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1.
Microsyst Nanoeng ; 10: 102, 2024.
Article in English | MEDLINE | ID: mdl-39045232

ABSTRACT

With the rapid development of various fields, including aerospace, industrial measurement and control, and medical monitoring, the need to quantify flow velocity measurements is increasing. It is difficult for traditional flow velocity sensors to fulfill accuracy requirements for velocity measurements due to their small ranges, susceptibility to environmental impacts, and instability. Herein, to optimize sensor performance, a flexible microelectromechanical system (MEMS) thermal flow sensor is proposed that combines the working principles of thermal loss and thermal temperature difference and utilizes a flexible cavity substrate made of a low-thermal-conductivity polyimide/SiO2 (PI/SiO2) composite porous film to broaden the measurement range and improve the sensitivity. The measurement results show that the maximum measurable flow velocity can reach 30 m/s with a resolution of 5.4 mm/s. The average sensitivities of the sensor are 59.49 mV/(m s-1) in the medium-to-low wind velocity range of 0-2 m/s and 467.31 mV/(m s-1) in the wind velocity range of 2-30 m/s. The sensor proposed in this work can enable new applications of flexible flow sensors and wearable devices.

2.
BMC Geriatr ; 24(1): 622, 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39034410

ABSTRACT

PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.


Subject(s)
Cardiovascular Diseases , Sleep Initiation and Maintenance Disorders , Humans , Male , Female , Aged , Prospective Studies , Cardiovascular Diseases/mortality , Cardiovascular Diseases/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/mortality , Sleep Initiation and Maintenance Disorders/complications , Sleep Apnea, Obstructive/mortality , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Aged, 80 and over , Cause of Death/trends , Risk Factors
3.
Microsyst Nanoeng ; 10: 104, 2024.
Article in English | MEDLINE | ID: mdl-39050588

ABSTRACT

Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold-gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and -0.19% FS in the range of 0-20 MPa and -40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

4.
J Extracell Vesicles ; 13(7): e12483, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39051765

ABSTRACT

Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.


Subject(s)
Extracellular Vesicles , Extracellular Vesicles/metabolism , Animals , Humans , Mice , Dehydration/metabolism , Cancer Vaccines
5.
Rapid Commun Mass Spectrom ; 38(18): e9865, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38982886

ABSTRACT

RATIONALE: The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues. METHODS: This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD). RESULTS: Chromatography was performed using a Shim-pack GISS-HP C18 metal-free column (3 µm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3-100 µg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%-89.72% and 41.98%-67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level. CONCLUSION: This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method.


Subject(s)
Drug Monitoring , Infliximab , Tandem Mass Spectrometry , Infliximab/blood , Humans , Drug Monitoring/methods , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Child , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/blood , Reproducibility of Results , Limit of Detection , Adolescent , Linear Models , Male
6.
Front Neurol ; 15: 1414959, 2024.
Article in English | MEDLINE | ID: mdl-38872825

ABSTRACT

Purpose: Identifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism. Method: Patients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated. Results: A total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p < 0.001). Interobserver agreement for identifying PPS was excellent (κ = 0.944). The sensitivity, specificity, PPV, NPV, and accuracy of the PPS for predicting ICAS were 52.6, 93.8, 83.3, 76.9, and 78.4%, respectively. Conclusion: The PPS on RAPID software is an imaging marker with high specificity for ICAS. Larger sample sizes are imperative to validate the findings.

7.
Opt Express ; 32(11): 19779-19791, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859104

ABSTRACT

Derived from infrared pyroelectric detection, typical terahertz (THz) pyroelectric detectors have low sensitivity at low-frequency THz bands. Based on the high-efficiency absorption of the metamaterial perfect absorber (MPA), a novel split ring hole metamaterial-enhanced pyroelectric detector is proposed to achieve efficient multi-narrowband THz detection. Using high frequency simulation software (HFSS), the dimensional parameters including ring radius, ring width, connection beam width, array period, and thickness, are optimized to enhance efficient multi-narrowband absorption. The as-optimized metamaterial-enhanced detectors are fabricated via micro-nano manufacturing technology. The voltage responsiveness and noise equivalent power of the metamaterial-enhanced detector are tested by THz focused optical path and compared with those of the typical pyroelectric detector and the simulated MPA absorptivity. The results indicate that the metamaterial-enhanced detector has a multi-narrowband detection capability at 0.245 THz, 0.295 THz, and 0.38 THz, which is close to the simulated MPA absorptivity. Compared to the typical pyroelectric detector, the split ring hole metamaterial-enhanced detector can simultaneously achieve thermal absorption, thermal conduction, and pyroelectricity in the same MPA structure, providing faster response speed above 100 Hz chopper frequency and two times higher detection sensitivity at multi-narrowband THz frequencies. This research can be used for THz sensing, absorption filtering, biological macromolecule detection, and other applications.

