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1.
Chem Commun (Camb) ; 60(59): 7614-7617, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38957034

ABSTRACT

A mild and efficient electrochemical method for radical addition, cyclization, and migration reaction was described in this work. A difluoromethyl radical was produced by anodizing CF2HSO2Na. The resulting product was then added to olefin, underwent Smiles cyclization, and migrated to form ß-difluoromethamide compounds after the release of SO2. The process was free from metals and catalysts, gram-grade, and resistant to a variety of electron-rich substrates.

2.
BMC Urol ; 24(1): 144, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997703

ABSTRACT

BACKGROUND: Prostate cancer, characterized by its insidious onset and short overall survival, and has seen a rise in incidence over recent decades. This study aims to investigate the expression and molecular mechanism of lncRNA PTCSC3 (PTCSC3) in prostate cancer in order to develop new prognostic and therapeutic biomarkers. METHODS: The level of PTCSC3 in serum and cell samples of prostate cancer was quantitatively measured using RT-qPCR assays. The correlation between the variation in PTCSC3 levels and clinical indicators of patients was evaluated. The survival status of the prostate cancer patients included in the study was evaluated using Kaplan-Meier curve and multivariable Cox analysis. The impact of PTCSC3 overexpression on cell growth and activity was revealed by CCK-8 and Transwell assays. The targeting relationship between PTCSC3 and miR-182-5p was determined by bioinformatics prediction and luciferase activity. RESULTS: PTCSC3 was found to be downregulated in prostate cancer, and its low levels were associated with short overall survival in patients. It influenced the progression of prostate cancer by targeting miR-182-5p. Increasing PTCSC3 levels suppressed the proliferation, migration and invasion levels of cells, and miR-182-5p mimic counteracted PTCSC3's effects on cells. CONCLUSIONS: As a potential prognostic biological factor for prostate cancer, PTCSC3 may regulate the progression of prostate cancer by sponging miR-182-5p and affect the prognosis of patients.


Subject(s)
MicroRNAs , Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/blood , Prognosis , RNA, Long Noncoding/genetics , RNA, Long Noncoding/blood , Middle Aged , Aged , Survival Rate , Down-Regulation
3.
World J Exp Med ; 14(2): 90481, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38948414

ABSTRACT

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

4.
Inflammation ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913145

ABSTRACT

It has recently become more recognized that renal diseases in adults can originate from adverse intrauterine (maternal) environmental exposures. Previously, we found that prenatal lipopolysaccharide (LPS) exposure can result in chronic renal inflammation, which leads to renal damage in older offspring rats. To test whether prenatal inflammatory exposure predisposes offspring to renal damage, a mouse model of oral adenine consumption-induced chronic kidney disease (CKD) was applied to offspring from prenatal LPS-treated mothers (offspring-pLPS) and age-matched control offspring of prenatal saline-treated mothers (offspring-pSaline). We found that offspring-pLPS mice presented with more severe renal collagen deposition and renal dysfunction after 4 weeks of adenine consumption than sex- and treatment-matched offspring-pSaline controls. To illustrate the underlying molecular mechanism, we subjected offspring-pLPS and offspring-pSaline kidneys to genome-wide transcriptomic analysis. Bioinformatic analysis of the sequencing data, together with further experimental confirmation, revealed a strong activation of the PERK-eIF2α-ATF4-mediated unfolded protein response (UPR) in offspring-pLPS kidneys, which likely contributed to the CKD predisposition seen in offspring-pLPS mice. More importantly, the specific eIF2α-ATF4 signaling inhibitor ISIRB was able to prevent adenine-induced CKD in the offspring-pLPS mice. Our findings suggest that the eIF2α-ATF4-mediated UPR, but not PERK, is likely the major disease-causing pathway in prenatal inflammatory exposure-induced CKD predisposition. Our study also suggests that targeting this signaling pathway is a potentially promising approach for CKD treatment.

