA), small interfering ribonucleic acids (siRNA) and many other kinds of RNA. Of these, circular ribonucleic acids (circRNAs) and long noncoding ribonucleic acids (lncRNAs) are two types of ncRNAs that regulate crucial physiological and pathological processes, including binding, in several organs through interactions with other RNAs or proteins. Recent studies indicate that these RNAs interact with various proteins, including protein 53, nuclear factor-kappa B, vascular endothelial growth factor, and fused in sarcoma/translocated in liposarcoma, to regulate both the histological and electrophysiological aspects of cardiac development as well as cardiovascular pathogenesis, ultimately leading to a variety of genetic heart diseases, coronary heart disease, myocardial infarction, rheumatic heart disease and cardiomyopathies. This paper presents a thorough review of recent studies on circRNA and lncRNAprotein binding within cardiac and vascular cells. It offers insight into the molecular mechanisms involved and emphasizes potential implications for treating cardiovascular diseases.
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Insight into the Mechanisms of Nitride Films with Excellent Hardness and Lubricating Performance: A Review.
Wu, X, Jiang, Y, Wu, T, Zuo, B, Bian, S, Lu, K, Zhao, L, Yu, L, Xu, J
Nanomaterials (Basel, Switzerland). 2023;(15)
Abstract
Transition metal nitride (TMN) films with excellent hardness and lubricating performance are versatile low dimension materials, which are widely used in various fields including industries, transportation, aerospace, and so on. This paper introduces one film design strategy and provides a review of the mechanisms for strengthening and lubricating nitride films. The design strategy refers to two aspects which determine the structures, the performance, the components, and the chemical constitutions of nitride films The strengthening mechanisms of nitride films are then illuminated in detail, including the solid solution effect, the grain size effect, the secondary phase effect, the stress or stress field effect, the template effect, and the valence electron concentration effect. Five lubricating mechanisms are next summarized, including the easy-shear nature, the tribo-chemical reactions, the lubricious fluorides, the textured contact surface, and the synergistic effect. This paper aims to give a comprehensive introduction for understanding the mechanisms of strengthening and lubrication of nitride films for students and researchers, as well as to understand the current research progress in nitride films for exploring research gaps.
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Evaluation of Safety, Biodistribution, and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analog 177 Lu-DOTA-EB-TATE With and Without Amino Acid Infusion.
Jiang, Y, Liu, Q, Wang, G, Zhang, J, Zhu, Z, Chen, X
Clinical nuclear medicine. 2023;(6):e289-e293
Abstract
PURPOSE Kidney is considered to be one of the dose-limiting organs in peptide receptor radionuclide therapy (PRRT). Amino acid cocktail infusion has been applied to reduce renal absorbed dose by inhibiting the proximal tubular reabsorption of the radiopeptide. An Evans blue-modified 177 Lu-labeled octreotate ( 177 Lu-DOTA-EB-TATE) has an extended circulation in the blood, which may make the amino acid infusion unnecessary. The aim of this study was to evaluate the safety, biodistribution, and dosimetry of 177 Lu-DOTA-EB-TATE with and without amino acid infusion. PATIENTS AND METHODS Ten patients with metastatic neuroendocrine tumors were randomly divided into 2 groups. The effect of amino acid infusion on renal uptake was assessed in a crossover randomized setting. Group A received 177 Lu-DOTA-EB-TATE at a dose of 3.7 GBq without amino acid infusion for the first cycle and with amino acid infusion for the second cycle; group B received 177 Lu-DOTA-EB-TATE at a dose of 3.7 GBq with amino acid infusion for the first cycle and without amino acid infusion for the second cycle. All patients underwent serial whole-body planar imaging at 1, 24, 96, and 168 hours and SPECT scan at 24 hours after radioligand administration. Abdominal CT was performed 2 days before PRRT for SPECT/CT fusion. The dosimetry was calculated using the HERMES software. Dosimetry