ABSTRACT
Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health-promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome. However, incorporating soluble fiber inulin, but not insoluble fiber, into a compositionally defined diet, induced icteric hepatocellular carcinoma (HCC). Such HCC was microbiota-dependent and observed in multiple strains of dysbiotic mice but not in germ-free nor antibiotics-treated mice. Furthermore, consumption of an inulin-enriched high-fat diet induced both dysbiosis and HCC in wild-type (WT) mice. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by neutrophilic inflammation in liver. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent reabsorption of bile acids also conferred protection against such HCC. Thus, its benefits notwithstanding, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC.
Subject(s)
Carcinoma, Hepatocellular/etiology , Cholestasis/complications , Dietary Fiber/metabolism , Dysbiosis/complications , Fermentation , Gastrointestinal Microbiome , Liver Neoplasms/etiology , Animals , Carcinoma, Hepatocellular/microbiology , Cell Line, Tumor , Cholestasis/microbiology , Diet, High-Fat/adverse effects , Dysbiosis/microbiology , Inulin/adverse effects , Liver Neoplasms/microbiology , Male , Mice , Mice, Inbred C57BLABSTRACT
Grain size is an important agronomic trait, but our knowledge about grain size determination in crops is still limited. Endoplasmic reticulum (ER)-associated degradation (ERAD) is a special ubiquitin proteasome system that is involved in degrading misfolded or incompletely folded proteins in the ER. Here, we report that SMALL GRAIN 3 (SMG3) and DECREASED GRAIN SIZE 1 (DGS1), an ERAD-related E2-E3 enzyme pair, regulate grain size and weight through the brassinosteroid (BR) signaling pathway in rice (Oryza sativa). SMG3 encodes a homolog of Arabidopsis (Arabidopsis thaliana) UBIQUITIN CONJUGATING ENZYME 32, which is a conserved ERAD-associated E2 ubiquitin conjugating enzyme. SMG3 interacts with another grain size regulator, DGS1. Loss of function of SMG3 or DGS1 results in small grains, while overexpression of SMG3 or DGS1 leads to long grains. Further analyses showed that DGS1 is an active E3 ubiquitin ligase and colocates with SMG3 in the ER. SMG3 and DGS1 are involved in BR signaling. DGS1 ubiquitinates the BR receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) and affects its accumulation. Genetic analysis suggests that SMG3, DGS1, and BRI1 act together to regulate grain size and weight. In summary, our findings identify an ERAD-related E2-E3 pair that regulates grain size and weight, which gives insight into the function of ERAD in grain size control and BR signaling.
Subject(s)
Endoplasmic Reticulum-Associated Degradation , Oryza , Ubiquitin-Conjugating Enzymes , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Brassinosteroids/metabolism , Endoplasmic Reticulum-Associated Degradation/genetics , Oryza/genetics , Oryza/metabolism , Signal Transduction , Ubiquitin-Conjugating Enzymes/genetics , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Neuroinflammation mediated by microglia plays an important role in the etiology of Parkinson's disease (PD). Rho family GTPase 3 (RND3) exerts anti-inflammatory effects and may act as a potential new inducer of neuroprotective phenotypes in microglia. However, whether RND3 can be used to regulate microglia activation or reduce neuroinflammation in PD remains elusive. The study investigated the microglia modulating effects and potential anti-inflammatory effects of RND3 in vivo and in vitro, using animal models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and cell models of BV-2 cells stimulated by LPS plus IFN-γ with or without RND3-overexpression. The results showed that RND3 was highly expressed in the MPTP-induced PD mouse model and BV-2 cells treated with LPS and IFN-γ. In vivo experiments confirmed that RND3 overexpression could modulate microglia phenotype and ameliorate MPTP-induced neuroinflammation through inhibiting activation of the NLRP3 inflammasome in substantia nigra pars compacta (SNpc). In vitro study showed that RND3 overexpression could attenuate the production of pro-inflammatory factors in BV2 cells stimulated by LPS and IFN-γ. Mechanistically, RND3 reduced the activation of the NLRP3 inflammasome upon LPS and IFN-γ stimulation. Taken together, these findings suggest that RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.
