ABSTRACT
Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org, form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development.
Subject(s)
Neoplasms , Proteogenomics , Humans , Proteogenomics/methods , Neoplasms/genetics , Neoplasms/drug therapy , Neoplasms/therapy , Neoplasms/metabolism , Molecular Targeted Therapy , Immunotherapy/methods , Antigens, Neoplasm/metabolism , Antigens, Neoplasm/genetics , Cell Line, Tumor , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Peptides/metabolism , Proteomics , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolismABSTRACT
Achieving timely, reversible, and long-range remote tunability over surface wettability is highly demanded across diverse fields, including nanofluidic systems, drug delivery, and heterogeneous catalysis. Herein, using molecular dynamic simulations, we show, for the first time, a theoretical design of electrowetting to achieve remotely controllable surface wettability via using a terahertz wave. The key idea driving the design is the unique terahertz collective vibration identified in the vicinal subnanoscale water layer, which is absent in bulk water, enabling efficient energy transfer from the terahertz wave to the rotational motion of the vicinal subnanoscale water layer. Consequently, a frequency-specific alternating terahertz electric field near the critical strength can significantly affect the local hydrogen-bonding network of the contact water layer on the solid surface, thereby achieving tunable surface wettability.
ABSTRACT
Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti-inflammatory, anti-obesity and anti-tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF-α-stimulated HaCaT cells and DNCB-induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL-4, IL-13, TNF-α, IL-5, IL-31, IL-33, IgE, TSLP, IL-17, IL-23, IL-1ß, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF-α-induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi-1 (a mitochondrial fission inhibitor) and Ezrin-specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co-immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin-mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.
Subject(s)
Cytokines , Cytoskeletal Proteins , Dermatitis, Atopic , Mice, Inbred BALB C , Mitochondrial Dynamics , Pentacyclic Triterpenes , Triterpenes , Animals , Mitochondrial Dynamics/drug effects , Pentacyclic Triterpenes/pharmacology , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Dermatitis, Atopic/metabolism , Humans , Triterpenes/pharmacology , Mice , Cytokines/metabolism , Cytoskeletal Proteins/metabolism , Cytoskeletal Proteins/genetics , Thymic Stromal Lymphopoietin , Disease Models, Animal , Mitochondria/metabolism , Mitochondria/drug effects , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism , HaCaT Cells , Phosphorylation/drug effectsABSTRACT
The multi-level structure is a strategy to enhance the mechanical properties of dung beetle leg joints. Under external loads, the microstructure facilitates energy dissipation and prevents crack extension. The macrostructure aids in transferring the load to more reliable parts. The connection established by the two hemispheres is present in the dung beetle leg joint. The micron-layered and nanoscale crystal structures further constitute the leg joint with excellent mechanical properties. The maximum compression fracture force is ≈101000 times the weight of the leg. Here, the structural design within the dung beetle leg joints and reveal the resulting mechanical response and enhancement mechanisms is determined. A series of beetle leg joints where the macrostructure and microstructure of the dung beetle leg provide mechanical strength at critical strains while avoiding catastrophic failure by transferring the load from the joint to the exoskeleton of the femur is highlighted. Nanocrystalline structures and fiber layers contribute to crack propagation of the exoskeleton. Based on this, the bionic joint with multi-level structures using resin and conducted a series of tests to verify their effectiveness is prepared. This study provides a new idea for designing and optimizing high-load joints in engineering.
ABSTRACT
Fringe projection profilometry plays an important role for quality control in production line. However, it is facing challenges in the measurement of objects with intricate structures and high dynamic range that involved in precision manufacturing and semiconductor packaging. In this paper, a multi-view fringe projection profilometry system, which deploys a vertical telecentric projector and four oblique tilt-shift cameras, is presented to address the "blind spots" caused by shadowing, occlusion and local specular reflection. A flexible and accurate system calibration method is proposed, in which the corrected pinhole imaging model is used to calibrate the telecentric projection, and the unified calibration is performed by bundle adjustment. Experimental results show that the 3D repeated measurement error and standard deviation are no more than 10â µm within a measurable volume of 70 × 40 × 20 mm3. Furthermore, a group of experiments prove that the developed system can achieve complete and accurate 3D measurement for high dynamic range surfaces with complex structures.
