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INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.
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Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.
Subject(s)
Apoptosis , Cyclooctanes , Lignans , Lipopolysaccharides , Polycyclic Compounds , Sertoli Cells , Animals , Male , Cyclooctanes/pharmacology , Polycyclic Compounds/pharmacology , Polycyclic Compounds/therapeutic use , Lignans/pharmacology , Lignans/therapeutic use , Apoptosis/drug effects , Mice , Sertoli Cells/drug effects , Sertoli Cells/metabolism , Receptors, Androgen/metabolism , MAP Kinase Signaling System/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Molecular Docking Simulation , Testis/drug effects , Testis/metabolism , Testis/pathology , NF-kappa B/metabolismABSTRACT
BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.
Subject(s)
Embolization, Therapeutic , Image-Guided Biopsy , Lung , Pneumothorax , Pulmonary Emphysema , Tomography, X-Ray Computed , Humans , Pneumothorax/etiology , Pneumothorax/prevention & control , Pneumothorax/epidemiology , Female , Male , Retrospective Studies , Aged , Middle Aged , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/methods , Embolization, Therapeutic/methods , Lung/pathology , Lung/diagnostic imaging , Risk Factors , Logistic Models , Chest Tubes , Gelatin Sponge, Absorbable/administration & dosage , Incidence , Multivariate Analysis , Aged, 80 and over , Radiography, Interventional/methodsABSTRACT
The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.
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Adenoviridae , Oncolytic Virotherapy , Oncolytic Viruses , Virus Replication , Animals , Oncolytic Virotherapy/methods , Adenoviridae/genetics , Adenoviridae/physiology , Oncolytic Viruses/physiology , Oncolytic Viruses/genetics , Virus Replication/radiation effects , Mice , Humans , Cell Line, Tumor , Ultrasonic Therapy/methods , Melanoma/therapy , Melanoma/pathologyABSTRACT
BACKGROUND AND PURPOSE: Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a non-invasive prediction model for meningioma consistency utilizing magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Ninety-four patients (52yr ± 22, 69 females, 25 males) diagnosed with meningioma were recruited in the study. Each patient underwent preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), DTI, and MRE. Combined MRE-DTI model was developed based on multiple logistic regression. Intraoperative tumor descriptions served as clinical criteria for evaluating meningioma consistency. The diagnostic efficacy in determining meningioma consistency was evaluated using receiver operating characteristic (ROC) curve. Further validation was conducted in twenty-seven stereotactic biopsies using indentation tests and underlying mechanism was investigated by histologic analysis. RESULTS: Among all the imaging modalities, MRE demonstrated the highest efficacy with the shear modulus magnitude (|G*|) achieving an area under the curve (AUC) of 0.81 (95% CI: 0.70-0.93). When combined with DTI, the diagnostic accuracy further increased (AUC: 0.88, 95% CI: 0.78-0.97), surpassing any modality alone. Indentation measurement based on stereotactic biopsies further demonstrated that the MRE-DTI model was suitable for predicting intra-tumor consistency. Histological analysis suggested that meningioma consistency may be correlated with tumor cell density and fibrous content. CONCLUSIONS: The MRE-DTI combined model is effective in noninvasive prediction of meningioma consistency. ABBREVIATIONS: MRE = magnetic resonance elastography; FA = fractional anisotropy; ROC = receiver operating characteristic; AUC = area under curve.
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OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.
Subject(s)
Cervical Vertebrae , Decompression, Surgical , Dura Mater , Ossification of Posterior Longitudinal Ligament , Tomography, X-Ray Computed , Humans , Ossification of Posterior Longitudinal Ligament/surgery , Ossification of Posterior Longitudinal Ligament/diagnostic imaging , Male , Female , Middle Aged , Aged , Tomography, X-Ray Computed/methods , Dura Mater/surgery , Dura Mater/diagnostic imaging , Decompression, Surgical/methods , Retrospective Studies , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Adult , Risk FactorsABSTRACT
BACKGROUND: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. OBJECTIVE: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. METHODS: In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. RESULTS: The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. CONCLUSIONS: In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.
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Big Data , Data Mining , Drug-Related Side Effects and Adverse Reactions , Humans , Data Mining/methods , Pharmacovigilance , Models, Theoretical , Adverse Drug Reaction Reporting Systems/statistics & numerical dataABSTRACT
The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.
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Hydrogels , Macrophages , Regeneration , Wound Healing , Hydrogels/chemistry , Macrophages/immunology , Macrophages/drug effects , Humans , Animals , Regeneration/immunology , Wound Healing/drug effects , Wound Healing/immunology , Tissue Engineering , Immunomodulation/drug effectsABSTRACT
Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.
