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Background: Essential trace elements are vital for human growth and development. Nevertheless, excessive intake can pose risks. As of yet, no research has looked at the possibility of a relationship between the prevalence of gallstones and urinary concentrations of nickel, molybdenum, and iodine. Objectives: The purpose of this study was to examine the correlation between urinary levels of iodine, molybdenum, and nickel and the occurrence of gallstones in a U.S. population and to verify whether excessive iodine intake is associated with the occurrence of gallstones. Methods: Data from 2,734 participants that were gathered between 2017 and 2020 were examined. Employing inductively coupled plasma mass spectrometry (ICP-MS), the levels of nickel (Ni), iodine (I), and molybdenum (Mo) in the urine were determined. Gallstones presence was determined using a standardized questionnaire. Restricted cubic spline analysis, subgroup analysis, and logistic regression analysis were used to evaluate the relationship between the occurrence of gallstones and urinary essential trace elements. Results: The logistic regression analysis indicated an increased risk of gallstone development in Quartiles 2, Quartiles 3, and Quartiles 4 groups in comparison to the Quartiles 1 group, based on urinary iodine levels (OR = 1.69, 95% CI: 1.11-2.56; OR = 1.68, 95% CI: 1.10-2.55; OR = 1.65, 95% CI: 1.09-2.51). Urinary iodine levels were nonlinearly positively linked with the development of gallstones, according to restricted cubic spline analysis (P-Nonlinear = 0.032). Subgroup analyses showed that high levels of urinary iodine were associated with a high risk of gallstones in different populations, and were more pronounced in adults aged 60 years and older, in women, with a BMI ≥ 25, and in diabetic patients. Conclusion: Our research revealed a correlation between an increased risk of gallstones and increasing urinary iodine levels. Urinary iodine levels serve as indicators of the body's iodine status, thus suggesting that excessive iodine intake may be linked to an elevated risk of gallstone formation.
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Graphene has tremendous potential in future electronics due to its superior force, electrical, and thermal properties. However, the development of graphene devices is limited by its complex, high-cost, and low-efficiency preparation process. This study proposes a novel laser bidirectional graphene printing (LBGP) process for the large-scale preparation of patterned graphene films. In LBGP, a sandwich sample composed of a thermoplastic elastomer (TPE) substrate, carbon precursor powder, and a glass cover is irradiated by a nanosecond pulsed laser. The laser photothermal effect converts the carbon precursor into graphene, with partial graphene sheets deposited directly on the TPE substrate and the remaining transferred to the glass cover via a laser-induced plasma plume. This method simultaneously prepares two face-to-face graphene films in a single laser irradiation, integrating synthesis, transfer, and patterning. The resulting graphene patterns demonstrate good performance in flexible pressure sensing and Joule heating, showcasing high sensitivity (7.7 kPa-1), fast response (37 ms), and good cycling stability (2000 cycles) for sensors, and high heating rate (1 °C s-1) and long-term stability (3000 s) for heaters. It is believed that the simple, low-cost, and efficient LBGP process can promote the development of graphene electronics and laser manufacturing processes.
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Flexible sensors have developed rapidly due to their great application potential in the intelligent era. However, the frequent bending work requirements pose a serious challenge to the mechanical reliability of flexible sensors. Herein, a strategy of using a new multielectrode layout to achieve multiple sensing signals based on one external signal is proposed for the first time to improve the reliability of flexible piezoresistive sensors. The multielectrode layout consists of a pair of interdigital electrodes and a bottom electrode. The interdigitated electrodes are used to sense the change in the surface resistance of the sensor, and the interdigital electrodes and the bottom electrode are used to sense the change in the bulk resistance of the sensor. As a result, without increasing the sensing unit area, the electrode layout allows the sensor to generate three response electrical signals when sensing an external pressure, thus improving the reliability of the sensor. Based on the electrode layout, a highly reliable flexible piezoresistive sensor with a multilevel porous structure is obtained by a microwave foaming method with a template. In the working state of sensing surface resistance, the sensor has a 22.12 kPa-1 sensitivity. Meanwhile, in the working state of sensing bulk resistance, the sensor shows a 55.17 kPa-1 sensitivity. Furthermore, the sensor is applied to monitor human pulse and speech signals, demonstrating its multisignal output characteristics and potential applications in flexible electronics. In conclusion, the new strategy of using the proposed electrode layout to improve the reliability of flexible sensors is expected to greatly promote the practical application of flexible electronics.
