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1.
Breath metabolomics for diagnosis of acute respiratory distress syndrome.
Zhang, S, Hagens, LA, Heijnen, NFL, Smit, MR, Brinkman, P, Fenn, D, van der Poll, T, Schultz, MJ, Bergmans, DCJJ, Schnabel, RM, et al
Critical care (London, England). 2024;(1):96
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.
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2.
Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.
Bergmark, BA, Marston, NA, Prohaska, TA, Alexander, VJ, Zimerman, A, Moura, FA, Murphy, SA, Goodrich, EL, Zhang, S, Gaudet, D, et al
The New England journal of medicine. 2024
Abstract
BACKGROUND Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. METHODS In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. RESULTS A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups. CONCLUSIONS In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).
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3.
RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy.
Liu, WW, Zheng, SQ, Li, T, Fei, YF, Wang, C, Zhang, S, Wang, F, Jiang, GM, Wang, H
Signal transduction and targeted therapy. 2024;(1):70
Abstract
Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.
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4.
Characteristic analysis and fermentation optimization of a novel Aureobasidium pullulans RM1603 with high pullulan yield.
Chen, J, Lu, Y, Liu, L, Bai, R, Zhang, S, Hao, Y, Xu, F, Wei, B, Zhao, H
Journal of bioscience and bioengineering. 2024;(5):335-343
Abstract
A high-yielding microbial polysaccharide-producing strain, named RM1603, was isolated from rhizosphere soil and identified by morphological and phylogenetic analysis. The extracellular polysaccharides (EPS) were identified by thin-layer chromatography and infrared spectroscopy. The fermentation conditions were optimized by single factor experiments in shake flasks and a 5-L fermentor. The results of morphological and phylogenetic tree analysis showed that RM1603 was a strain of Aureobasidium pullulans. Its microbial polysaccharide was identified as pullulan, and the EPS production capacity reached 33.07 ± 1.03 g L-1 in shake flasks. The fermentation conditions were optimized in a 5-L fermentor, and were found to encompass an initial pH of 6.5, aeration rate of 2 vvm, rotor speed of 600 rpm, and inoculum size of 2 %. Under these conditions, the pullulan yield of RM1603 reached 62.52 ± 0.24 g L-1. Thus, this study contributes RM1603 as a new isolation with high-yielding pullulan and potential application value in biotechnology.
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5.
Performance of Artificial Intelligence in Detecting Diabetic Macular Edema From Fundus Photography and Optical Coherence Tomography Images: A Systematic Review and Meta-analysis.
Lam, C, Wong, YL, Tang, Z, Hu, X, Nguyen, TX, Yang, D, Zhang, S, Ding, J, Szeto, SKH, Ran, AR, et al
Diabetes care. 2024;(2):304-319
Abstract
BACKGROUND Diabetic macular edema (DME) is the leading cause of vision loss in people with diabetes. Application of artificial intelligence (AI) in interpreting fundus photography (FP) and optical coherence tomography (OCT) images allows prompt detection and intervention. PURPOSE To evaluate the performance of AI in detecting DME from FP or OCT images and identify potential factors affecting model performances. DATA SOURCES We searched seven electronic libraries up to 12 February 2023. STUDY SELECTION We included studies using AI to detect DME from FP or OCT images. DATA EXTRACTION We extracted study characteristics and performance parameters. DATA SYNTHESIS Fifty-three studies were included in the meta-analysis. FP-based algorithms of 25 studies yielded pooled area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of 0.964, 92.6%, and 91.1%, respectively. OCT-based algorithms of 28 studies yielded pooled AUROC, sensitivity, and specificity of 0.985, 95.9%, and 97.9%, respectively. Potential factors improving model performance included deep learning techniques, larger size, and more diversity in training data sets. Models demonstrated better performance when validated internally than externally, and those trained with multiple data sets showed better results upon external validation. LIMITATIONS Analyses were limited by unstandardized algorithm outcomes and insufficient data in patient demographics, OCT volumetric scans, and external validation. CONCLUSIONS This meta-analysis demonstrates satisfactory performance of AI in detecting DME from FP or OCT images. External validation is warranted for future studies to evaluate model generalizability. Further investigations may estimate optimal sample size, effect of class balance, patient demographics, and additional benefits of OCT volumetric scans.
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6.
Extraction, purification, structural characteristics and biological properties of the polysaccharides from Armillaria mellea (Vahl) P. Kumm.: A review.
