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1.
Article in English | MEDLINE | ID: mdl-39092612

ABSTRACT

Polymer materials with multiple stimuli-responsive properties have demonstrated many potential and practical applications. By covalently introducing spiropyran (SP1) and spirothiopyran (STP) into the polyurethane backbone, photochromic, mechanochromic, and thermally discolored polymer materials have been prepared. In this work, we report for the first time that white light (violet, blue, and green light) above a certain intensity can activate STP to green color. Based on the above discovery, the polyurethane with SP1 and STP can exhibit reversible three-color changes (brown, green, and purple) in response to four stimuli: ultraviolet irradiation, white light irradiation, mechanical stress, and heat. The color-changing polymer materials have high color contrast and excellent reversibility, and can be used for reversible writing, anticounterfeiting and information encryption, etc.

3.
Cell Metab ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39084216

ABSTRACT

Adipose tissue can recruit catabolic adipocytes that utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-adipocytes and UCP1-beige adipocytes. Importantly, we demonstrate that the FC-adipocyte subpopulation is highly metabolically active and utilizes FCs to dissipate energy, thus contributing to thermogenesis independent of Ucp1. Furthermore, FC-adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.

4.
EBioMedicine ; 106: 105242, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39002385

ABSTRACT

BACKGROUND: Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. METHODS: Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N = 6 female) with severe obesity pre- and post-surgery. FINDINGS: The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from -11.5 to 10.8%; OVAT: 14,632 DMRs from -13.7 to 12.8%) than in blood (9267 DMRs from -8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49 regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. INTERPRETATION: Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery. FUNDING: The funding sources are listed in the Acknowledgments section.

5.
RSC Adv ; 14(32): 22877-22881, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39035717

ABSTRACT

Cellular mechanical force plays a crucial role in numerous biological processes, including wound healing, cell development, and metastasis. To enable imaging of intercellular tension, molecular tension probes were designed, which offer a simple and efficient method for preparing Au-DNA intercellular tension probes with universal applicability. The proposed approach utilizes gold nanoparticles linked to DNA hairpins, enabling sensitive visualization of cellular force in vitro. Specifically, the designed Au-DNA intercellular tension probe includes a molecular spring flanked by a fluorophore-quencher pair, which is anchored between cells. As intercellular forces open the hairpin, the fluorophore is de-quenched, allowing for visualization of cellular force. The effectiveness of this approach was demonstrated by imaging the cellular force in living cells using the designed Au-DNA intercellular tension probe.

6.
Nutr Diabetes ; 14(1): 52, 2024 07 11.
Article in English | MEDLINE | ID: mdl-38991999

ABSTRACT

OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.


Subject(s)
Follicle Stimulating Hormone , Luteinizing Hormone , Sex Hormone-Binding Globulin , Humans , Male , Follicle Stimulating Hormone/blood , Middle Aged , Adult , Luteinizing Hormone/blood , Risk Factors , Sex Hormone-Binding Globulin/metabolism , Sex Hormone-Binding Globulin/analysis , Estradiol/blood , Non-alcoholic Fatty Liver Disease/blood , China/epidemiology , Case-Control Studies , ROC Curve , Biomarkers/blood , Fatty Liver/blood , Aged
7.
Sci Rep ; 14(1): 16314, 2024 07 15.
Article in English | MEDLINE | ID: mdl-39009692

ABSTRACT

The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.


Subject(s)
Glucose , Graphite , Homeostasis , Infrared Rays , Physical Conditioning, Animal , Animals , Mice , Glucose/metabolism , Graphite/pharmacology , Graphite/chemistry , AMP-Activated Protein Kinases/metabolism , Male , Gastrointestinal Microbiome , Muscle, Skeletal/metabolism , Mice, Inbred C57BL , Hyperthermia, Induced/methods , Exercise Tolerance , Microbiota
8.
Nature ; 632(8024): 366-374, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38961294

ABSTRACT

Social communication guides decision-making, which is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odour from another animal in a social context, creating a long-term memory1,2. How food-preference memory is acquired, consolidated and stored is unclear. Here we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational centre in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signalling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm-mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. Our data thus define a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval.