Subject(s)
Electrodes , Humans , Wearable Electronic Devices , Pulse , Equipment DesignABSTRACT
Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.
Subject(s)
Epithelial-Mesenchymal Transition , Matrix Metalloproteinase 9 , Neoplasm Metastasis , Receptors, G-Protein-Coupled , Sweetening Agents , Humans , Epithelial-Mesenchymal Transition/drug effects , Receptors, G-Protein-Coupled/metabolism , Sweetening Agents/pharmacology , Cell Line, Tumor , Matrix Metalloproteinase 9/metabolism , Glycosylation/drug effects , Signal Transduction/drug effects , Phenotype , Animals , Taste/drug effects , Cell Movement/drug effects , NeuraminidaseABSTRACT
Daqu is a saccharification agent required for fermenting Baijiu, a popular Chinese liquor. Our objective was to investigate the relationships between physicochemical indices, microbial community diversity, and metabolite profiles of strong-flavor Jinhui Daqu during different storage periods. During different storage periods of Jinhui Daqu, we combined Illumina MiSeq sequencing and non-target sequencing techniques to analyze dynamic changes of the microbial community and metabolite composition, established a symbiotic network and explored the correlation between dominant microorganisms and differential metabolites in Daqu. Fungal community diversity in 8d_Daqu was higher than that in 45d_Daqu and 90d_Daqu, whereas bacterial community diversity was higher in 90d_Daqu. Twelve bacterial and four fungal genera were dominant during storage of Daqu. Bacillus, Leuconostoc, Kroppenstedtia, Lactococcus, Thermomyces and Wickerhamomyces decreased as the storage period increased. Differences of microbiota structure led to various metabolic pathways, and 993 differential metabolites were found in all Daqu samples. Differential microorganisms were significantly related to key metabolites. Major metabolic pathways involved in the formation of amino acids and lipids, such as l-arogenate and hydroxyproline, were identified. Interactions between moisture, acidity, and microbes may drive the succession of the microbial community, which further affects the formation of metabolites.
Subject(s)
Bacillus , Microbiota , Fermentation , Bacteria , MetabolomeABSTRACT
BACKGROUND: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. METHODS: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. RESULTS: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. CONCLUSIONS: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.
Subject(s)
Alzheimer Disease , Inflammasomes , Humans , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , tau Proteins/genetics , tau Proteins/metabolism , HEK293 Cells , Molecular Docking Simulation , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Mice, Transgenic , AcetyltransferasesABSTRACT
BACKGROUND: Dyslipidemia and abnormalities in cholesterol metabolism are commonly observed in individuals with gallstone disease. Previous research has demonstrated that dietary magnesium can influence lipid metabolism. The atherogenic index of plasma (AIP) has emerged as a novel lipid marker. This study aimed to examine the possible correlation between dietary magnesium intake and gallstones and the potential mediating role of AIP in US adults. METHODS: A total of 4,841 adults were included in this study from the National Health and Nutrition Examination Survey (NHANES) conducted from 2017 to 2020. A variety of statistical techniques such as logistic regression, subgroup analysis, smoothed curve fitting, and causal mediation analysis were utilized to analyze the information collected from the participants. RESULTS: In the fully adjusted model, a statistically noteworthy inverse relationship was observed between dietary magnesium intake and the presence of gallstones, as indicated by an odds ratio (OR) of 0.58 and a 95% confidence interval (CI) of (0.42, 0.81). Causal intermediary analysis revealed that the association between magnesium intake and gallstones was partially mediated by AIP, with a mediation ratio of 3.2%. CONCLUSION: According to this study, dietary magnesium intake had a significant linear negative association with the prevalence of gallstones, in which AIP played a mediating role. This discovery offers novel perspectives on the prevention and management of gallstones.