ABSTRACT
This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of methionine (Met)-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into three groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into four groups. The second experiment included a control group and three MetRS inhibitor (REP8839) groups. The third experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1·0 mg/kg body weight REP8839, which was the selected dose for the third experiment. Experiment 3 showed that Met supplementation increased crop development, crop milk protein synthesis and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the co-immunoprecipitation results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.
ABSTRACT
L-Glutamic acid (L-Glu) is a basic unit of proteins and also serves as an important neurotransmitter in the central nervous system. Its structural properties are critical for biological functions and selective receptor recognition. Although this molecule has been extensively studied, the low frequency vibrational behavior that is closely related to conformational changes and the intermolecular interactions between L-Glu and its receptors are still unclear. In this study, we acquired the fingerprint spectrum of L-Glu by using air plasma terahertz (THz) time-domain spectroscopy in the 0.5-18 THz range. The low frequency vibrational characteristics of L-Glu were investigated through density functional theory (DFT) calculations. The THz responses of the ligand binding domain of the NMDAR-L-Glu complex were studied by the ONIOM method, with a focus on discussing the normal modes and interactions of ligand L-Glu and water molecules. The results illustrate that THz spectroscopy exhibits a sensitive response to the influence of L-Glu on the structure of the NMDAR. The water molecules in proteins have various strong vibration modes in the THz band, showing specificity, diversity and complexity of vibrational behavior. There is potential for influencing and regulating the structural stability of the NMDAR-L-Glu complex through water molecules.
ABSTRACT
Antifungal peptides (AFPs) are emerging as promising candidates for advanced antifungal therapies because of their broad-spectrum efficacy and reduced resistance development. In silico design of AFPs, however, remains challenging, due to the lack of an efficient and well-validated quantitative assessment of antifungal activity. This study introduced an AFP design approach that leverages an innovative quantitative metric, named the antifungal index (AFI), through a three-step process, i.e., segmentation, single-point mutation, and global multipoint optimization. An exhaustive search of 100 putative AFP sequences indicated that random modifications without guidance only have a 5.97-20.24% chance of enhancing antifungal activity. Analysis of the search results revealed that (1) N-terminus truncation is more effective in enhancing antifungal activity than the modifications at the C-terminus or both ends, (2) introducing the amino acids within the 10-60% sequence region that enhance aromaticity and hydrophobicity are more effective in increasing antifungal efficacy, and (3) incorporating alanine, cysteine, and phenylalanine during multiple point mutations has a synergistic effect on enhancing antifungal activity. Subsequently, 28 designed peptides were synthesized and tested against four typical fungal strains. The success rate for developing promising AFPs, with a minimal inhibitory concentration of ≤5.00 µM, was an impressive 82.14%. The predictive and design tool is accessible at https://antifungipept.chemoinfolab.com.
Subject(s)
Antifungal Agents , Computer Simulation , Drug Design , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Amino Acid Sequence , Peptides/pharmacology , Peptides/chemistry , Peptides/chemical synthesis , Fungi/drug effectsABSTRACT
Global warming has caused the degradation of coral reefs around the world. While stress-tolerant corals have demonstrated the ability to acclimatize to ocean warming, it remains unclear whether they can sustain their thermal resilience when superimposed with other coastal environmental stressors. We report the combined impacts of a photosystem II (PSII) herbicide, prometryn, and ocean warming on the stress-tolerant coral Galaxea fascicularis through physiological and omics analyses. The results demonstrate that the heat-stress-induced inhibition of photosynthetic efficiency in G. fascicularis is exacerbated in the presence of prometryn. Transcriptomics and metabolomics analyses indicate that the prometryn exposure may overwhelm the photosystem repair mechanism in stress-tolerant corals, thereby compromising their capacity for thermal acclimation. Moreover, prometryn might amplify the adverse effects of heat stress on key energy and nutrient metabolism pathways and induce a stronger response to oxidative stress in stress-tolerant corals. The findings indicate that the presence of prometryn at environmentally relevant concentrations would render corals more susceptible to heat stress and exacerbate the breakdown of coral Symbiodiniaceae symbiosis. The present study provides valuable insights into the necessity of prioritizing PSII herbicide pollution reduction in coral reef protection efforts while mitigating the effects of climate change.