Subject(s)
Memory, Long-Term , Olfactory Bulb , Animals , Memory, Long-Term/physiology , Male , Mice , Olfactory Bulb/physiology , Olfactory Bulb/cytology , Memory Consolidation/physiology , Synapses/physiology , Synapses/metabolism , Amygdala/physiology , Amygdala/cytology , Odorants/analysis , Social Behavior , Female , Single-Cell Analysis , Transcriptome , Mice, Inbred C57BL
9.
Talanta ; 278: 126480, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38972275

ABSTRACT

The prevalence of metabolic disorders has been found to increase concomitantly with alternations in habitual diet and lifestyle, indicating the importance of metabolic health monitoring for early warning of high-risk status and suggesting effective intervention strategies. Hippuric acid (HA), as one of the most abundant metabolites from the gut microbiota, holds potential as a regulator of metabolic health. Accordingly, it is imperative to establish an efficient, sensitive, and affordable method for large-scale population monitoring, revealing the association between HA level and metabolic disorders. Upon systematic screening of macrocycle•dye reporter pair, a supramolecular architecture (guanidinomethyl-modified calix[5]arene, GMC5A) was employed to sense urinary HA by employing fluorescein (Fl), whose complexation behavior was demonstrated by theoretical calculations, accomplishing quantification of HA in urine from 249 volunteers in the range of 0.10 mM and 10.93 mM. Excitedly, by restricted cubic spline, urinary HA concentration was found to have a significantly negative correlation with the risk of metabolic disorders when it exceeded 0.76 mM, suggesting the importance of dietary habits, especially the consumption of fruits, coffee, and tea, which was unveiled from a simple questionnaire survey. In this study, we accomplished a high throughput and sensitive detection of urinary HA based on supramolecular sensing with the GMC5A•Fl reporter pair, which sheds light on the rapid quantification of urinary HA as an indicator of metabolic health status and early intervention by balancing the daily diet.


Subject(s)
Biomarkers , Hippurates , Hippurates/urine , Humans , Biomarkers/urine , Male , Female , Adult , Middle Aged , Fluorescent Dyes/chemistry
10.
Cancer Lett ; 598: 217094, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38945204

ABSTRACT

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

11.
Cancer Lett ; 597: 217058, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38880226

ABSTRACT

OBJECTIVE: N6-methyladenosine (M6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of M6A modification. Methyltransferase promote the processing of mature miRNA in an M6A-dependent manner, thereby participating in disease occurrence and development. However, the regulatory mechanism of M6A in NK/T cell lymphoma (NKTCL) remains unclear. PATIENTS AND METHODS: We determined the expression of METTL3 and its correlation with clinicopathological features using qRT-PCR and immunohistochemistry. We evaluated the effects of METTL3 on NKTCL cells using dot blot assay, CCK8 assay and subcutaneous xenograft experiment. We then applied M6A sequencing combined with gene expression omnibus data to screen candidate targets of METTL3. Finally, we investigated the regulatory mechanism of METTL3 in NKTCL by methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays. RESULTS: We demonstrated that METTL3 was highly expressed in NKTCL cells and tissues and indicated poor prognosis. The METTL3 expression was associated with NKTCL survival. Functionally, METTL3 promoted the proliferation capability of NKTCL cells in vitro and in vivo. Furthermore, EBV-miR-BART3-3p was identified as the downstream effector of METTL3, and silencing EBV-miR-BART3-3p inhibited the proliferation of NKTCL. Finally, we confirmed that PLCG2 as a target gene of EBVmiR-BART3-3p by relative assays. CONCLUSIONS: We identified that METTL3 is significantly up-regulated in NKTCL and promotes NKTCL development. M6A modification contributes to the progression of NKTCL via the METTL3/EBV-miR-BART3-3p/PLCG2 axis. Our study is the first to report that M6A methylation has a critical role in NKTCL oncogenesis, and could be a potential target for NKTCL treatment.


Subject(s)
Adenosine , Cell Proliferation , Gene Expression Regulation, Neoplastic , Herpesvirus 4, Human , Lymphoma, Extranodal NK-T-Cell , Methyltransferases , MicroRNAs , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Lymphoma, Extranodal NK-T-Cell/genetics , Lymphoma, Extranodal NK-T-Cell/virology , Lymphoma, Extranodal NK-T-Cell/pathology , Lymphoma, Extranodal NK-T-Cell/metabolism , Animals , Adenosine/analogs & derivatives , Adenosine/metabolism , Mice , Female , Male , Herpesvirus 4, Human/genetics , Cell Line, Tumor , Methylation , Prognosis , Middle Aged , Mice, Nude , Xenograft Model Antitumor Assays
12.
Chem Sci ; 15(22): 8506-8513, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38846396

ABSTRACT

The modulation of emission color is one of the most critical topics in the research field of organic light-emitting diodes (OLEDs). Currently, only two ways are commonly used to tune the emission colors of OLEDs: one is to painstakingly synthesize different emitters with diverse molecular structures, the other is to precisely control the degree of aggregation or doping concentration of one emitter. To develop a simpler and less costly method, herein we demonstrate a new strategy in which the emission colors of OLEDs can be continuously changed with UV light during the device fabrication process. The proof of concept is established by a chromene-based Ir(iii) complex, which shows bright green emission and yellow emission before and after UV irradiation, respectively. Consequently, under different durations of UV irradiation, the resulting Ir(iii) complex is successfully used as the emitter to gradually tune the emission colors of related solution-processed OLEDs from green to yellow. Furthermore, the electroluminescent efficiencies of these devices are unaffected or even increased during this process. Therefore, this work demonstrates a distinctive point of view and approach for modulating the emission colors of OLEDs, which may prove great inspiration for the fabrication of multi-colored OLEDs with only one emitter.