Subject(s)
Atherosclerosis , Gallstones , Adult , Humans , Gallstones/epidemiology , Nutrition Surveys , Magnesium , Atherosclerosis/epidemiologyABSTRACT
The success of existing cross-modal retrieval (CMR) methods heavily rely on the assumption that the annotated cross-modal correspondence is faultless. In practice, however, the correspondence of some pairs would be inevitably contaminated during data collection or annotation, thus leading to the so-called Noisy Correspondence (NC) problem. To alleviate the influence of NC, we propose a novel method termed Consistency REfining And Mining (CREAM) by revealing and exploiting the difference between correspondence and consistency. Specifically, the correspondence and the consistency only be coincident for true positive and true negative pairs, while being distinct for false positive and false negative pairs. Based on the observation, CREAM employs a collaborative learning paradigm to detect and rectify the correspondence of positives, and a negative mining approach to explore and utilize the consistency. Thanks to the consistency refining and mining strategy of CREAM, the overfitting on the false positives could be prevented and the consistency rooted in the false negatives could be exploited, thus leading to a robust CMR method. Extensive experiments verify the effectiveness of our method on three image-text benchmarks including Flickr30K, MS-COCO, and Conceptual Captions. Furthermore, we adopt our method into the graph matching task and the results demonstrate the robustness of our method against fine-grained NC problem. The code is available on https://github.com/XLearning-SCU/2024-TIP-CREAM.
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Myocardial ischemia/reperfusion (MI/R) injury is a major cause of adverse outcomes of revascularization following myocardial infarction. Anaerobic glycolysis during myocardial ischemia is well studied, but the role of aerobic glycolysis during the early phase of reperfusion is incompletely understood. Lactylation of Histone H3 (H3) is an epigenetic indicator of the glycolytic switch. Heat shock protein A12A (HSPA12A) is an atypic member of the HSP70 family. In the present study, we report that, during reperfusion following myocardial ischemia, HSPA12A was downregulated and aerobic glycolytic flux was decreased in cardiomyocytes. Notably, HSPA12A KO in mice exacerbated MI/R-induced aerobic glycolysis decrease, cardiomyocyte death, and cardiac dysfunction. Gain- and loss-of-function studies demonstrated that HSPA12A was required to support cardiomyocyte survival upon hypoxia/reoxygenation (H/R) challenge and that its protective effects were mediated by maintaining aerobic glycolytic homeostasis for H3 lactylation. Further analyses revealed that HSPA12A increased Smurf1-mediated Hif1α protein stability, thus increasing glycolytic gene expression to maintain appropriate aerobic glycolytic activity to sustain H3 lactylation during reperfusion and, ultimately, improving cardiomyocyte survival to attenuate MI/R injury.
Subject(s)
Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Animals , Mice , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Myocardial Infarction/metabolism , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Myocytes, Cardiac/metabolismABSTRACT
Background: With the use of cobalt alloys in medical prosthetics, the risk of cobalt exposure has increased. The objective of this study was to investigate the correlation between blood cobalt levels and the occurrence of gallstones utilizing data from the National Health and Nutrition Examination Survey (NHANES). Methods: Data collected between 2017 and 2020 were analyzed, encompassing a total of 5,610 participants. Cobalt concentrations in whole blood specimens were directly measured using inductively coupled plasma mass spectrometry (ICP-MS). The presence of gallstones was ascertained through a standardized questionnaire. To assess the association between blood cobalt levels and the presence of gallstones, logistic regression analysis, restricted cubic spline analysis, and subgroup analysis were utilized. Results: The results of logistic regression analysis revealed a heightened risk of developing gallstones in the Quartiles 2 and Quartiles 4 groups based on blood cobalt levels when compared to the Quartiles 1 group (OR = 1.54, 95% CI: 1.15-2.07; OR = 1.35, 95% CI: 1.03-1.77). The restricted cubic spline analysis exhibited a positive linear correlation between blood cobalt levels and the occurrence of gallstones. Subgroup analyses further demonstrated a statistically significant correlation between the Quartiles 4 category of blood cobalt levels and an elevated risk of gallstones, particularly among individuals aged 60 years or older, females, those with a body mass index (BMI) equal to or exceeding 25, serum total cholesterol levels below 200 mg/dL, as well as individuals diagnosed with hypertension or diabetes. Conclusion: Our study findings indicate a notable association between elevated blood cobalt levels and an increased risk of gallstones. To establish a causal relationship between blood cobalt levels and the elevated risk of developing gallstones, further prospective cohort studies are warranted.