8.
Biomed Pharmacother ; 177: 116975, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38925017

ABSTRACT

The interaction between the gut microbiota and mercaptopurine (6-MP), a crucial drug used in pediatric acute lymphoblastic leukemia (ALL) treatment, has not been extensively studied. Here we reveal the significant perturbation of gut microbiota after 2-week 6-MP treatment in beagles and mice followed by the functional prediction that showed impairment of SCFAs production and altered amino acid synthesis. And the targeted metabolomics in plasma also showed changes in amino acids. Additionally, targeted metabolomics analysis of feces showed changes in amino acids and SCFAs. Furthermore, ablating the intestinal microbiota by broad-spectrum antibiotics exacerbated the imbalance of amino acids, particularly leading to a significant decrease in the concentration of S-adenosylmethionine (SAM). Importantly, the depletion of gut microbiota worsened the damage of small intestine caused by 6-MP, resulting in increased intestinal permeability. Considering the relationship between toxicity and 6-MP metabolites, we conducted a pharmacokinetic study in pseudo germ-free rats to confirm that gut microbiota depletion altered the methylation metabolites of 6-MP. Specifically, the concentration of MeTINs, a secondary methylation metabolite, showed a negative correlation with SAM, the pivotal methyl donor. Additionally, we observed a strong correlation between Alistipes and SAM levels in both feces and plasma. In conclusion, our study demonstrates that 6-MP disrupts the gut microbiota, and depleting the gut microbiota exacerbates 6-MP-induced intestinal toxicity. Moreover, SAM derived from microbiota plays a crucial role in influencing plasma SAM and the methylation of 6-MP. These findings underscore the importance of comprehending the role of the gut microbiota in 6-MP metabolism and toxicity.

9.
Front Pharmacol ; 15: 1399963, 2024.
Article in English | MEDLINE | ID: mdl-38903997

ABSTRACT

Background: Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC. Methods: Three mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs. Results: The analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time-response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects. Conclusion: This study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.

10.
Int J Antimicrob Agents ; 64(2): 107199, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38795931

ABSTRACT

OBJECTIVES: To establish a population pharmacokinetics (PopPK) model of nirmatrelvir in Chinese COVID-19 patients and provide reference for refining the dosing strategy of nirmatrelvir in patients confirmed to be infected with SARS-CoV-2. METHODS: A total of 80 blood samples were obtained from 35 mild to moderate COVID-19 patients who were orally administered nirmatrelvir/ritonavir tablets. The PopPK model of nirmatrelvir was developed using a nonlinear mixed effects modelling approach. The stability and prediction of the final model were assessed through a combination of goodness-of-fit and bootstrap method. The exposure of nirmatrelvir across various clinical scenarios was simulated using Monte Carlo simulations. RESULTS: The pharmacokinetics of nirmatrelvir was well characterised by a one-compartment model with first-order absorption, and with creatinine clearance (Ccr) as the significant covariate. Typical population parameter estimates of apparent clearance and distribution volume for a patient with a Ccr of 95.5 mL·min-1were 3.45 L·h-1 and 48.71 L, respectively. The bootstrap and visual predictive check procedures demonstrated satisfactory predictive performance and robustness of the final model. CONCLUSION: The final model was capable of offering an early prediction of drug concentration ranges for different nirmatrelvir dosing regimens and optimise the dose regimen of nirmatrelvir in individuals with confirmed SARS-CoV-2 infection.

11.
Biosens Bioelectron ; 258: 116291, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38735080

ABSTRACT

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.