Subject(s)
Anthozoa , Herbicides , Animals , Anthozoa/physiology , Prometryne , Coral Reefs , Oceans and Seas , SymbiosisABSTRACT
OBJECTIVE: To investigate the effect of vacuum extraction (VE) or caesarean section (CS), compared with expectant management, on pelvic floor dysfunction (PFD) 1-2 years postpartum in primiparous women with a prolonged second stage of labour. DESIGN: A population-based questionnaire and cohort study. SETTING: Stockholm, Sweden. POPULATION: A cohort of 1302 primiparous women with a second stage duration of ≥3 h, delivering from December 2017 to November 2018. METHODS: The 1-year follow-up questionnaire from the Swedish National Perineal Laceration Register was distributed 12-24 months postpartum. Exposure was VE or CS at 3-4 h or 4-5 h, compared with expectant management. MAIN OUTCOME MEASURES: Pelvic floor dysfunction was defined as at least weekly symptoms of urinary incontinence, pelvic organ prolapse or a Wexner score of ≥4. The risk of PFD was calculated using Poisson regression with robust variance estimation, presented as crude and adjusted relative risks (RRs and aRRs) with 95% confidence intervals (95% CIs). The implication of obstetric anal sphincter injury (OASI) on pelvic floor disorders was investigated through mediation analysis. RESULTS: In total, 35.1% of women reported PFD. Compared with expectant management, the risk of PFD was increased after VE at 3-4 h (aRR 1.33, 95% CI 1.06-1.65) and 4-5 h (aRR 1.34, 95% CI 1.05-1.70), but remained unchanged after CS. The increased risk after VE was not mediated by OASI. CONCLUSIONS: Pelvic floor dysfunction was common in primiparous women after a prolonged second stage, and the risk of PFD increased after VE but was unaffected by CS, compared with expectant management. If a spontaneous vaginal delivery eventually occurred, allowing an extended duration of labour did not increase the risk of PFD.
Subject(s)
Cesarean Section , Labor Stage, Second , Pelvic Floor Disorders , Vacuum Extraction, Obstetrical , Watchful Waiting , Humans , Female , Pregnancy , Adult , Pelvic Floor Disorders/etiology , Pelvic Floor Disorders/epidemiology , Pelvic Floor Disorders/therapy , Sweden/epidemiology , Vacuum Extraction, Obstetrical/adverse effects , Vacuum Extraction, Obstetrical/statistics & numerical data , Surveys and Questionnaires , Cesarean Section/statistics & numerical data , Cesarean Section/adverse effects , Cohort Studies , Obstetric Labor Complications/epidemiology , Obstetric Labor Complications/etiology , Pelvic Organ Prolapse/epidemiology , Pelvic Organ Prolapse/therapy , Pelvic Organ Prolapse/etiology , Urinary Incontinence/etiology , Urinary Incontinence/epidemiologyABSTRACT
Hepatocellular carcinoma (HCC) is a major challenge for human healthy. Daphnane-type diterpenes have attracted increasingly attention due to remarkable pharmaceutical potential including anti-HCC activity. To further develop this class of compounds as inhibitors of HCC, the daphnane diterpenoids 12-O-debenzoyl-Yuanhuacine (YHC) and 12-hydroxydaphnetoxin (YHE) were prepared by a standard chemical transformation from dried flower buds of the Daphne genkwa plant. Subsequently, 22 daphnane diterpenoidal 1,3,4-oxdiazole derivatives were rationally designed and synthesized based on YHC and YHE. The assessment of the target compound's anti-hepatocellular carcinoma activity revealed that YHC1 exhibited comparable activity to sorafenib in the Hep3B cell line, while demonstrating higher selectivity. The mechanistic investigation demonstrates that compound YHC1 induces cell cycle arrest at the G0/G1 phase, cellular senescence, apoptosis, and elevates cellular reactive oxygen species levels. Moreover, molecular docking and CETSA results confirm the interaction between YHC1 and YAP1 as well as TEAD1. Co-IP experiments further validated that YHC1 can effectively inhibit the binding of YAP1 and TEAD1. In conclusion, YHC1 selectively targets YAP1 and TEAD1, exhibiting its anti-hepatocellular carcinoma effects through the inhibition of their interaction.