13.
Oncol Lett ; 28(2): 377, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38939622

ABSTRACT

[This retracts the article DOI: 10.3892/ol.2017.6728.].

14.
Water Res ; 257: 121695, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38723352

ABSTRACT

Wolframite (FeWO4), a typical polyoxometalate, serves as an auspicious candidate for heterogeneous catalysts, courtesy of its high chemical stability and electronic properties. However, the electron-deficient surface-active Fe species in FeWO4 are insufficient to cleave H2O2 via Fe redox-mediated Fenton-like catalytic reaction. Herein, we doped Sulfur (S) atom into FeWO4 catalysts to refine the electronic structure of FeWO4 for H2O2 activation and sulfamethoxazole (SMX) degradation. Furthermore, spin-state reconstruction on S-doped FeWO4 was found to effectively refine the electronic structure of Fe in the d orbital, thereby enhancing H2O2 activation. S doping also accelerated electron transfer during the conversion of sulfur species, promoting the cycling of Fe(III) to Fe(II). Consequently, S-doped FeWO4 bolstered the Fenton-like reaction by nearly two orders of magnitude compared to FeWO4. Significantly, the developed S-doped FeWO4 exhibited a remarkable removal efficiency of approximately 100% for SMX within 40 min in real water samples. This underscores its extensive pH adaptability, robust catalytic stability, and leaching resistance. The matrix effects of water constituents on the performance of S-doped FeWO4 were also investigated, and the results showed that a certain amount of Cl-, SO42-, NO3-, HCO3- and PO43- exhibited negligible effects on the degradation of SMX. Theoretical calculations corroborate that the distinctive spin-state reconstruction of Fe center in S-doped FeWO4 is advantageous for H2O2 decomposition. This discovery offers novel mechanistic insight into the enhanced catalytic activity of S doping in Fenton-like reactions and paves the way for expanding the application of FeWO4 in wastewater treatment.


Subject(s)
Sulfur , Water Pollutants, Chemical , Sulfur/chemistry , Water Pollutants, Chemical/chemistry , Tungsten Compounds/chemistry , Hydrogen Peroxide/chemistry , Catalysis , Water Purification/methods , Oxidation-Reduction , Iron/chemistry
15.
World J Gastrointest Surg ; 16(4): 1184-1188, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38690059

ABSTRACT

BACKGROUND: Splenic rupture associated with Behçet's syndrome (BS) is extremely rare, and there is no consensus on its management. In this case report, a patient with BS-associated splenic rupture was successfully treated with splenic artery embolization (SAE) and had a good prognosis after the intervention. CASE SUMMARY: The patient was admitted for pain in the left upper abdominal quadrant. He was diagnosed with splenic rupture. Multiple oral and genital aphthous ulcers were observed, and acne scars were found on his back. He had a 2-year history of BS diagnosis, with symptoms of oral and genital ulcers. At that time, he was treated with oral corticosteroids for 1 month, but the symptoms did not alleviate. He underwent SAE to treat the rupture. On the first day after SAE, the patient reported a complete resolution of abdominal pain and was discharged 5 d later. Three months after the intervention, a computed tomography examination showed that the splenic hematoma had formed a stable cystic effusion, suggesting a good prognosis. CONCLUSION: SAE might be a good choice for BS-associated splenic rupture based on good surgical practice and material selection.

16.
Eur Urol Oncol ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38762368

ABSTRACT

BACKGROUND AND OBJECTIVE: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). METHODS: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0. KEY FINDINGS AND LIMITATIONS: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs. CONCLUSIONS: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC. PATIENT SUMMARY: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.

17.
Sci Rep ; 14(1): 12166, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806604

ABSTRACT

In recent years, with the unremitting advancement of higher education reform, academics have been experiencing stress associated with conducting scientific research. In this study focusing on university teachers in China, we adopted a stepwise regression method and reviewed related literature to construct a mechanism of academic stress and occupational burnout. Specifically, we tested job satisfaction and relative deprivation as mediating and moderating variables and conducted empirical research on 1239 teachers from 15 universities in eastern, central, and western China. Our findings show that: (1) academic stress has a significant positive effect on occupational burnout; (2) job satisfaction has a partial role as the intermediary agent between academic stress and occupational burnout; and (3) relative deprivation positively moderates the relationship between academic stress and job satisfaction, indicating that teachers in universities and colleges are also affected by relative deprivation and the perception of inequity. These findings have significant value in the management of higher education and academic research.