Subject(s)
Inflammasomes , Mice, Inbred C57BL , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Parkinson Disease , rho GTP-Binding Proteins , Animals , Microglia/metabolism , Microglia/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Mice , Inflammasomes/metabolism , Male , rho GTP-Binding Proteins/metabolism , rho GTP-Binding Proteins/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Parkinson Disease/genetics , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , Lipopolysaccharides/pharmacology , Disease Models, Animal , Cell Polarity , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Inflammation/metabolism , Inflammation/pathology , Inflammation/genetics , Interferon-gamma/metabolismABSTRACT
Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1ß, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.
Subject(s)
Brain Ischemia , Drugs, Chinese Herbal , Rats, Sprague-Dawley , Synapses , Animals , Drugs, Chinese Herbal/pharmacology , Rats , Male , Synapses/drug effects , Synapses/metabolism , Brain Ischemia/metabolism , Brain Ischemia/drug therapy , Disease Models, Animal , GABAergic Neurons/metabolism , GABAergic Neurons/drug effects , gamma-Aminobutyric Acid/metabolism , Infarction, Middle Cerebral Artery/complications , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/complications , Neuroprotective Agents/pharmacology , Brain/pathology , Brain/metabolism , Brain/drug effectsABSTRACT
Peptide self-assemblies could leverage their specificity, stability, biocompatibility, and electrochemical activity to create functionalized interfaces for molecular sensing and detection. However, the dynamics within these interfaces are complex, with competing forces, including those maintaining peptide structures, recognizing analytes, and facilitating signal transmission. Such competition could lead to nonspecific interference, compromising the detection sensitivity and accuracy. In this study, a series of peptides with precise structures and controllable electron transfer capabilities were designed. Through examining their stacking patterns, the interplay between the peptides' hierarchical structures, their ability to recognize targets, and their conductivity were clarified. Among these, the EP5 peptide assembly was identified for its ability to form controllable electronic tunnels facilitated by π-stacking induced ß-sheets. EP5 could enhance the long-range conductivity, minimize nonspecific interference, and exhibit targeted recognition capabilities. Based on EP5, an electrochemical sensing interface toward the disease marker PD-L1 (programmed cell death ligand 1) was developed, suitable for both whole blood assay and in vivo companion diagnosis. It opens a new avenue for crafting electrochemical detection interfaces with specificity, sensitivity, and compatibility.
Subject(s)
Electrochemical Techniques , Electrochemical Techniques/methods , Humans , Protein Conformation, beta-Strand , Peptides/chemistry , B7-H1 Antigen/analysis , B7-H1 Antigen/blood , Electrons , AnimalsABSTRACT
Artificial solid-state nanochannels featuring precise partitions present a highly promising platform for biomarker detection. While the significance of probes on the outer surface (POS) has been relatively overlooked in the past, our research highlights their crucial role in biosensing. Furthermore, the contribution of POS on the bullet-shaped asymmetric nanochannels has not been extensively explored until now. Here, we fabricated a series of bullet-shaped nanochannels, each featuring a distinct asymmetric structure characterized by different tip- and base-pore diameters. These nanochannels were further modified with explicit distributions at the inner wall (PIW), the outer surface (POS), and their combination (POS + PIW) for lysozyme sensing. The impact of diameters, structural asymmetry, and surface charge density on the sensing efficacy of POS and PIW was thoroughly examined through experimental investigations and numerical simulations. POS demonstrates great individual sensing performance for lysozyme within a broad concentration range, spanning from 10 nM to 1 mM. Furthermore, it improves the sensitivity when combined with PIW, particularly within the nanochannels featuring the smaller base-pore diameter, resulting in a 2-fold increase in sensing performance for POS + PIW compared to PIW at a concentration of 10 nM. These findings are substantiated by numerical simulations that closely align with the experimental parameters. The contributions of POS are notably amplified in the presence of smaller base pores and a higher degree of asymmetry within the bullet-shaped nanochannels. These findings elucidate the mechanism underlying the role of POS within bullet-shaped asymmetric nanochannels and open up new avenues for manipulating and enhancing the sensing efficiency.