Subject(s)
Carcinoma, Hepatocellular , Daphne , Diterpenes , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell Proliferation , Daphne/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Liver Neoplasms/drug therapy , Molecular Docking Simulation , Oxadiazoles/chemistry , Oxadiazoles/pharmacologyABSTRACT
Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.
Subject(s)
Cardiac Surgical Procedures , Cardiopulmonary Bypass , Practice Guidelines as Topic , Humans , Cardiopulmonary Bypass/methods , Cardiopulmonary Bypass/standards , Cardiac Surgical Procedures/methods , Practice Guidelines as Topic/standardsABSTRACT
PURPOSE: This study aims to analyse the effect of diabetes mellitus (DM) on the radiological changes of Magnetic Resonance Imaging (MRI) on the intervertebral discs and paravertebral muscle to investigate the effect of DM on spinal degeneration. METHODS: This retrospective study initially included 262 patients who underwent treatment between January 2020 and December 2021 because of lumbar disc herniation. Amongst these patients, 98 patients suffered from type 2 diabetes mellitus (T2DM) for more than five years; this is the poorly controlled group (haemoglobin A1c (HbA1c) ≥ 6.5%; BMI: 26.28 ± 3.60; HbA1c: 7.5, IQR = 1.3). Another 164 patients without T2DM are included in the control group. The data collected and analysed include gender, age, smoking, alcohol use, disease course, Charlson Comorbidity Index, BMI, and radiological parameters including disc height, modified Pfirrmann grading scores, percentage of fat infiltration area of paravertebral muscle, and pathological changes of the endplate. RESULTS: After propensity score-matched analysis, the difference in general data between the control and T2DM groups was eliminated, and 186 patients were analysed. The modified Pfirrmann grading scores showed statistical differences in every lumbar segment, suggesting that the T2DM group suffered from greater disc degeneration at all L1-S1 segments compared with the control group. The disc height from L1/2 to L5/S1 was not statistically different between the two groups. Compared to the T2DM group, the control group had a lower percentage of fat infiltration areas in L4/5 and L5/S1 paravertebral muscle, whereas L1/2 to L3/4 showed no statistical difference. The T2DM group had more pathological changes of cartilage endplate compared with the control group. CONCLUSIONS: Prolonged uncontrolled hyperglycaemia may contribute to lumbar disc degeneration, fatty infiltration of the paraspinal muscles in the lower lumbar segments, and increased incidence of endplate cartilage pathological changes in patients with degenerative disc disease.
Subject(s)
Diabetes Mellitus, Type 2 , Intervertebral Disc Degeneration , Lumbar Vertebrae , Magnetic Resonance Imaging , Humans , Intervertebral Disc Degeneration/diagnostic imaging , Male , Female , Middle Aged , Magnetic Resonance Imaging/methods , Lumbar Vertebrae/diagnostic imaging , Diabetes Mellitus, Type 2/diagnostic imaging , Diabetes Mellitus, Type 2/complications , Retrospective Studies , Adult , Aged , Intervertebral Disc Displacement/diagnostic imagingABSTRACT
Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.