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This article reports the preparation of multifunctional magnetic nanocomposite hydrogels formed from wormlike micelles. Specifically, iron oxide nanoparticles were incorporated into a temperature responsive block copolymer, poly(glycerol monomethacrylate)-b-poly(2-hydroxypropyl methacrylate) (PGMA-b-PHPMA), and graphene oxide (GO) dispersion at a low temperature (â¼2 °C) through high-speed mixing and returning the mixture to room temperature, resulting in the formation of nanocomposite gels. The optimal concentrations of iron oxide and GO enhanced the gel strength of the nanocomposite gels, which exhibited a strong magnetic response when a magnetic field was applied. These materials retained the thermoresponsiveness of the PGMA-PHPMA wormlike micelles allowing for a solid-to-liquid transition to occur when the temperature was reduced. The mechanical and rheological properties and performance of the nanocomposite gels were demonstrated to be adjustable, making them suitable for a wide range of potential applications. These nanocomposite worm gels were demonstrated to be relatively adhesive and to act as strain and temperature sensors, with the measured electrical resistance of the nanocomposite gels changing with applied strain and temperature sweeps. The nanocomposite gels were found to recover efficiently after the application of high shear with approximately 100% healing efficiency within seconds. Additionally, these nanocomposite worm gels were injectable, and the addition of GO and iron oxide nanomaterials seemed to have no significant adverse impact on the biocompatibility of the copolymer gels, making them suitable not only for 3D printing in nanocomposite engineering but also for potential utilization in various biomedical applications as an injectable magnetic responsive hydrogel.
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Aiming at the multi-attribute bilateral matching problem with unknown attribute weights under a linguistic intuitionistic fuzzy environment, a decision method based on TODIM considering satisfaction and fairness degrees is proposed. First, the theories of linguistic intuitionistic fuzzy sets and bilateral matching are given, and the multi-attribute bilateral matching problem under a linguistic intuitionistic fuzzy environment is described. To solve this problem, according to linguistic intuitionistic fuzzy preference matrices, the overall attribute dominances are calculated based on TODIM; considering group consensus, a new method is proposed to calculate attribute weights based on linguistic intuitionistic fuzzy induced ordered weighted averaging (LIFIOWA) operator; then, the overall dominances of bilateral subjects are obtained by aggregating the overall attribute dominances and attribute weights. Furthermore, the overall dominances are standardized to calculate the satisfaction degrees of bilateral subjects; the fairness degrees of bilateral subjects are calculated considering the loss attenuation coefficient. Based on satisfaction degree matrices, fairness degree matrices and bilateral matching matrices, multiple bilateral matching models are established and then solved to obtain the optimal bilateral matching scheme. Finally, an example shows the effectiveness, reliability and accuracy of the proposed method. The research results indicate the following main characteristics of the proposed method: (1) A new method for calculating the unknown attribute weights using LIFIOWA operator is proposed. (2) According to the TODIM idea, a calculation method for fairness degree considering the loss attenuation coefficient is proposed. (3) Considering satisfaction and fairness degrees, multiple bilateral matching models under a linguistic intuitionistic fuzzy environment are established.
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Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.
Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Saponins , Signal Transduction , Triterpenes , Animals , Humans , Male , Mice , Blood Glucose/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Hippocampus/drug effects , Hippocampus/metabolism , Mice, Inbred C57BL , Neurons/drug effects , Neurons/metabolism , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Saponins/pharmacology , Saponins/administration & dosage , Signal Transduction/drug effects , Triterpenes/pharmacology , Triterpenes/administration & dosageABSTRACT
There is a high demand for rapid, sensitive, and accurate detection methods for pathogens. This paper demonstrates a method of detecting the presence of amplified DNA from a range of pathogens associated with serious infections including Gram-negative bacteria, Gram-positive bacteria, and viruses. DNA is amplified using a polymerase chain reaction (PCR) and consequently detected using a sterically stabilized, cationic polymer latex. The DNA induces flocculation of this cationic latex, which consequently leads to rapid sedimentation and a visible change from a milky-white dispersion to one with a transparent supernatant, presenting a clear visible change, indicating the presence of amplified DNA. Specifically, a number of different pathogens were amplified using conventional or qPCR, including Staphylococcus aureus, Escherichia coli, and Herpes Simplex Virus (HSV-2). This method was demonstrated to detect the presence of bacteria in suspension concentrations greater than 380 CFU mL-1 and diagnose the presence of specific genomes through primer selection, as exemplified using methicillin resistant and methicillin susceptible Staphylococcus aureus. The versatility of this methodology was further demonstrated by showing that false positive results do not occur when a PCR of fungal DNA from C. albicans is conducted using bacterial universal primers.