Subject(s)
Nanostructures , Nanostructures/chemistry , Muramidase , ProteinsABSTRACT
The construction of coassembled peptide nanoprobes based on structural adaptation provides an effective template for stable monitoring of the molecular events in physiological and pathological processes. This also greatly expands their applications in biomedicine, such as multimodal combined diagnosis and treatment. However, the insufficient understanding of the physicochemical properties and structural features of different molecules still makes it difficult to construct the coassembled probes with mutually reinforcing functions, leading to unpredictable effects. Here, we showed how to utilize the π-π stacking network on ß-sheets formed by PD-L1-targeting peptides to capture small molecules with ferroptosis functions, thus, coassembling them into a visual probe with synergistic effects. Compared with individual components, the coassembled strategy could significantly improve the stability of the nanoprobe, inducing stronger ferroptosis effects and immune checkpoint blocking effects, and track and reflect the process. This study provides new insights into the design of multicomponent collaborative coassembly systems with biological effects.
Subject(s)
Ferroptosis , Peptides , Ferroptosis/drug effects , Humans , Peptides/chemistry , B7-H1 Antigen/metabolism , B7-H1 Antigen/chemistry , Nanoparticles/chemistry , Fluorescent Dyes/chemistryABSTRACT
To reduce electromagnetic interference and noise pollution within communication base stations and servers, it is necessary for electromagnetic wave absorption (EWA) materials to transition from coating to multifunctional devices. Up to now, the stable and effective integration of multiple functions into one material by a simple method has remained a large challenge. Herein, a foam-type microwave absorption device assembled with multicomponent organic matter and graphite powder is synthesized by a universal combination process. Melamine and phenolic aldehyde amine work as the skeleton and cementing compound, respectively, in which graphite is embedded in the cementing compound interconnected into the mesoscopic 3D electric conductive and heat conductive network. Interestingly, the prepared flexible graphite/melamine foam (CMF) delivers a great EWA performance, with a great effective absorption bandwidth of 9.8 GHz, ultrathin thickness of 2.60 mm, and a strong absorption reflection loss of -41.7 dB. Moreover, the CMF possesses porosity and flexibility, endowing it with sound absorption ability. The CMF is unique in its integration of EWA, heat conduction, sound absorption, and mechanical robustness, as well as its cost-effective and scalable manufacturing. These attributes make CMF promising as a multifunctional device widely used in communication base stations, servers, and chips protection.
ABSTRACT
The direct application of liquid marbles in electromagnetic wave (EMW) absorption is challenging due to their poor stability, susceptibility to gravitational collapse, and shaping difficulties. To address this issue, a novel strategy is proposed to incorporate liquid marble microstructures (NaCl/nano-SiO2) encapsulated in organic phases (Octadecane) into the rubber-matrix (SEBS) using the ultrasound-assisted emulsion blending method. The resulting NaCl/SiO2/Octadecane microstructures anchored to SEBS offer a substantial solid-liquid interface consisting of NaCl solution and SiO2. When subjected to an alternating electromagnetic (EM) field, the water molecules and polysorbate within SiO2 exhibit heightened responsiveness to the EM field, and the movement of Na+ and Cl- within these microstructures leads to their accumulation at the solid-liquid interface, creating an asymmetric ion distribution. This phenomenon facilitates enhanced interfacial polarization, thereby contributing to the material's EMW absorption properties. Notably, the latex with 16 wt% SEBS (E-3), exhibiting a surface morphology similar to human cell tissues, achieves complete absorption of X-band (fE = 4.20 GHz, RLmin = -33.87 dB). Moreover, the latex demonstrates light density (0.78 g cm-3) and environmental stability. This study not only highlights the predominant loss mechanism in rubber-based wave-absorbing materials but also provides valuable insights into the design of multifunctional wave-absorbing materials.