Subject(s)
Burnout, Professional , Job Satisfaction , Humans , China/epidemiology , Universities , Burnout, Professional/psychology , Burnout, Professional/epidemiology , Male , Female , Adult , Faculty/psychology , Stress, Psychological/psychology , Surveys and Questionnaires , Middle Aged
18.
Heliyon ; 10(8): e29577, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38655341

ABSTRACT

The rapid advancement of Micro-Electro-Mechanical Systems (MEMS) technology has established microfluidics as a pivotal field. This technology marks the onset of a new era in various applications, including drug testing, cell culture, and disease monitoring, underscoring its extensive practicality and potential for future exploration. This research delves into the intricate behavior of particle inertial migration within microchannels, particularly focusing on the impact of different channel structures and Reynolds numbers (Re). Our studies reveal that particles in microchannels with one-sided sharp-cornered microstructures migrate towards the sharp corner at a relative position of 0.4 under low flow rates, and towards the straight wall side at a relative position of 0.8 under high flow rates. The migration pattern of equilibrium positions varies with different arrangements of sharp-corner structures, achieving stability at the channel's center only when the sharp corners are symmetrically arranged on both sides. Our investigation into the shape of microstructures indicates that sharp-cornered structures generate a more stable secondary flow compared to rectangular and semi-circular structures, preventing particle aggregation at the outlet. To address the challenges associated with handling variable cross-section geometries and solid-wall boundaries in dissipative particle dynamics methods effectively, we have developed a dissipative particle dynamics model specifically for analyzing such microchannels. Building upon our previous research, this model introduces a conservative force coefficient for particles within the microstructured region and an interaction zone that only involves repulsive forces, aligning well with experimental outcomes. Through the study of microstructures' geometric shapes, this paper offers guidance for designing microchannels for particle enrichment. Furthermore, the dissipative particle dynamics model established for the particle flow and solid structure interaction within microstructured channels provides insights into the mesoscale dynamics of liquid-solid two-phase flow and particle motion. In conclusion, this paper aims to enhance particle motion sample preparation techniques, thereby broadening the scope of microfluidic applications in the biomedical field.

19.
Mol Neurobiol ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38664301

ABSTRACT

Neuroinflammation is a common pathological feature in a number of neurodegenerative diseases, which is mediated primarily by the activated glial cells. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome-associated neuroinflammatory response is mostly considered. To investigate the situation of the NLRP3-related inflammation in prion disease, we assessed the levels of the main components of NLRP3 inflammasome and its downstream biomarkers in the scrapie-infected rodent brain tissues. The results showed that the transcriptional and expressional levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein (ASC) in the brains of scrapie-infected rodents were significantly increased at terminal stage. The increased NLPR3 overlapped morphologically well with the proliferated GFAP-positive astrocytes, but little with microglia and neurons. Using the brain samples collected at the different time-points after infection, we found the NLRP3 signals increased in a time-dependent manner, which were coincidental with the increase of GFAP. Two main downstream cytokines, IL-1ß and IL-18, were also upregulated in the brains of prion-infected mice. Moreover, the gasdermin D (GSDMD) levels, particularly the levels of GSDMD-NT, in the prion-infected brain tissues were remarkably increased, indicating activation of cell pyroptosis. The GSDMD not only co-localized well with the astrocytes but also with neurons at terminal stage, also showing a time-dependent increase after infection. Those data indicate that NLRP3 inflammasomes were remarkably activated in the infected brains, which is largely mediated by the proliferated astrocytes. Both astrocytes and neurons probably undergo a pyroptosis process, which may help the astrocytes to release inflammatory factors and contribute to neuron death during prion infection.

20.
J Chromatogr A ; 1723: 464716, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38640881

ABSTRACT

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.


Subject(s)
Drugs, Chinese Herbal , Glucosides , Monoterpenes , Rats, Sprague-Dawley , Saponins , Tandem Mass Spectrometry , Triterpenes , Animals , Glucosides/pharmacokinetics , Glucosides/analysis , Glucosides/chemistry , Glucosides/pharmacology , Saponins/pharmacokinetics , Saponins/pharmacology , Saponins/chemistry , Saponins/analysis , Monoterpenes/analysis , Triterpenes/pharmacology , Triterpenes/pharmacokinetics , Triterpenes/chemistry , Triterpenes/analysis , Dogs , Rats , Madin Darby Canine Kidney Cells , Tandem Mass Spectrometry/methods , Male , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Apiaceae/chemistry , Herb-Drug Interactions , Drug Interactions , Reproducibility of Results
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