5.
BMC Health Serv Res ; 24(1): 706, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840121

ABSTRACT

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease that can cause multiple organ damage in the whole body. Our aim was to use machine learning (ML) to build an independent polysomnography (PSG) model to analyze risk factors and predict OSAHS. MATERIALS AND METHODS: Clinical data of 2064 snoring patients who underwent physical examination in the Health Management Center of the First Affiliated Hospital of Shanxi Medical University from July 2018 to July 2023 were retrospectively collected, involving 24 characteristic variables. Then they were randomly divided into training group and verification group according to the ratio of 7:3. By analyzing the importance of these features, it was concluded that LDL-C, Cr, common carotid artery plaque, A1c and BMI made major contributions to OSAHS. Moreover, five kinds of machine learning algorithm models such as logistic regression, support vector machine, Boosting, Random Forest and MLP were further established, and cross validation was used to adjust the model hyperparameters to determine the final prediction model. We compared the accuracy, Precision, Recall rate, F1-score and AUC indexes of the model, and finally obtained that MLP was the optimal model with an accuracy of 85.80%, Precision of 0.89, Recall of 0.75, F1-score of 0.82, and AUC of 0.938. CONCLUSION: We established the risk prediction model of OSAHS using ML method, and proved that the MLP model performed best among the five ML models. This predictive model helps to identify patients with OSAHS and provide early, personalized diagnosis and treatment options.


Subject(s)
Machine Learning , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/diagnosis , Male , Female , Middle Aged , Adult , Retrospective Studies , Risk Factors , Risk Assessment/methods , Polysomnography
6.
Small ; : e2401996, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829026

ABSTRACT

Visible-blind ultraviolet (UV) light detection has a wide application range in scenes like space environment monitoring and medical imaging. To realize miniaturized UV detectors with high performance and high integration ability, new device structures without bulky light filters need to be developed based on advanced mechanisms. Here the unipolar barrier van der Waals heterostructure (UB-vdWH) photodetector is reported that realizes filter-free visible-blind UV detection with good stability, robustness, selectivity, and high detection performance. The UB-vdWH shows a responsivity of 2452 A W-1, a photo on-off ratio of 2.94 × 105 and a detectivity of 1.26 × 1015 Jones as a UV detector, owing to the intentionally designed barrier height that suppresses dark current and photoresponse to visible light during the transport process. The good performance remains intact during 104 test cycles or even under high temperatures, which proves the stability, and robustness of the UB-vdWH, thus shows the huge potential for a wider application range.

7.
BMC Psychiatry ; 24(1): 452, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890607

ABSTRACT

BACKGROUND: Getting lost with family members who have dementia is a significant source of stress for family caregivers. In Taiwan, family caregivers develop strategies to deal with dementia persons who may get lost. This study aimed to explore the experiences of family caregivers caring for persons with dementia who have been lost outside the home. METHODS: A descriptive phenomenological method was used. The COREQ checklist was used to ensure the explicit reporting of data. A total of 20 family caregivers caring for persons with dementia who were lost outside their homes were selected from hospital outpatient clinics and a day care center in northern Taiwan using purposive sampling. Data were analyzed using the Giorgi analysis method. RESULTS: Five main themes emerged: (i) surprised persons with dementia lost outside, (ii) using strategies to prevent persons with dementia from getting lost, (iii) using strategies to find lost persons with dementia, (iv) exhaustion in long-term care persons with dementia, and (v) coping with the care load. It was found that family caregivers were surprised, nervous, and worried about persons with dementia being lost outside. They used the first strategy to supervise persons with dementia to prevent external losses. In addition, long-term supervision of persons with dementia led to mental exhaustion in the family caregivers. Finally, the family caregivers learned about loss prevention strategies and obtained family support and care replacement workers to reduce the care burden. CONCLUSIONS: It is essential to teach family caregivers early to prevent persons with dementia from losing external strategies. Nurses also provide long-term care services to reduce the care burden on family caregivers.