Subject(s)
Biosensing Techniques , Latex , Flocculation , DNA/genetics , Staphylococcus aureus/genetics , Polymerase Chain Reaction/methods , DNA, Bacterial/genetics , Sensitivity and SpecificityABSTRACT
The crisp grass carp (CGC; Ctenopharyngodon idellus C. et V.), known for its unique texture and flavour, is a culinary delicacy whose quality is significantly influenced by thermal processing. This study employed 4D label-free proteomics and data mining techniques to investigate the proteomic changes in CGC muscle tissue induced by various heating temperatures. CGC samples were subjected to a series of heat treatments at increasing temperatures from 20 °C to 90 °C. Proteins were extracted, digested, and analysed using high-resolution mass spectrometry. The proteomic data were then subjected to extensive bioinformatics analysis, including GO and KEGG pathway enrichment. We identified a total of 1085 proteins, 516 of which were shared across all the temperature treatments, indicating a core proteome responsible for CGC textural properties. Differential expression analysis revealed temperature-dependent changes, with significant alterations observed at 90 °C, suggesting denaturation or aggregation of proteins at higher temperatures. Functional enrichment analysis indicated that proteins involved in amino acid metabolism, glutathione metabolism, and nucleotide metabolism were particularly affected by heat. Textural analysis correlated these proteomic changes with alterations in CGC quality attributes, pinpointing 70 °C as the optimum temperature for maintaining the desired texture. A strong positive correlation between specific upregulated proteins was identified, such as the tubulin alpha chain and collagen alpha-1(IV) chain, and the improved textural properties of CGC during thermal processing, suggesting their potential as the potential biomarkers. This study offers a comprehensive proteomic view of the thermal stability and functionality of CGC proteins, delivering invaluable insights for both the culinary processing and scientific management of CGC. Our findings not only deepen the understanding of the molecular mechanisms underpinning the textural alterations in CGC during thermal processing but also furnish practical insights for the aquaculture industry. These insights could be leveraged to optimize cooking techniques, thereby enhancing the quality and consumer appeal of CGC products.
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Poly(glycerol monomethacrylate) (PGMA) prepared by reversible addition-fragmentation chain transfer polymerization was investigated as an additive for high-loading iron oxide nanoparticle (IOP) 3D printable inks. The effect of adjusting the molar mass and loading of PGMA on the rheology of IOP suspensions was investigated, and an optimized ink formulation containing 70% w/w IOPs and 0.25% w/w PGMA98 at pH 10 was developed. This ink was successfully 3D printed onto various substrates and into several structures, including rectangles, high aspect ratio cylinders, letters, spiral- and comb-shaped structures, and thin- and thick-walled toroids. The effect of sintering on the mechanical properties of printed artifacts was investigated via four-point flexural and compressive testing, with higher sintering temperatures resulting in improved mechanical properties due to changes in the particle size and microstructure. The printed toroids were fabricated into inductors, and their electrical performance was assessed via impedance spectroscopy at a working frequency range of 0.001-13 MHz. There was a clear trade-off between electrical properties and sintering temperature due to a phase change between γ-Fe2O3 and α-Fe2O3 upon heating. Nevertheless, the optimized devices had a Q factor of â¼40 at 10 MHz, representing a superior performance compared to that of other inductors with iron oxide cores previously reported. Thus, this report represents a significant step toward the development of low-cost, fully aqueous, high loading, and 3D printable ceramic inks for high-performance inductors and functional devices.
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In view of the fact that people pay more and more attention to the principle of "getting the position according to the person" and "adapting the person to the position" in person-position matching, a dynamic person-position matching decision method based on hesitant fuzzy numbers is proposed. First, the dynamic person-position matching problem with hesitant fuzzy numbers is described. Then, according to hesitant fuzzy evaluation matrices of positions and candidates, expected score matrices of bilateral subjects are calculated. Furthermore, based on the idea of the generalized optimal order method and the dominant correlation and the missing correlation coefficients, satisfaction means of people and positions are calculated. According to satisfaction means, growth satisfactions at each period are obtained, and then the exponential decay formula is used to determine weights of growth satisfactions. Dynamic satisfactions of bilateral subjects are calculated by aggregating initial satisfaction means and growth satisfactions. On this basis, a stable person-position matching model considering dynamic satisfactions is established and then is solved to obtain the optimal stable person-position matching scheme. Finally, the feasibility and effectiveness of the proposed method are verified by an example analysis of person-position matching. Main contributions of this paper are as follows: an effective calculation method for the missing correlation coefficient is presented; a novel effective calculation method for dynamic satisfactions is proposed by introducing the correlation parameter to combine the missing correlation coefficient with the dominant correlation coefficient; an effective stable person-position matching model considering dynamic satisfactions is established.