evaluation was compared on a between-group and intrapatient basis. RESULTS Administrations of 177 Lu-DOTA-EB-TATE with or without amino acids were well tolerated. No grade 4 hematotoxicity was observed in any of the patients. Grade 3 thrombocytopenia was reported in 1 patient. No nephrotoxicity of any grade was recorded. No significant difference was observed in creatinine (75.1 ± 21.7 vs 67.5 ± 18.1 μmol/L, P = 0.128), blood urea nitrogen (4.5 ± 0.8 vs 5.1 ± 1.4 mmol/L, P = 0.612), or GFR (109.3 ± 25.2 vs 100.9 ± 24.9 mL/min, P = 0.398) before and after PRRT. For each cycle, there was no significant difference in whole-body effective dose, kidney effective dose, as well as residence time of the kidneys between group A and B ( P > 0.05). By intrapatient comparison, without and with amino acid infusion also did not show significant difference in whole-body effective dose (0.14 ± 0.05 vs 0.12 ± 0.04 mSv/MBq, P = 0.612), kidney effective dose (1.09 ± 0.42 vs 0.73 ± 0.31 mSv/MBq, P = 0.093), and residence time of the kidneys (2.95 ± 1.58 vs 3.13 ± 1.11 hours, P = 0.674). CONCLUSIONS 177 Lu-DOTA-EB-TATE PRRT with and without amino acid infusion demonstrated a favorable safety profile in neuroendocrine tumor patients. Administration of 177 Lu-DOTA-EB-TATE without amino acid infusion has acceptable slightly increased kidney absorbed dose and residence time of the kidneys, and does not affect kidney function. Further investigation in a larger cohort and long-term follow-up are warranted.
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Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.
Wang, H, Zhang, J, Liu, J, Jiang, Y, Fu, L, Peng, S
Frontiers in molecular biosciences. 2023;:1124956
Abstract
Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor-DEG-microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson's correlation analysis. Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC. Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.
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Ligustri Lucidi Fructus, a traditional Chinese Medicine: Comprehensive review of botany, traditional uses, chemical composition, pharmacology, and toxicity.
Cao, M, Wu, J, Peng, Y, Dong, B, Jiang, Y, Hu, C, Yu, L, Chen, Z
Journal of ethnopharmacology. 2023;:115789
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ligustri Lucidi Fructus (LLF) is one of the usual Chinese herbs that has long been used with high therapeutic and condition value. LLF is used for the treatment of dizziness and tinnitus, soreness and weakness of the waist and knees, premature greying of the hair, the darkness of the eyes, internal heat and thirst, bone steam and hot flashes and other symptoms. AIM OF THE STUDY This review reviews botany, traditional uses, processing, phytochemistry, quality control, pharmacology, toxicity and pharmacokinetics to better understand its therapeutic potential. MATERIALS AND METHODS The literature on LLF was obtained from Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WAN FANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS So far, Multiple chemical components were isolated and identified from LLF, mainly including terpenoids and flavonoids. Modern studies have shown that LLF extracts and compounds have a wide range of pharmacological effects, including antitumor, liver protection, blood glucose, lipid-lowering, immune regulation, and other aspects. CONCLUSIONS LLF occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant and its chemical composition, pharmacological activity, quality control, toxicity and pharmacokinetics.
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Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.
Zhang, Y, Yan, B, Shen, S, Song, X, Jiang, Y, Shi, L, Zhao, C, Yang, Y, Jiang, L, Li, J, et al
EClinicalMedicine. 2023;:102076
Abstract
BACKGROUND Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. METHODS A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. FINDINGS Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. INTERPRETATION These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. FUNDING KeyMed Biosciences (Chengdu) Limited.
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The Value of Visfatin in the Prediction of Metabolic Syndrome: A Systematic Review and Meta-Analysis.