Chen, X, Liu, Y, Ren, L, Dai, X, Zhao, J, Gao, C, Zhang, S, Dong, J, Zhao, Z, Li, Y, et al
International journal of biological macromolecules. 2024;(Pt 1):129175
Abstract
Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.
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7.
PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.
Liu, P, Sun, D, Zhang, S, Chen, S, Wang, X, Li, H, Wei, F
Cell & bioscience. 2024;(1):21
Abstract
BACKGROUND Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. MAIN BODY In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. CONCLUSION Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.
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8.
Nanocellulose/carbon nanotube/manganese dioxide composite electrodes with high mass loadings for flexible supercapacitors.
Zhang, S, Li, L, Liu, Y, Li, Q
Carbohydrate polymers. 2024;:121661
Abstract
The increasing commercialization of flexible electronic products has sparked a rising interest in flexible wearable energy storage devices. Supercapacitors are positioned as one of the systems with the most potential due to their distinctive advantages: high power density, rapid charge and discharge rates, and long cycle life. However, electrode materials face challenges in providing excellent mechanical strength while ensuring sufficient energy density. This study presents a method for constructing a flexible composite electrode material with high capacitance and mechanical performance by electrochemically depositing high-quality manganese dioxide (MnO2) onto the surface of a nanocellulose (CNF) and carbon nanotube (CNT) conductive film. In this electrode material, the CNF/CNT composite film serves as a flexible conductive substrate, offering excellent mechanical properties (modulus of 3.3 GPa), conductivity (55 S/cm), and numerous active sites. Furthermore, at the interface between MnO2 and the CNF/CNT substrate, C-O-Mn bonds are formed, promoting a tight connection between the composite materials. The assembled symmetric flexible supercapacitor (FSC) demonstrates impressive performance, with an areal specific capacitance of 934 mF/cm2, an energy density of 43.10 Wh/kg, a power density of 166.67 W/kg and a long cycle life (85 % Capacitance retention after 10,000 cycles), suggesting that they hold promise for FSC applications.
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9.
Exploring the relationship between hyperlactatemia and anemia.
Zhang, S, Liu, W, Ganz, T, Liu, S
Trends in endocrinology and metabolism: TEM. 2024;(4):300-307
Abstract
Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers, and genetic disorders. For instance, hyperlactatemia leads to iron restriction by upregulating hepatic hepcidin expression. Increasing evidence also points to lactate as a crucial signaling molecule rather than merely a metabolic byproduct. Here, we discuss the mutual influence between anemia and hyperlactatemia. This opinion calls for a reconsideration of the multifaceted roles of lactate and lactylation in anemia and emphasizes the need to fill knowledge gaps, including the dose dependence of lactate's effects, its sources, and its subcellular localization.
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10.
iACVP-MR: Accurate Identification of Anti-coronavirus Peptide based on Multiple Features Information and Recurrent Neural Network.
Liang, Y, Ma, X, Zhang, S, Li, J
Current medicinal chemistry. 2024
Abstract
BACKGROUND Over the years, viruses have caused human illness and threatened human health. Therefore, it is pressing to develop anti-coronavirus infection drugs with clear function, low cost, and high safety. Anti-coronavirus peptide (ACVP) is a key therapeutic agent against coronavirus. Traditional methods for finding ACVP need a great deal of money and man power. Hence, it is a significant task to establish intelligent computational tools to able rapid, efficient and accurate identification of ACVP. METHODS In this paper, we construct an excellent model named iACVP-MR to identify ACVP based on multiple features and recurrent neural networks. Multiple features are extracted by using reduced amino acid component and dipeptide component, compositions of k-spaced amino acid pairs, BLOSUM62 encoder according to the N5C5 sequence, as well as second-order moving average approach based on 16 physicochemical properties. Then, two recurrent neural networks named long-short term memory (LSTM) and bidirectional gated recurrent unit (BiGRU) combined attention mechanism are used for feature fusion and classification, respectively. RESULTS The accuracies of ENNAVIA-C and ENNAVIA-D datasets under the 10-fold cross-validation are 99.15% and 98.92%, respectively, and other evaluation indexes have also obtained satisfactory results. The experimental results show that our model is superior to other existing models. CONCLUSION The iACVP-MR model can be viewed as a powerful and intelligent tool for the accurate identification of ACVP. The datasets and source codes for iACVP-MR are freely downloaded at https://github.com/yunyunliang88/iACVP-MR.