Subject(s)
Biomarkers , Biosensing Techniques , Depressive Disorder, Major , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Humans , Biomarkers/analysis , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Point-of-Care Systems , Electrochemical Techniques/methods
13.
Biosens Bioelectron ; 255: 116090, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38569250

ABSTRACT

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.


Subject(s)
Biosensing Techniques , Heart Failure , Humans , Biomarkers , Prognosis , Natriuretic Peptide, Brain , Heart Failure/diagnosis , C-Reactive Protein/metabolism , Peptide Fragments
14.
Int Immunopharmacol ; 131: 111888, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38522139

ABSTRACT

OBJECTIVES: Osteoarthritis (OA) is a whole-joint disease in which the role of the infrapatellar fat pad (IFP) in its pathogenesis is unclear. Our study explored the cellular heterogeneity of IFP to understand OA and identify therapeutic targets. METHODS: Single-cell and single-nuclei RNA sequencing were used to analyze 10 IFP samples, comprising 5 from OA patients and 5 from healthy controls. Analyses included differential gene expression, enrichment, pseudotime trajectory, and cellular communication, along with comparative studies with visceral and subcutaneous fats. Key subcluster and pathways were validated using multiplex immunohistochemistry. RESULTS: The scRNA-seq performed on the IFPs of the OA and control group profiled the gene expressions of over 49,674 cells belonging to 11 major cell types. We discovered that adipose stem and progenitor cells (ASPCs), contributing to the formation of both adipocytes and synovial-lining fibroblasts (SLF). Interstitial inflammatory fibroblasts (iiFBs) were a subcluster of ASPCs that exhibit notable pro-inflammatory and proliferative characteristics. We identified four adipocyte subtypes, with one subtype showing a reduced lipid synthesis ability. Furthermore, iiFBs modulated the activities of macrophages and T cells in the IFP. Compared to subcutaneous and visceral adipose tissues, iiFBs represented a distinctive subpopulation of ASPCs in IFP that regulated cartilage proliferation through the MK pathway. CONCLUSION: This study presents a comprehensive single-cell transcriptomic atlas of IFP, uncovering its complex cellular landscape and potential impact on OA progression. Our findings highlight the role of iiFBs in OA, especially through MK pathway, opening new avenues for understanding OA pathogenesis and developing novel targeted therapies.


Subject(s)
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/pathology , Adipose Tissue/pathology , Knee Joint/pathology , Gene Expression Profiling , Fibroblasts/metabolism
15.
Clin Interv Aging ; 19: 255-263, 2024.
Article in English | MEDLINE | ID: mdl-38380228

ABSTRACT

Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.


Subject(s)
Frailty , Sleep Apnea, Obstructive , Humans , Aged , Middle Aged , Cohort Studies , Continuous Positive Airway Pressure , Frailty/epidemiology , Frailty/complications , Propensity Score , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/therapy
16.
ACS Appl Mater Interfaces ; 16(6): 7384-7398, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38308573

ABSTRACT

Flexible capacitive tactile sensors show great promise in personalized healthcare monitoring and human-machine interfaces, but their practical application is normally hindered because they rarely possess the required comprehensive performance, that is, high pressure sensitivity and fast response within a broad pressure range, high structure robustness, performance consistency, etc. This paper aims to engineer flexible capacitive pressure sensors with highly ordered porous dielectric microstructures and a 3D-printing-based fully solution-processable fabrication process. The proposed dielectric layer with uniformly distributed interior microporous can not only increase its compressibility and dynamic response within an extended pressure range but also enlarge its contact area with electrodes, contributing to a simultaneous improvement in the sensitivity, response speed, detection range, and structure robustness. Meanwhile, owing to its superior abilities in complex structure manufacturing and dimension controlling, the proposed 3D-printing-based fabrication process enables the consistent fabrication of the porous microstructure and thus guarantees device consistency. As a result, the prepared pressure sensors exhibit a high sensitivity of 0.21 kPa-1, fast response and relaxation times of 112 and 152 ms, an interface bonding strength of more than 455.2 kPa, and excellent performance consistency (≤5.47% deviation among different batches of sensors) and tunability. Encouraged by this, the pressure sensor is further integrated with a wireless readout circuit and realizes wireless wearable monitoring of various biosignals (pulse waves and heart rate) and body movements (from slight finger touch to large knee bending). Finally, the influence law of the feature parameters of the porous microstructure on device performance is established by the finite element method, paving the way for sensor optimization. This study motivates the development of flexible capacitive pressure sensors toward practical application.