ABSTRACT
Transition metals are excellent active sites to activate peroxymonosulfate (PMS) for water treatment, but the favorable electronic structures governing reaction mechanism still remain elusive. Herein, the authors construct typical d-orbital configurations on iron octahedral (FeOh ) and tetrahedral (FeTd ) sites in spinel ZnFe2 O4 and FeAl2 O4 , respectively. ZnFe2 O4 (136.58 min-1 F-1 cm2 ) presented higher specific activity than FeAl2 O4 (97.47 min-1 F-1 cm2 ) for tetracycline removal by PMS activation. Considering orbital features of charge amount, spin state, and orbital arrangement by magnetic spectroscopic analysis, ZnFe2 O4 has a larger bond order to decompose PMS. Using this descriptor, high-spin FeOh is assumed to activate PMS mainly to produce nonradical reactive oxygen species (ROS) while high-spin FeTd prefers to induce radical species. This hypothesis is confirmed by the selective predominant ROS of 1 O2 on ZnFe2 O4 and O2 â¢- on FeAl2 O4 via quenching experiments. Electrochemical determinations reveal that FeOh has superior capability than FeTd for feasible valence transformation of iron cations and fast interfacial electron transfer. DFT calculations further suggest octahedral d-orbital configuration of ZnFe2 O4 is beneficial to enhancing Fe-O covalence for electron exchange. This work attempts to understand the d-orbital configuration-dependent PMS activation to design efficient catalysts.
ABSTRACT
Exposure to triclocarban (TCC), a commonly used antibacterial agent, has been shown to induce significant intestine injuries and colonic inflammation in mice. However, the detailed mechanisms by which TCC exposure triggered enterotoxicity remain largely unclear. Herein, intestinal toxicity effects of long-term and chronic TCC exposure were investigated using a combination of histopathological assessments, metagenomics, targeted metabolomics, and biological assays. Mechanically, TCC exposure caused induction of intestinal aryl hydrocarbon receptor (AhR) and its transcriptional target cytochrome P4501A1 (Cyp1a1) leading to dysfunction of the gut barrier and disruption of the gut microbial community. A large number of lipopolysaccharides (LPS) are released from the gut lumen into blood circulation owing to the markedly increased permeability and gut leakage. Consequently, toll-like receptor-4 (TLR4) and NF-κB signaling pathways were activated by high levels of LPS. Simultaneously, classic macrophage phenotypes were switched by TCC, shown with marked upregulation of macrophage M1 and downregulation of macrophage M2 that was accompanied by striking upregulation of proinflammatory factors such as Il-1ß, Il-6, Il-17, and Tnf-α in the intestinal lamina propria. These findings provide new evidence for the TCC-induced enterotoxicity.
Subject(s)
Carbanilides , Lipopolysaccharides , Receptors, Aryl Hydrocarbon , Mice , Animals , Receptors, Aryl Hydrocarbon/metabolism , Lipopolysaccharides/toxicity , NF-kappa B/metabolism , Inflammation/metabolismABSTRACT
C-type lectins (CTLs) execute critical functions in multiple immune responses of crustaceans as a member of pattern recognition receptors (PRRs) family. In this study, a novel CTL was identified from the exoskeleton of the oriental river prawn Macrobrachium nipponense (MnLec3). The full-length cDNA of MnLec3 was 1150 bp with an open reading frame of 723 bp, encoding 240 amino acids. MnLec3 protein contained a signal peptide and one single carbohydrate-recognition domain (CRD). MnLec3 transcripts were widely distributed at the exoskeleton all over the body. Significant up-regulation of MnLec3 in exoskeleton after Aeromonas hydrophila challenged suggested the involvement of MnLec3 as well as the possible function of the exoskeleton in immune response. In vitro tests with recombinant MnLec3 protein (rMnLec3) manifested that it had polysaccharide binding activity, a wide spectrum of bacterial binding activity and agglutination activity only for tested Gram-negative bacteria (Escherichia coli, Vibrio anguillarum and A. hydrophila). Moreover, rMnLec3 significantly promoted phagocytic ability of hemocytes against A. hydrophila in vivo. What's more, MnLec3 interference remarkably impaired the survivability of the prawns when infected with A. hydrophila. Collectively, these results ascertained that MnLec3 derived from exoskeleton took an essential part in immune defense of the prawns against invading bacteria as a PRR.