Subject(s)
Adaptation, Psychological , Caregivers , Dementia , Qualitative Research , Humans , Caregivers/psychology , Dementia/nursing , Dementia/psychology , Male , Female , Middle Aged , Aged , Taiwan , Family/psychology , Adult , Stress, Psychological/psychology , Aged, 80 and over
8.
Chem Commun (Camb) ; 60(53): 6773-6776, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38864654

ABSTRACT

A novel phosphine-mediated α-umpolung/Wittig olefination/cyclization cascade process between o-aminobenzaldehydes and Morita-Baylis-Hillman (MBH) carbonates has been ingeniously developed. This protocol serves as a practical tool for the facile synthesis of a broad range of 2-vinylindolines in moderate to good yields under mild reaction conditions. The applicability of this method was demonstrated with gram-scale reaction and various transformations of the corresponding product.

9.
Adv Sci (Weinh) ; 11(28): e2402846, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38757635

ABSTRACT

Organic near-infrared (NIR) room temperature phosphorescence (RTP) materials become a hot topic in bioimaging and biosensing for the large penetration depth and high signal-to-background ratio (SBR). However, it is challenging to achieve persistent NIR phosphorescence for severe nonradiative transitions by energy-gap law. Herein, a universal system with persistent NIR RTP is built by visible (host) and NIR phosphorescence (guest) materials, which can efficiently suppress the nonradiative transitions by rigid environment of crystalline host materials with good matching, and further promote phosphorescence emission by the additional phosphorescence resonance energy transfer (≈100%) between them. The persistent NIR phosphorescence with ten-folds enhancement of RTP lifetimes, compared to those of guest luminogens, can be achieved by modulation of aggregated structures of host-guest systems. This work provides a convenient way to largely prolong the phosphorescence lifetimes of various NIR luminogens, promoting their application in afterglow imaging with deeper penetration and higher SBRs.

10.
J Psychiatr Res ; 175: 20-28, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38701608

ABSTRACT

Cell-free DNA (cfDNA) has been found to be elevated in patients with schizophrenia (SZ), potentially derived from activated apoptosis, but the underlying mechanisms remain unknown. Moreover, whether the concentrations of cfDNA are altered with disease stage has not been investigated, which limits its clinical application as an auxiliary diagnostic marker for SZ. Using an improved fluorescence correlation spectroscopy (FCS) method that does not require DNA extraction, we measured the molar concentrations of cfDNA in plasma samples of 191 patients with SZ, 78 patients with mood disorders (MD) and 65 healthy controls (HC). We also analyzed the cfDNA composition from either the nucleus or mitochondria, oxidation markers and biochemical indexes to explore the potential mechanistic associations of the increased cfDNA levels. We found that in SZ patients, the cfDNA levels were significantly increased (P = 0.003) regardless of the different disease stages or antipsychotic medication use. Furthermore, qPCR revealed that cell-free nuclear DNA (cf-nDNA) (P = 0.041) but not cell-free mitochondrial DNA (cf-mtDNA) was elevated in SZ patients. Moreover, decreased SOD activity in SZ patients (P = 0.005) was negatively correlated with cfDNA levels (P = 0.047), and fasting blood glucose was positively correlated with cfDNA levels in SZ patients (P = 0.013). Our study provides evidence to support that the elevated cfDNA may be a convenient, effective and stable trait indicator of SZ. Further analysis showed that it mainly came from nucleus, suggesting increased apoptosis, and potentially related to oxidative stress and high blood glucose levels in patients.

11.
Nano Lett ; 24(19): 5862-5869, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38709809

ABSTRACT

Dynamic vision perception and processing (DVPP) is in high demand by booming edge artificial intelligence. However, existing imaging systems suffer from low efficiency or low compatibility with advanced machine vision techniques. Here, we propose a reconfigurable bipolar image sensor (RBIS) for in-sensor DVPP based on a two-dimensional WSe2/GeSe heterostructure device. Owing to the gate-tunable and reversible built-in electric field, its photoresponse shows bipolarity as being positive or negative. High-efficiency DVPP incorporating front-end RBIS and back-end CNN is then demonstrated. It shows a high recognition accuracy of over 94.9% on the derived DVS128 data set and requires much fewer neural network parameters than that without RBIS. Moreover, we demonstrate an optimized device with a vertically stacked structure and a stable nonvolatile bipolarity, which enables more efficient DVPP hardware. Our work demonstrates the potential of fabricating DVPP devices with a simple structure, high efficiency, and outputs compatible with advanced algorithms.