Subject(s)
Gallstones , Female , Humans , Gallstones/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Body Mass Index , Cobalt/adverse effectsABSTRACT
Apple rust, caused by Gymnosporangium yamadae, poses a significant challenge to apple production. Prior studies have underscored the pivotal role played by endophytic microbial communities, intimately linked with the host, in influencing plant diseases and their pathogenic outcomes. The objective of this study is to scrutinize alternations in endophytic microbial communities within apple leaves at different stages of apple rust using high-throughput sequencing technology. The findings revealed a discernible pattern characterized by an initial increase and subsequent decrease in the alpha diversity of microbial communities in diseased leaves. A microbial co-occurrence network analysis revealed that the complexity of the bacterial community in diseased leaves diminished initially and then rebounded during the progression of the disease. Additionally, employing the PICRUSt2 platform, this study provided preliminary insights into the functions of microbial communities at specific disease timepoints. During the spermogonial stage, endophytic bacteria particularly exhibited heightened activity in genetic information processing, metabolism, and environmental information processing pathways. Endophytic fungi also significantly enriched a large number of metabolic pathways during the spermogonial stage and aecial stage, exhibiting abnormally active life activities. These findings establish a foundation for comprehending the role of host endophytes in the interaction between pathogens and hosts. Furthermore, they offer valuable insights for the development and exploitation of plant endophytic resources, thereby contributing to enhanced strategies for managing apple rust.
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Skin-like flexible pressure sensors with good sensing performance have great application potential, but their development is limited owing to the need for multistep, high-cost, and low-efficiency preparation processes. Herein, a simple, low-cost, and efficient laser-induced forming process is proposed for the first time to prepare a skin-like flexible piezoresistive sensor. In the laser-induced forming process, based on the photothermal effect of graphene and the foaming effect of glucose, a skin-like polydimethylsiloxanes (PDMS) film with porous structures and surface protrusions is obtained by using infrared laser irradiation of the glucose/graphene/PDMS prepolymer film. Further, based on the skin-like PDMS film with a graphene conductive layer, a new skin-like flexible piezoresistive sensor is obtained. Due to the stress concentration caused by the surface protrusions and the low stiffness caused by the porous structures, the flexible piezoresistive sensor realizes an ultrahigh sensitivity of 1348 kPa-1 at 0-2 kPa, a wide range of 200 kPa, a fast response/recovery time of 52 ms/35 ms, and good stability over 5000 cycles. The application of the sensor to the detection of human pulses and robot clamping force indicates its potential for health monitoring and soft robots. Furthermore, in combination with the neural network (CNN) algorithm in artificial intelligence technology, the sensor achieves 95% accuracy in speech recognition, which demonstrates its great potential for intelligent wearable electronics. Especially, the laser-induced forming process is expected to facilitate the efficient, large-scale preparation of flexible devices with multilevel structures.
Subject(s)
Graphite , Speech Perception , Humans , Artificial Intelligence , Infrared Rays , Dimethylpolysiloxanes , GlucoseABSTRACT
The development of high-performance flexible pressure sensors with porous hierarchical microstructures is limited by the complex and time-consuming preparation processes of porous hierarchical microstructures. In this study, a simple modified heat curing process was first proposed to achieve one-step preparation of porous hemispherical microstructures on a polydimethylsiloxane (PDMS) substrate. In this process, a laser-prepared template was used to form surface microstructures on PDMS film. Meanwhile, the thermal decomposition of glucose monohydrate additive during heat curing of PDMS led to the formation of porous structures within PDMS film. Further, based on the obtained PDMS/CNTs electrodes with porous hemisphere array and ionic polymer dielectric layers, high-performance ionic piezocapacitive sensors were realized. Under the synergistic effect of the low-stiffness porous hemisphere microstructure and the electric double layer of the ionic polymer film, the sensor based on an ionic polymer film with a 1:0.75 ratio of P(VDF-HFP):[EMIM][TFSI] not only achieves a sensitivity of up to 106.27 kPa-1 below 3 kPa, but also has a wide measurement range of over 400 kPa, which has obvious advantages in existing flexible piezocapacitive sensors. The rapid response time of 110 s and the good stability of 2300 cycles of the sensor further elucidate its practicality. The application of the sensor in pulse monitoring, speech recognition, and detection of multiple dynamic loads verifies its excellent sensing performance. In short, the proposed heat curing process can simultaneously form porous structures and surface microstructures on PDMS films, greatly simplifying the preparation process of porous hierarchical microstructures and providing a simple and feasible way to obtain high-performance flexible pressure sensors.