Subject(s)
Aeromonas hydrophila , Amino Acid Sequence , Arthropod Proteins , Gene Expression Regulation , Hemocytes , Immunity, Innate , Lectins, C-Type , Palaemonidae , Phagocytosis , Phylogeny , Sequence Alignment , Animals , Palaemonidae/immunology , Palaemonidae/genetics , Lectins, C-Type/genetics , Lectins, C-Type/immunology , Lectins, C-Type/chemistry , Arthropod Proteins/genetics , Arthropod Proteins/immunology , Arthropod Proteins/chemistry , Hemocytes/immunology , Immunity, Innate/genetics , Aeromonas hydrophila/physiology , Sequence Alignment/veterinary , Gene Expression Regulation/immunology , Gene Expression Profiling/veterinary , Base Sequence , Animal Shells/immunology , Animal Shells/chemistryABSTRACT
Bioreduction of soluble U(VI) to sparingly soluble U(IV) is proposed as an effective approach to remediating uranium contamination. However, the stability of biogenic U(IV) in natural environments remains unclear. We conducted U(IV) reoxidation experiments following U(VI) bioreduction in the presence of ubiquitous clay minerals and organic ligands. Bioreduced Fe-rich nontronite (rNAu-2) and Fe-poor montmorillonite (rSWy-2) enhanced U(IV) oxidation through shuttling electrons between oxygen and U(IV). Ethylenediaminetetraacetic acid (EDTA), citrate, and siderophore desferrioxamine B (DFOB) promoted U(IV) oxidation via complexation with U(IV). In the presence of both rNAu-2 and EDTA, the rate of U(IV) oxidation was between those in the presence of rNAu-2 and EDTA, due to a clay/ligand-induced change of U(IV) speciation. However, the rate of U(IV) oxidation in other combinations of reduced clay and ligands was higher than their individual ones because both promoted U(IV) oxidation. Unexpectedly, the copresence of rNAu-2/rSWy-2 and DFOB inhibited U(IV) oxidation, possibly due to (1) blockage of the electron transport pathway by DFOB, (2) inability of DFOB-complexed Fe(III) to oxidize U(IV), and (3) stability of the U(IV)-DFOB complex in the clay interlayers. These findings provide novel insights into the stability of U(IV) in the environment and have important implications for the remediation of uranium contamination.
Subject(s)
Ferric Compounds , Uranium , Clay , Ligands , Edetic Acid , Minerals , Oxidation-ReductionABSTRACT
Microplastic records from lake cores can reconstruct the plastic pollution history. However, the associations between anthropogenic activities and microplastic accumulation are not well understood. Huguangyan Maar Lake (HML) is a deep-enclosed lake without inlets and outlets, where the sedimentary environment is ideal for preserving a stable and historical microplastic record. Microplastic (size: 10-500 µm) characteristics in the HML core were identified using the Laser Direct Infrared Imaging system. The earliest detectable microplastics appeared unit in 1955 (1.1 items g-1). The microplastic abundance ranged from n.d. to 615.2 items g-1 in 1955-2019 with an average of 134.9 items g-1. The abundance declined slightly during the 1970s and then increased rapidly after China's Reform and Opening Up in 1978. Sixteen polymer types were detectable, with polyethylene and polypropylene dominating, accounting for 23.5 and 23.3% of the total abundance, and the size at 10-100 µm accounted for 80%. Socioeconomic factors dominated the microplastic accumulation based on the random forest modeling, and the contributions of GDP per capita, plastic-related industry yield, and total crop yield were, respectively, 13.9, 35.1, and 9.3% between 1955-2019. The total crop yield contribution further increased by 1.7% after 1978. Coarse sediment particles increased with soil erosion exacerbated microplastics discharging into the sediment.
Subject(s)
Environmental Monitoring , Lakes , Microplastics , China , Microplastics/analysis , Water Pollutants, Chemical/analysis , Plastics , Geologic Sediments/chemistryABSTRACT
PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model. RESULTS: A one-compartment model with first-order absorption was employed to fit the base model. A total of 74 pediatric patients and 600 observations of whole blood concentration were included. The final model included weight (WT) in clearance (CL), alongside post-operative day (POD), fluconazole (FLUC), voriconazole (VORI), posaconazole (POSA), and red blood cell count (RBC) significantly. All the model evaluations were passed. CONCLUSION: In the PPK model based on the pediatric cohort on CsA with thalassemia undergoing allogeneic HSCT, WT, POD, FLUC, VORI, POSA, and RBC were found to be the significant factors influencing CL of CsA. The reliability and robustness of the final model were excellent. It is expected that the PPK model can assist in individualizing dosing strategy clinically.