12.
Clin Exp Pharmacol Physiol ; 51(6): e13866, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719209

ABSTRACT

Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.


Subject(s)
Histone Deacetylase 6 , Histone Deacetylase Inhibitors , Macrophages , Reactive Oxygen Species , Staphylococcus aureus , Animals , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase 6/metabolism , Reactive Oxygen Species/metabolism , Staphylococcus aureus/drug effects , Mice , Macrophages/drug effects , Macrophages/metabolism , Macrophages/microbiology , Histone Deacetylase Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Pneumonia, Staphylococcal/drug therapy , Pneumonia, Staphylococcal/microbiology , Pneumonia, Staphylococcal/metabolism , Indoles/pharmacology , Mice, Inbred C57BL , Phagocytosis/drug effects , Lung/drug effects , Lung/microbiology , Lung/metabolism , Lung/pathology
13.
Clin Oral Investig ; 28(6): 311, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743171

ABSTRACT

OBJECTIVE: This study used image-based finite element analysis (FEA) to assess the biomechanical changes in mandibular first molars resulting from alterations in the position of the root canal isthmus. METHODS: A healthy mandibular first molar, characterized by two intact root canals and a cavity-free surface, was selected as the subject. A three-dimensional model for the molar was established using scanned images of the patient's mandibular teeth. Subsequently, four distinct finite element models were created, each representing varied root canal morphologies: non-isthmus (Group A), isthmus located at the upper 1/3 of the root (Group B), middle 1/3 of the root (Group C), and lower 1/3 of the root (Group D). A static load of 200 N was applied along the tooth's longitudinal axis on the occlusal surface to simulate regular chewing forces. The biomechanical assessment was conducted regarding the mechanical stress profile within the root dentin. The equivalent stress (Von Mises stress) was used to assess the biomechanical features of mandibular teeth under mechanical loading. RESULTS: In Group A (without an isthmus), the maximum stress was 22.2 MPa, while experimental groups with an isthmus exhibited higher stresses, reaching up to 29.4 MPa. All maximum stresses were concentrated near the apical foramen. The presence of the isthmus modified the stress distribution in the dentin wall of the tooth canal. Notably, dentin stresses at specific locations demonstrated differences: at 8 mm from the root tip, Group B: 13.6 MPa vs. Group A: 11.4 MPa; at 3 mm from the root tip, Group C: 14.2 MPa vs. Group A: 4.5 MPa; at 1 mm from the root tip, Group D: 25.1 MPa vs. Group A: 10.3 MPa. The maximum stress in the root canal dentin within the isthmus region was located either at the top or bottom of the isthmus. CONCLUSION: A root canal isthmus modifies the stress profile within the dentin. The maximum stress occurs near the apical foramen and significantly increases when the isthmus is located closer to the apical foramina.


Subject(s)
Dental Pulp Cavity , Dental Stress Analysis , Finite Element Analysis , Mandible , Molar , Humans , Biomechanical Phenomena , Dental Pulp Cavity/anatomy & histology , Dental Stress Analysis/methods , Imaging, Three-Dimensional/methods , Stress, Mechanical
14.
AAPS J ; 26(3): 56, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671158

ABSTRACT

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R1, R2, T1, T2) of Advair Diskus (100 µg FP/50 µg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R1 and R2 confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUCinf) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1 µm, < 2 µm) had a higher AUCinf. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.


Subject(s)
Bronchodilator Agents , Cross-Over Studies , Dry Powder Inhalers , Fluticasone-Salmeterol Drug Combination , Models, Biological , Therapeutic Equivalency , Humans , Administration, Inhalation , Male , Adult , Fluticasone-Salmeterol Drug Combination/pharmacokinetics , Fluticasone-Salmeterol Drug Combination/administration & dosage , Young Adult , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/blood , Female , Middle Aged , Fluticasone/pharmacokinetics , Fluticasone/administration & dosage , Salmeterol Xinafoate/pharmacokinetics , Salmeterol Xinafoate/administration & dosage , Healthy Volunteers
15.
Discov Oncol ; 15(1): 113, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605206