Subject(s)
Antiviral Agents , Influenza A virus , Mycophenolic Acid , Orthomyxoviridae Infections , Virus Replication , Animals , Antiviral Agents/pharmacology , Influenza A virus/drug effects , Mycophenolic Acid/pharmacology , Mice , Virus Replication/drug effects , Humans , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Mice, Inbred BALB C , Dogs , Female , Madin Darby Canine Kidney Cells , A549 Cells , Aquatic Organisms , Influenza, Human/drug therapy , Influenza, Human/virologyABSTRACT
Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.
Subject(s)
Metabolomics , Molecular Docking Simulation , Network Pharmacology , Peristalsis , Zingiber officinale , Zingiber officinale/chemistry , Metabolomics/methods , Animals , Peristalsis/drug effects , Male , Diarrhea/drug therapy , Plant Extracts/pharmacology , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Metabolome/drug effects , Metabolome/physiology , Intestines/drug effectsABSTRACT
BACKGROUND: Acute mesenteric ischemia is a rare but lethal disease. Acute occlusive mesenteric ischemia consists of mesenteric artery embolism, mesenteric artery thrombosis, and mesenteric vein thrombosis. This study aimed to investigate the factors that may affect the outcome of acute occlusive mesenteric ischemia. METHODS: Data from acute occlusive mesenteric ischemia patients admitted between May 2016 and May 2022 were reviewed retrospectively. Patients were divided into 2 groups according to whether complications(ClavienâDindo ≥ 2) occurred within 6 months of the first admission. Demographics, symptoms, signs, laboratory results, computed tomography angiography features, management and outcomes were analyzed. RESULTS: 59 patients were enrolled in this study. Complications(ClavienâDindo ≥ 2) occurred within 6 months of the first admission in 17 patients. Transmural intestinal necrosis, peritonitis, white blood cell count, percentage of neutrophils, percentage of lymphocytes, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, creatine kinase isoenzyme, cardiac troponin I, laparoscopic exploration rate, open embolectomy rate, enterostomy rate, length of necrotic small bowel, length of healthy small bowel, surgical time and intraoperative blood loss differed significantly between groups. Creatine kinase isoenzyme (OR = 1.415, 95% CI: 1.060-1.888) and surgical time (OR = 1.014, 95% CI: 1.001-1.026) were independent risk factors associated with complications(ClavienâDindo ≥ 2). CONCLUSIONS: Our analysis suggests that acute occlusive mesenteric ischemia patients with a creatine kinase isoenzyme level greater than 2.22 ng/mL or a surgical time longer than 156 min are more likely to experience complications'(ClavienâDindo ≥ 2) occurrence within 6 months of the first admission.
Subject(s)
Mesenteric Ischemia , Mesenteric Vascular Occlusion , Thrombosis , Humans , Mesenteric Ischemia/etiology , Mesenteric Ischemia/surgery , Retrospective Studies , Isoenzymes , Acute Disease , Ischemia/etiology , Creatine Kinase , Mesenteric Vascular Occlusion/complications , Mesenteric Vascular Occlusion/diagnosis , Mesenteric Vascular Occlusion/surgeryABSTRACT
INTRODUCTION: Qi-Fu-Yin has been used to treat Alzheimer's disease (AD) in China. Oxidative stress has been recognized as a factor in AD progress. To date, there is no quality control method to ensure batch-to-batch consistency of Qi-Fu-Yin, and the potential antioxidant compounds in Qi-Fu-Yin remain uncertain. OBJECTIVES: The aim of this study is to identify the potential antioxidant compounds of Qi-Fu-Yin and establish quality control standards for Qi-Fu-Yin. METHODS: High-performance liquid chromatography was used to establish and quantify the fingerprints of Qi-Fu-Yin from various batches. Ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the common peaks. Bivariate correlation analysis, partial least squares regression analysis, and gray correlation analysis were used to establish the spectrum-effect relationship. RESULTS: Forty-nine common peaks were determined through the establishment of fingerprints. Among them, 35 common peaks were preliminarily characterized. The multiple statistical correlation analysis methods identified six compounds as potential antioxidant constituents of Qi-Fu-Yin, and their antioxidant activities were validated in vitro. All six antioxidant compounds derived from two herbs. Therefore, three chemical index compounds derived from other three herbs were added to the quantitative analysis, while for two herbs, no peaks could be included. Eventually, six antioxidant constituents and three index compounds were quantitatively determined to provide a relatively comprehensive quality control for Qi-Fu-Yin. CONCLUSIONS: The study elucidated the antioxidant substance basis of Qi-Fu-Yin and provided a relatively comprehensive approach for the assay of Qi-Fu-Yin, which is a promising advance in the quality control of Qi-Fu-Yin.