Subject(s)
Hematopoietic Stem Cell Transplantation , Thalassemia , Humans , Child , Cyclosporine/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Retrospective Studies , Reproducibility of Results , Models, Biological , Voriconazole , Fluconazole , Thalassemia/surgeryABSTRACT
We propose a model-driven projected algebraic reconstruction technique (PART)-network (PART-Net) that leverages the advantages of the traditional model-based method and the neural network to improve the imaging quality of diffuse fluorescence tomography. In this algorithm, nonnegative prior information is incorporated into the ART iteration process to better guide the optimization process, and thereby improve imaging quality. On this basis, PART in conjunction with a residual convolutional neural network is further proposed to obtain high-fidelity image reconstruction. The numerical simulation results demonstrate that the PART-Net algorithm effectively improves noise robustness and reconstruction accuracy by at least 1-2 times and exhibits superiority in spatial resolution and quantification, especially for a small-sized target (r=2m m), compared with the traditional ART algorithm. Furthermore, the phantom and in vivo experiments verify the effectiveness of the PART-Net, suggesting strong generalization capability and a great potential for practical applications.
ABSTRACT
INTRODUCTION AND HYPOTHESIS: The objective was to investigate the correlation between endogenous vaginal microecological alterations and female pelvic organ prolapse (POP). METHODS: Patients who underwent vaginal hysterectomy were retrospectively analyzed as the POP group (n = 30) and the non-POP group (n = 30). The vaginal microbial metabolites and enzyme levels were tested using the dry chemoenzymatic method. The mRNA and protein expression were tested using real-time quantitative PCR and immunohistochemistry. SPSS version 25.0 and GraphPad Prism 8.0 were performed for statistical analysis. RESULTS: Compared with the non-POP group, the vaginal pH, H2O2 positivity and leukocyte esterase positivity were higher in patients with POP (all p < 0.05). Further analysis showed that patients with pelvic organ prolapse quantification (POP-Q) stage IV had higher rates of vaginal pH, H2O2 positivity and leukocyte esterase positivity than those with POP-Q stage III. Additionally, the mRNA expression of decorin (DCN), transforming growth factor beta 1 (TGF-ß1), and matrix metalloproteinase-3 (MMP-3) in uterosacral ligament tissues were higher, whereas collagen I and III were lower. Similarly, the positive expression of MMP-3 in uterosacral ligament tissue was significantly upregulated in the POP group compared with the non-POP group (p = 0.035), whereas collagen I (p = 0.004) and collagen III (p = 0.019) in uterosacral ligament tissue were significantly downregulated in the POP group. Correlation analysis revealed that there was a significant correlation between vaginal microecology and collagen metabolism. In addition, MMP-3 correlated negatively with collagen I and collagen III (p = 0.002, r = -0.533; p = 0.002, r = -0.534 respectively), whereas collagen I correlated positively with collagen III (p = 0.001, r = 0.578). CONCLUSIONS: Vaginal microecological dysbiosis affects the occurrence of female POP, which could be considered a novel therapeutic option.