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Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral-biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)-based nanoparticles (NPs) are integrated into poly(D, L-lactide)-poly(ethylene glycol)-poly(D, L-lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self-assembled ChS and ε-poly-l-lysine (EPL) NPs are prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in interleukin-1ß (IL-1ß)-mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS-based hydrogel system offers a potential strategy to regulate the chondrocyte-macrophage crosstalk, thus re-establishing the anti-inflammatory and immunomodulatory microenvironment for OA therapy.
Subject(s)
Chondrocytes , Chondroitin Sulfates , Homeostasis , Nanoparticles , Osteoarthritis , Osteoarthritis/pathology , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Animals , Chondrocytes/metabolism , Chondrocytes/drug effects , Homeostasis/drug effects , Nanoparticles/chemistry , Chondroitin Sulfates/chemistry , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/pharmacology , Mice , Hydrogels/chemistry , Bionics , RAW 264.7 Cells , Male , Drug Delivery Systems/methods , Humans , Rats , Rats, Sprague-Dawley , Cartilage, Articular/pathology , Cartilage, Articular/drug effects , Cartilage, Articular/metabolismABSTRACT
BACKGROUND: Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a devastating bacterial disease that reduces citrus yield and quality, posing a serious threat to the citrus industry. Several conventional chemicals have been used to control citrus canker. However, this approach often leads to the excessive use of chemical agents, can exacerbate environmental pollution and promotes the development of resistant Xcc. Therefore, there is significant interest in the development of efficient and environmentally friendly technologies to control citrus canker. RESULTS: In this study, water-soluble ZnO quantum dots (ZnO QDs) were synthesised as an efficient nanopesticide against Xcc. The results showed that the antibacterial activity of ZnO QDs irradiated with visible light [half-maximal effective concentration (EC50) = 33.18 µg mL-1] was ~3.5 times higher than that of the dark-treated group (EC50 = 114.80 µg mL-1). ZnO QDs induced the generation of reactive oxygen species (â¢OH, â¢O- 2 and 1O2) under light irradiation, resulting in DNA damage, cytoplasmic destruction, and decreased catalase and superoxide dismutase activities. Transcription analysis showed downregulation of Xcc genes related to 'biofilms, virulence, adhesion' and 'DNA transfer' exposure to ZnO QDs. More importantly, ZnO QDs also promoted the growth of citrus. CONCLUSION: This research provides new insights into the photocatalytic antibacterial mechanisms of ZnO QDs and supports the development of more efficient and safer ZnO QDs-based nanopesticides to control citrus canker. © 2024 Society of Chemical Industry.
Subject(s)
Citrus , Light , Plant Diseases , Quantum Dots , Xanthomonas , Zinc Oxide , Quantum Dots/chemistry , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Xanthomonas/drug effects , Xanthomonas/radiation effects , Plant Diseases/microbiology , Plant Diseases/prevention & control , Citrus/microbiology , Anti-Bacterial Agents/pharmacologyABSTRACT
During nuclear accidents, large amounts of short-lived radionuclides are released into the environment, causing acute health hazards to local populations. Therefore, it is particularly important to obtain source-term information to assist nuclear emergency decision makers in determining emergency protective measures. However, it is extremely difficult to obtain reliable contaminant monitoring instrument readings to estimate the source term based on core conditions, release routes, and release conditions. Currently, a wide variety of source-term inversion methods are attracting increasing attention. In this study, the release rates of four typical short-lived nuclides (Kr-88, Sr-91, Te-132, I-131) in two complex nuclear accident scenarios were estimated using a machine-learning method. The results show that the best estimation performance is obtained with the long short-term memory network, and the mean absolute percentage errors for the release rates of the four nuclides at 10 h under the two nuclear accidents are 9.87% and 11.08%, 17.49% and 16.51%, 7.16% and 8.35%, and 38.83% and 41.87%, respectively. Meanwhile, the mean absolute percentage errors for Te-132 (7.16% and 8.35%) were the lowest among all the estimated nuclides. In addition, stability analysis showed that the gamma dose rate was the key parameter affecting the estimation accuracy.
ABSTRACT
In recent years, along with the rapid development in the domain of artificial intelligence and aerospace, aerospace combined with artificial intelligence is the future trend. As an important basic tool for Natural Language Processing, Named Entity Recognition technology can help obtain key relevant knowledge from a large number of aerospace data. In this paper, we produced an aerospace domain entity recognition dataset containing 30 k sentences in Chinese and developed a named entity recognition model that is Multi-Feature Fusion Transformer (MFT), which combines features such as words and radicals to enhance the semantic information of the sentences. In our model, the double Feed-forward Neural Network is exploited as well to ensure MFT better performance. We use our aerospace dataset to train MFT. The experimental results show that MFT has great entity recognition performance, and the F1 score on aerospace dataset is 86.10%.