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BACKGROUND: Artificial intelligence (AI) applied to 12-lead electrocardiographs (ECGs) can detect hypertrophic cardiomyopathy (HCM). OBJECTIVES: The purpose of this study was to determine if AI-enhanced ECG (AI-ECG) can track longitudinal therapeutic response and changes in cardiac structure, function, or hemodynamics in obstructive HCM during mavacamten treatment. METHODS: We applied 2 independently developed AI-ECG algorithms (University of California-San Francisco and Mayo Clinic) to serial ECGs (n = 216) from the phase 2 PIONEER-OLE trial of mavacamten for symptomatic obstructive HCM (n = 13 patients, mean age 57.8 years, 69.2% male). Control ECGs from 2,600 age- and sex-matched individuals without HCM were obtained. AI-ECG output was correlated longitudinally to echocardiographic and laboratory metrics of mavacamten treatment response. RESULTS: In the validation cohorts, both algorithms exhibited similar performance for HCM diagnosis, and exhibited mean HCM score decreases during mavacamten treatment: patient-level score reduction ranged from approximately 0.80 to 0.45 for Mayo and 0.70 to 0.35 for USCF algorithms; 11 of 13 patients demonstrated absolute score reduction from start to end of follow-up for both algorithms. HCM scores were significantly associated with other HCM-relevant parameters, including left ventricular outflow tract gradient at rest, postexercise, and with Valsalva, and NT-proBNP level, independent of age and sex (all P < 0.01). For both algorithms, the strongest longitudinal correlation was between AI-ECG HCM score and left ventricular outflow tract gradient postexercise (slope estimate: University of California-San Francisco 0.70 [95% CI: 0.45-0.96], P < 0.0001; Mayo 0.40 [95% CI: 0.11-0.68], P = 0.007). CONCLUSIONS: AI-ECG analysis longitudinally correlated with changes in echocardiographic and laboratory markers during mavacamten treatment in obstructive HCM. These results provide early evidence for a potential paradigm for monitoring HCM therapeutic response.
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Neonatal maternal separation (NMS) is an early-life stress (ELS) that can result in adult visceral hypersensitivity, which is usually manifested as chronic visceral pain. Although mast cells and corticotropin-releasing hormone (CRH) neurons are involved in stress response, whether there is an interaction between mast cells and CRH neurons in hypothalamic paraventricular nucleus (PVN) during the ELS-induced visceral hypersensitivity remains elusive. Herein, we established an NMS model by separating neonatal mice from their mothers, and observed that these mice presented visceral hypersensitivity in adulthood, as indicated by elevated abdominal withdrawal reflex and lowered visceral pain threshold. The NMS-induced adult visceral hypersensitivity was accompanied by activation of mast cells and CRH neurons in PVN. Also, NMS increased the histamine content (an inflammatory mediator mainly released by mast cells) and histamine H2 receptor (H2R) expression of CRH neurons in PVN. Remarkably, intra-PVN administration with mast cell stabilizer attenuated the NMS-induced CRH neuronal activation and adult visceral pain, while histamine administration showed the opposite effects. Moreover, intra-PVN injection with H2R antagonist alleviated the NMS-induced CRH neuronal activation, PKA and CREB phosphorylation, and importantly, adult visceral pain. Together, our findings revealed a role of an interaction between paraventricular mast cells and CRH neurons in NMS-induced adult visceral hypersensitivity, thereby providing a perspective for the management of visceral pain.
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Preparing hybrid microstructures on flexible substrates is a crucial approach to achieving highly sensitive flexible pressure sensors. However, the preparation of hybrid microstructures on soft materials often faces complex, time-consuming, and costly problems, which hampers the advancement of highly sensitive flexible sensors. Herein, based on a 3D-printing template and a household microwave oven, a simple, green, and one-step microwave irradiation process using glucose porogen is applied to develop a flexible pressure sensor with a volcano-sponge-like porous dome structure based on porous polydimethylsiloxane (PDMS). Due to the easily deformable porous dome on the porous PDMS substrate, the flexible pressure sensor showcases exceptional sensitivity of 611.85 kPa-1 in 0-1 and 50.31 kPa-1 over a wide range of 20-80 kPa. Additionally, the sensor takes only 43 ms to respond, 123 ms to recover, and presents excellent stability (>1100 cycles). In application testing, the sensor effectively captures pulse signals, speech signals, tactile signals from a mechanical gripper, and gesture signals, demonstrating its potential applications in medical diagnosis and robotics. In conclusion, the microwave irradiation method based on template and glucose porogen provides a new way for the simple, low-cost, and green preparation of porous-surface hybrid microstructures on polymers and high-performance flexible pressure sensors.