17.
Nature ; 625(7995): 557-565, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38172636

ABSTRACT

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.


Subject(s)
Chondrocytes , NAV1.7 Voltage-Gated Sodium Channel , Osteoarthritis , Voltage-Gated Sodium Channel Blockers , Animals , Humans , Mice , Calcium/metabolism , Calcium Signaling/drug effects , Chondrocytes/drug effects , Chondrocytes/metabolism , Disease Progression , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , NAV1.7 Voltage-Gated Sodium Channel/deficiency , NAV1.7 Voltage-Gated Sodium Channel/genetics , NAV1.7 Voltage-Gated Sodium Channel/metabolism , Neurons/metabolism , Osteoarthritis/complications , Osteoarthritis/drug therapy , Osteoarthritis/genetics , Osteoarthritis/metabolism , Pain/complications , Pain/drug therapy , Pain/metabolism , Voltage-Gated Sodium Channel Blockers/pharmacology , Voltage-Gated Sodium Channel Blockers/therapeutic use
18.
Colloids Surf B Biointerfaces ; 234: 113742, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38271855

ABSTRACT

Because of the excellent performance in photochemistry, WO3 is increasingly applied in the field of biology and medicine. However, little is known about the mechanism of WO3 cytotoxicity. In this work, WO3 nanosheets with oxygen vacancy are synthesized by solvothermal method, then characterized and added to culture medium of human umbilical vein endothelial cells (HUVECs) with different concentrations. We characterized and analyzed the morphology of nano-WO3 by transmission electron microscopy and calculated the specific data of oxygen vacancy by XPS. It is the first time the effect of WO3-x on cells that WO3-x can cause oxidative stress in HUVEC cells, resulting in DNA damage and thus promoting apoptosis. Transcriptome sequencing is performed on cells treated with low and high concentrations of WO3-x, and a series of key signals affecting cell proliferation and apoptosis are detected in differentially expressed genes, which indicates the research direction of nanotoxicity. The expression levels of key genes are also verified by quantitative PCR after cell treatment with different concentrations of WO3-x. This work fills the gap between the biocompatibility of nano WO3-x materials and molecular cytology and paves the way for investigating the mechanism and risks of oxygen vacancy in cancer therapy.


Subject(s)
Oxides , Oxygen , Humans , Human Umbilical Vein Endothelial Cells , Oxides/chemistry , Tungsten/toxicity , Tungsten/chemistry
19.
Neurocrit Care ; 40(2): 743-749, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37697126

ABSTRACT

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.


Subject(s)
Cerebral Hemorrhage , Tomography, X-Ray Computed , Humans , Retrospective Studies , Prospective Studies , Cerebral Hemorrhage/complications , Hematoma/diagnostic imaging , Hematoma/therapy , Hematoma/complications
20.
Small ; 20(12): e2306318, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37948443

ABSTRACT

The development of excellently stretchable, highly mobile, and sustainable power supplies is of great importance for self-power wearable electronics. Transpiration-driven hydrovoltaic power generator (HPG) has been demonstrated to be a promising energy harvesting strategy with the advantages of negative heat and zero-carbon emissions. Herein, this work demonstrates a fiber-based stretchable HPG with the advantages of high output, portability, knittability, and sustainable power generation. Based on the functionalized micro-nano water diffusion channels constructed by the discarded mask straps (MSs) and oxidation-treated carbon nanomaterials, the applied water can continuously produce electricity during the spontaneous flow and diffusion. Experimentally, when a tiny 0.1 mL of water encounters one end of the proposed HPG, the centimeter-length device can yield a peak voltage of 0.43 V, peak current of 29.5 µA, and energy density of 5.833 mW h cm-3. By efficiently integrating multiple power generation units, sufficient output power can be provided to drive commercial electronic devices even in the stretched state. Furthermore, due to the reversibility of the electrical output during dynamic stretching-releasing, it can passively convert physiological activities and motion behaviors into quantifiable and processable current signals, opening up HPG's application in the field of self-powered wearable sensing.

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