ABSTRACT

PURPOSE: The purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer. METHODS: RT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan-Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays. RESULTS: It was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer. CONCLUSION: DSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

16.
Ying Yong Sheng Tai Xue Bao ; 35(1): 203-211, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38511457

ABSTRACT

Liangshan Prefecture is one of the three major forest areas in Sichuan Province and one of the three major disaster areas of forest fire. We measured the physicochemical properties and combustion performances of different organs (leaves and branches) of 15 main economic tree species in Liangshan, and analyzed the bioecology characteristics, silviculture characteristics and value characteristics of different tree species. We investigated the fire resistance of different tree species to screen out fire-resistant species suitable for economic forest development in Liangshan Prefecture, and improve the biological fire prevention ability. The seven physicochemical properties and combustion performances indices of 15 tree species showed significant differences. Except for crude ash and lignin, the weights of moisture content, caloric value, ignition point, crude fat, and crude fibre of leaves were higher than those of branches. Crude fibre index of leaves (9.6%) and the crude ash index of branches (9.9%) were the highest weight indices of the two organs, respectively. Based on the fire resistance, we divided all the species into three classes, i.e., class Ⅰ (excellent fire-resistance trees) Juglans regia and Morus alba; class Ⅱ (better fire-resistant trees) Sapium sebiferum, Mangifera indica, Phyllanthus emblica, Eriobotrya japonica, Ligustrum lucidum, Castanea mollissima, and Punica granatum; class Ⅲ (poor fire-resistant trees) Pinus armandii, Illicium simonsii, Morella rubra, Sapindus mukorossi, Olea europaea and Camellia oleifera. J. regia and M. alba had fireproof solid performance and could be used as the preferred species for fireproof economic forest in Liangshan region. It was suggested that to use class Ⅰ to Ⅱ fire-resistant tree species built the main fireproof isolated forest belt, and pay attention to fire prevention after planting class Ⅲ tree species in a large area.


Subject(s)
Fires , Wildfires , Trees , Forests , China
17.
Anal Bioanal Chem ; 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38459966

ABSTRACT

The high catalytic activity of Cu-based nanozymes mainly depends on the efficient Fenton-like reaction of Cu+/ H2O2, but Cu+ cannot exist stably. Trying to find a material that can stably support Cu+ while promoting the electron cycle of Cu2+/Cu+ still faces serious challenges. C60 is expected to be an ideal candidate to solve this problem due to its unique structure and rich physicochemical properties. Here, we designed and synthesized a C60-doped Cu+-based nanozyme (termed as C60-Cu-Bpy) by loading high catalytic active site Cu+ onto C60 and coordinating with 2,2'-bipyridine (Bpy). The single crystal diffraction analysis and a series of auxiliary characterization technologies were used to demonstrate the successful preparation of C60-Cu-Bpy. Significantly, the C60-Cu-Bpy exhibited superior peroxidase-like activity during the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Then, the catalytic mechanism of C60-Cu-Bpy as peroxidase was elucidated in detail, mainly benefiting from the dual function of C60. On the one hand, C60 acted as a carrier to directly support Cu+, which has the ability to efficiently decompose H2O2 to produce reactive oxygen species. The other was that C60 acted as an electron buffer, contributing to promoting the Cu2+/Cu+ cycle to facilitate the reaction. Furthermore, a colorimetric sensor for the quantitative analysis of bleomycin was established based on the principle of bleomycin specific inhibition of C60-Cu-Bpy peroxidase-like activity, with satisfactory results in practical samples. This study provides a new strategy for the direct synthesis of Cu+-based nanozymes with high catalytic performance.