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Single-cell multi-omics data integration aims to reduce the omics difference while keeping the cell type difference. However, it is daunting to model and distinguish the two differences due to cell heterogeneity. Namely, even cells of the same omics and type would have various features, making the two differences less significant. In this work, we reveal that instead of being an interference, cell heterogeneity could be exploited to improve data integration. Specifically, we observe that the omics difference varies in cells, and cells with smaller omics differences are easier to be integrated. Hence, unlike most existing works that homogeneously treat and integrate all cells, we propose a multi-omics data integration method (dubbed scBridge) that integrates cells in a heterogeneous manner. In brief, scBridge iterates between i) identifying reliable scATAC-seq cells that have smaller omics differences, and ii) integrating reliable scATAC-seq cells with scRNA-seq data to narrow the omics gap, thus benefiting the integration for the rest cells. Extensive experiments on seven multi-omics datasets demonstrate the superiority of scBridge compared with six representative baselines.
Subject(s)
Chromatin Immunoprecipitation Sequencing , Single-Cell Gene Expression Analysis , Chromatin Immunoprecipitation Sequencing/methods , Single-Cell Analysis/methods , MultiomicsABSTRACT
Due to the advantages of high porosity, excellent conductivity, and tunable morphology, carbonized metal-organic framework (C-MOF) is expected to become an ideal material for constructing high-performance flexible pressure sensor. Herein, to achieving the suitable morphology of C-MOF for piezoresistive sensors, a rapid thermal process (RTP) was used for carbonization of NiCo-MOF, and the petal-shaped NiCo alloy nanoparticles/nanoporous carbon composites (NiCo-NPCs) were obtained. Compared with NiCo-NPCs carbonized by common thermal process (CTP), NiCo-NPCs carbonized by RTP exhibit a modified morphology with smaller particle size and larger most frequent pore diameter. Due to the modified morphology, the piezoresistive sensor with RTP-carbonized NiCo-NPCs has a high sensitivity of 62.13 kPa-1at 0-3 kPa, which is 3.46 times higher than that of the sensor with CTP-carbonized NiCo-NPCs. Meanwhile, the sensor shows an ultra-wide range of 1000 kPa, excellent cycle stability (>4000 cycles), and fast response/recovery time of 25/44 ms. Furthermore, the application of the sensor in dynamic loading test, airflow monitoring, voice recognition, and gesture detection demonstrates its great application prospects. In short, this work investigates the application of carbonized NiCo-MOFs in flexible pressure sensors, and provides a new strategy to improve the performance of piezoresistive sensors with porous carbon derived from MOFs.
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Microstructures can effectively improve the sensing performance of flexible piezocapacitive sensors. Simple, low-cost fabrication methods for microstructures are key to facilitating the practical application of piezocapacitive sensors. Herein, based on the laser thermal effect and the thermal decomposition of glucose, a rapid, simple, and low-cost laser direct-printing process is proposed for the preparation of a polydimethylsiloxane (PDMS)-based electrode with a hybrid microstructure. Combining the PDMS-based electrode with an ionic gel film, highly sensitive piezocapacitive sensors with different hybrid microstructures are realized. Due to the good mechanical properties brought about by the hybrid microstructure and the double electric layer induced by the ionic gel film, the sensor with a porous X-type microstructure exhibits an ultrahigh sensitivity of 92.87 kPa-1 in the pressure range of 0-1000 Pa, a wide measurement range of 100 kPa, excellent stability (>3000 cycles), fast response time (100 ms) and recovery time (101 ms), and good reversibility. Furthermore, the sensor is used to monitor human physiological signals such as throat vibration, pulse, and facial muscle movement, demonstrating the application potential of the sensor in human health monitoring. Most importantly, the laser direct-printing process provides a new strategy for the one-step preparation of hybrid microstructures on thermal curing polymers.
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BACKGROUND: Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery. MATERIALS AND METHODS: Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size. RESULTS: Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17-15.18, P =0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups. CONCLUSIONS: Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.