Subject(s)
Pelvic Organ Prolapse , Vagina , Female , Humans , Pelvic Organ Prolapse/metabolism , Middle Aged , Retrospective Studies , Matrix Metalloproteinase 3/metabolism , Decorin/metabolism , Decorin/genetics , Aged , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Hydrogen Peroxide/metabolism , Hydrogen-Ion Concentration , Hysterectomy, Vaginal , Collagen Type I/metabolism , Collagen Type I/genetics , Collagen Type III/metabolism , Collagen Type III/genetics , RNA, Messenger/metabolism , Ligaments/metabolism , Microbiota , AdultABSTRACT
Wearable devices have been widely used for the home monitoring of physical activities and healthcare conditions, among which ambulatory electrocardiogram (ECG) stands out for the diagnostic cardiovascular information it contains. Continuous and unobtrusive sensing often requires the integration of wearable sensors to existing devices such as watches, armband, headphones, etc.; nonetheless, it is difficult to detect high-quality ECG due to the nature of low signal amplitude at these areas. In this paper, a high-performance system with multi-channel signal superposition for weak ECG real-time detection is proposed. Firstly, theoretical analysis and simulation is performed to demonstrate the effectiveness of this system design. The detection system, including electrode array, acquisition board, and the application (APP), is then developed and the electrical characteristics are measured. A common mode rejection ratio (CMRR) of up to 100 dB and input inferred voltage noise below 1 µV are realized. Finally, the technique is implemented in form of ear-worn and armband devices, achieving an SNR over 20 dB. Results are also compared with the simultaneous recording of standard lead I ECG. The correlation between the heart rates derived from experimental and standard signals is higher than 0.99, showing the feasibility of the proposed technique.
Subject(s)
Signal Processing, Computer-Assisted , Wearable Electronic Devices , Electrocardiography, Ambulatory , Electrocardiography , HeartABSTRACT
AIM: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and intracranial plaque features, as well as the risk factors related to the severity and recurrence of cerebral ischemic events. METHODS: We enrolled 170 patients with cerebral ischemic events. Baseline demographic characteristics and laboratory indicators were collected from all participants. All patients were assessed by high-resolution magnetic resonance vessel wall imaging for culprit plaque characteristics and intracranial atherosclerotic burden. Outpatient or telephone follow-up were conducted at 1, 3, and 6 months after discharge. RESULTS: SIRI levels were significantly associated with the enhanced plaque number (r = 0.205, p = 0.007), total plaque stenosis score (r = 0.178, p = 0.020), total plaque enhancement score (r = 0.222, p = 0.004), intraplaque hemorrhage (F = 5.630, p = 0.004), and plaque surface irregularity (F = 3.986, p = 0.021). Higher SIRI levels (OR = 1.892), total plaque enhancement score (OR = 1.392), intraplaque hemorrhage (OR = 3.370) and plaque surface irregularity (OR = 2.846) were independent risk factors for moderate-severe stroke, and these variables were significantly positively correlated with NIHSS (P < 0.05 for all). In addition, higher age (HR = 1.063, P = 0.015), higher SIRI levels (HR = 2.003, P < 0.001), and intraplaque hemorrhage (HR = 4.482, P = 0.008) were independently associated with recurrent stroke. CONCLUSIONS: Higher SIRI levels may have adverse effects on the vulnerability and burden of intracranial plaques, and links to the severity and recurrence of ischemic events. Therefore, SIRI may provide important supplementary information for evaluating intracranial plaque stability and risk stratification of patients.
Subject(s)
Intracranial Arteriosclerosis , Plaque, Atherosclerotic , Stroke , Humans , Magnetic Resonance Angiography/methods , Stroke/etiology , Magnetic Resonance Imaging/adverse effects , Plaque, Atherosclerotic/complications , Hemorrhage/complications , Systemic Inflammatory Response Syndrome/complications , Intracranial Arteriosclerosis/complications , Intracranial Arteriosclerosis/diagnostic imaging , Intracranial Arteriosclerosis/pathologyABSTRACT
OBJECTIVE: self-care is critically important for the long-term management of heart failure (HF) patients, with caregivers playing an important role in promoting self-care. However, adherence to self-care is typically low among HF patients worldwide. METHODS: In-depth qualitative interviews were conducted with individuals diagnosed with HF. To structure the interview guide and underpin the analysis, two established behavioral science frameworks, the Behavior Change Wheel (BCW) and the Theoretical Domains Framework (TDF), were used in this study. RESULTS: A total of 32 participants were included (n = 16 patients, n = 16 caregivers), with themes involving: barriers included: "Self-care with Limited Capability," "Insufficient External Support," "Lack of Motivation for Self-Care." Facilitators included: "Striving to Adapt to Disease Demands," "Adequate External Support," "Positive Health Behaviors and Experiences." CONCLUSIONS: Providing positive support to heart failure patients and their caregivers, along with cultivating intrinsic motivation for behavioral change, can enhance self-care ability.