Jiang, Y, Zhou, L
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2023;(9):610-616
Abstract
Various studies have shown that visfatin may be connected to metabolic syndrome (MS). However, epidemiological studies yielded conflicting outcomes. The purpose of this article was to highlight the relationship between the plasma visfatin level and MS risk by conducting a meta-analysis of available literature. A comprehensive literature search of eligible studies was done up to January 2023. Data were presented as standard mean difference (SMD). Observational methodological meta-analysis was conducted to assess the relationships between visfatin levels and MS. The visfatin levels between patients with MS or not were calculated by SMD and 95% confidence interval (CI) using the random-effects model. Funnel plot (visually inspect publication bias), Egger's linear regression test and Begger's linear regression test were applied to describe the risk of publication bias. A sensitivity analysis was performed via sequentially omitting each of the study one by one. In total, 16 eligible studies comprising 1016 cases and 1414 healthy controls finally enrolled in the current meta-analysis for pooling meta-analysis. Overall, the meta-analysis results revealed that visfatin levels in MS patients were significantly greater than that of controls group (SMD: 0.60, 95% CI=0.18-1.03, I2=95%, p<0.001). The results of the subgroup analysis showed that gender did not affect the results of meta-analysis. This meta-analysis shed light on the fact that circulating visfatin levels were significantly higher in patients with MS than in the controls group. Visfatin may a chance to predict the occurrence of MS.
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Synergistic effects of aerobic exercise and transcranial direct current stimulation on executive function and biomarkers in healthy young adults.
Ji, Y, Ni, X, Zheng, K, Jiang, Y, Ren, C, Zhu, H, Xiao, M, Wang, T
Brain research bulletin. 2023;:110747
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Abstract
OBJECTIVE This research explored the combined effects of transcranial direct current stimulation (tDCS) and aerobic exercise (AE) on executive function and specific serum biomarkers in healthy adults. METHODS Sixty healthy young adults were randomly assigned into tDCS+AE, tDCS only, or AE only groups. Interventions were carried out for 20 days. Executive functions were evaluated using tasks such as the 2,3-back task, the spatial working memory task, the Stroop test, T test, and hexagonal obstacle jump task. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), superoxide dismutase (SOD), glutamate, glutathione peroxidase 4 (GPX4) and iron ion, were analyzed pre- and post-intervention. RESULTS The tDCS+AE group showed superior enhancements in executive function, evidenced by improved accuracy rates in 2,3-back tasks, better performance in the staircase task, and reduced reaction times in the incongruent reaction time of the Stroop task compared to other groups. Importantly, we found substantial changes in serum biomarkers: increased levels of BDNF and SOD, and decreased levels of MDA and glutamate in the tDCS+AE group. These changes were significantly different when compared with the tDCS and AE only groups. Notably, these alterations in serum biomarkers were correlated with improvements in executive function tasks, thus offering a potential physiological basis for the cognitive improvements witnessed. CONCLUSION The combined tDCS and AE intervention effectively improved executive function in healthy young adults, with the improvements linked to changes in key serum biomarkers. The results emphasize the potential of combined tDCS and AE interventions in engaging multiple physiological pathways to enhance executive function.
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Tumor microenvironmental nutrients, cellular responses, and cancer.
Lobel, GP, Jiang, Y, Simon, MC
Cell chemical biology. 2023;(9):1015-1032
Abstract
Over the last two decades, the rapidly expanding field of tumor metabolism has enhanced our knowledge of the impact of nutrient availability on metabolic reprogramming in cancer. Apart from established roles in cancer cells themselves, various nutrients, metabolic enzymes, and stress responses are key to the activities of tumor microenvironmental immune, fibroblastic, endothelial, and other cell types that support malignant transformation. In this article, we review our current understanding of how nutrient availability affects metabolic pathways and responses in both cancer and "stromal" cells, by dissecting major examples and their regulation of cellular activity. Understanding the relationship of nutrient availability to cellular behaviors in the tumor ecosystem will broaden the horizon of exploiting novel therapeutic vulnerabilities in cancer.