18.
Inflammation ; 47(2): 789-806, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38446361

ABSTRACT

Altered cardiac innate immunity is highly associated with the progression of cardiac disease states and heart failure. S100A8/A9 is an important component of damage-associated molecular patterns (DAMPs) that is critically involved in the pathogenesis of heart failure, thus considered a promising target for pharmacological intervention. In the current study, initially, we validated the role of S100A8/A9 in contributing to cardiac injury and heart failure via the overactivation of the ß-adrenergic pathway and tested the potential use of paquinimod as a pharmacological intervention of S100A8/A9 activation in preventing cardiac dysfunction, collagen deposition, inflammation, and immune cell infiltration in ß-adrenergic overactivation-mediated heart failure. This finding was further confirmed by the cardiomyocyte-specific silencing of S100A9 via the use of the adeno-associated virus (AAV) 9-mediated short hairpin RNA (shRNA) gene silencing system. Most importantly, in the assessment of the underlying cellular mechanism by which activated S100A8/A9 cause aggravated progression of cardiac fibrosis and heart failure, we discovered that the activated S100A8/A9 can promote fibroblast-macrophage interaction, independent of inflammation, which is likely a key mechanism leading to the enhanced collagen production. Our results revealed that targeting S100A9 provides dual beneficial effects, which is not only a strategy to counteract cardiac inflammation but also preclude cardiac fibroblast-macrophage interactions. The findings of this study also indicate that targeting S100A9 could be a promising strategy for addressing cardiac fibrosis, potentially leading to future drug development.


Subject(s)
Calgranulin B , Myocytes, Cardiac , Animals , Mice , Adrenergic beta-Agonists/pharmacology , Calgranulin A/metabolism , Calgranulin B/metabolism , Calgranulin B/genetics , Fibroblasts/metabolism , Fibroblasts/drug effects , Fibrosis , Heart Failure/metabolism , Heart Failure/prevention & control , Inflammation/metabolism , Macrophages/metabolism , Macrophages/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology
19.
Autophagy ; 20(7): 1651-1672, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38433354

ABSTRACT

Macroautophagy/autophagy-mediated anoikis resistance is crucial for tumor metastasis. As a key autophagy-related protein, ATG4B has been demonstrated to be a prospective anti-tumor target. However, the existing ATG4B inhibitors are still far from clinical application, especially for tumor metastasis. In this study, we identified a novel circRNA, circSPECC1, that interacted with ATG4B. CircSPECC1 facilitated liquid-liquid phase separation of ATG4B, which boosted the ubiquitination and degradation of ATG4B in gastric cancer (GC) cells. Thus, pharmacological addition of circSPECC1 may serve as an innovative approach to suppress autophagy by targeting ATG4B. Specifically, the circSPECC1 underwent significant m6A modification in GC cells and was subsequently recognized and suppressed by the m6A reader protein ELAVL1/HuR. The activation of the ELAVL1-circSPECC1-ATG4B pathway was demonstrated to mediate anoikis resistance in GC cells. Moreover, we also verified that the above pathway was closely related to metastasis in tissues from GC patients. Furthermore, we determined that the FDA-approved compound lopinavir efficiently enhanced anoikis and prevented metastasis by eliminating repression of ELAVL1 on circSPECC1. In summary, this study provides novel insights into ATG4B-mediated autophagy and introduces a viable clinical inhibitor of autophagy, which may be beneficial for the treatment of GC with metastasis.


Subject(s)
Anoikis , Autophagy , Cysteine Endopeptidases , Lopinavir , RNA, Circular , Anoikis/drug effects , Autophagy/drug effects , Humans , RNA, Circular/metabolism , RNA, Circular/genetics , Cell Line, Tumor , Cysteine Endopeptidases/metabolism , Lopinavir/pharmacology , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Autophagy-Related Proteins/metabolism , Animals , Mice , Ubiquitination/drug effects
20.
Sensors (Basel) ; 24(4)2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38400472

ABSTRACT

Because of its uneven and large slope, unstructured pavement presents a great challenge to obtaining the adhesion coefficient of pavement. An estimation method of the peak adhesion coefficient of unstructured pavement on the basis of the extended Kalman filter is proposed in this paper. The identification accuracy of road adhesion coefficients under unstructured pavement is improved by introducing the equivalent suspension model to optimize the calculation of vertical wheel load and modifying vehicle acceleration combined with vehicle posture data. Finally, the multi-condition simulation experiments with Carsim are conducted, the estimation accuracy of the adhesion coefficient is at least improved by 3.6%, and then the precision and effectiveness of the designed algorithm in the article are verified.

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