ABSTRACT
In this paper, an electro-hydraulic servo resonance technology is proposed to meet the loading requirements of a high-frequency sound fatigue test for large tonnage. First of all, we analyze the static and dynamic loading structure of electro-hydraulic servo vibration and establish the vibration equation of the system. Additionally, the modal and vibration characteristics of the system are analyzed by simulation, which verified the feasibility of the proposed electro-hydraulic servo resonant loading technology. Finally, the influence of various factors such as sample stiffness, lead screw stiffness, class II spring stiffness, class II weight mass, lower beam mass, and upper beam mass on the natural frequency and amplification coefficient of the system is analyzed. In this paper, a new technology is proposed to provide theoretical support for the research and development of large-tonnage high-frequency noise fatigue testing equipment.
ABSTRACT
The objective of this article is to examine potential techniques for suppressing solar heat flow on the optical antenna of a laser communication sensor. Firstly, the characteristics of the geosynchronous Earth orbit's (GEO) space radiation environment are analysed, and a combined passive and active thermal control solution is proposed. Secondly, the temperature distribution of the lasercom sensor under extreme operating conditions is simulated utilising IDEAS-TMG (6.8 NX Series) software, which employs Monte Carlo and radiative heat transfer numerical calculation methods. Finally, a strategy for avoiding direct sunlight around midnight is proposed. The simulation results demonstrated that the thermal control solution and solar avoidance strategy proposed in this paper achieved long-term fine-stable control of the temperature field of the optical antenna, which met the thermal permissible communication hours per daily orbit cycle in excess of 14 h per day.
ABSTRACT
Aiming at the shortcomings of single-sensor sensing information characterization ability, which is easily interfered with by external environmental factors, a method of intelligent perception is proposed in this paper. This method integrates multi-source and multi-level information, including spindle temperature field, spindle thermal deformation, operating parameters, and motor current. Firstly, the internal and external thermal-error-related signals of the spindle system are collected by sensors, and the feature parameters are extracted; then, the radial basis function (RBF) neural network is utilized to realize the preliminary integration of the feature parameters because of the advantages of the RBF neural network, which offers strong multi-dimensional solid nonlinear mapping ability and generalization ability. Thermal-error decision values are then generated by a weighted fusion of different pieces of evidence by considering uncertain information from multiple sources. The spindle thermal-error sensing experiment was based on the spindle system of the VMC850 (Yunnan Machine Tool Group Co., LTD, Yunnan, China) vertical machining center of the Yunnan Machine Tool Factory. Experiments were designed for thermal-error sensing of the spindle under constant speed (2000 r/min and 4000 r/min), standard variable speed, and stepped variable speed conditions. The experiment's results show that the prediction accuracy of the intelligent-sensing model with multi-source information fusion can reach 98.1%, 99.3%, 98.6%, and 98.8% under the above working conditions, respectively. The intelligent-perception model proposed in this paper has higher accuracy and lower residual error than the traditional BP neural network perception and wavelet neural network models. The research in this paper provides a theoretical basis for the operation, maintenance management, and performance optimization of machine tool spindle systems.