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1.
Article in English | MEDLINE | ID: mdl-38960805

ABSTRACT

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

2.
Sci Rep ; 14(1): 15175, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956251

ABSTRACT

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin-eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia-reperfusion injury.


Subject(s)
Copper , Disulfiram , Homeostasis , Inflammation , Mice, Inbred C57BL , Reperfusion Injury , Animals , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , Disulfiram/pharmacology , Mice , Copper/metabolism , Homeostasis/drug effects , Male , Inflammation/metabolism , Inflammation/drug therapy , Inflammation/pathology , Down-Regulation/drug effects , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Disease Models, Animal , Iron-Sulfur Proteins/metabolism , Brain Ischemia/metabolism , Brain Ischemia/drug therapy , Brain Ischemia/pathology , Apoptosis/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Neuroprotective Agents/pharmacology , Toll-Like Receptor 4/metabolism
3.
Animals (Basel) ; 14(13)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38998118

ABSTRACT

The selection of proper reference genes is vital for ensuring precise quantitative real-time PCR (qPCR) assays. This study evaluates the stability of the expression of nine candidate reference genes in different tissues and during testicular development in H. labeo. The results show that eef1a is recommended as a reference gene for qPCR analysis in tissues and during testicular development. Furthermore, we evaluated the optimal number of reference genes needed when calculating gene expression levels using the geomean method, revealing that two reference genes are sufficient. Specifically, eef1a and rps27 are recommended for analysis of gene expression in tissues, whereas eef1a and actb are advised for evaluating gene expression during testicular development. In addition, we examined the expression pattern of kifc1, a kinesin involved in the reshaping of spermatids. We detected peak expression levels of kifc1 in testes, with its expression initially increasing before decreasing throughout testicular development. The highest expression of kifc1 was observed in stage IV testes, the active period of spermiogenesis, suggesting a possible role for kifc1 in the regulation of the reshaping of spermatids and hence testicular development. This study represents the first investigation of reference genes for H. labeo, providing a foundation for studying gene expression patterns and investigating gene expression regulation during testicular development.

4.
Front Microbiol ; 15: 1385992, 2024.
Article in English | MEDLINE | ID: mdl-38952443

ABSTRACT

Introduction: Weeds are significant factors that detrimentally affect crop health and hinder optimal herbage yield. Rhizosphere microorganisms play crucial roles in plant growth, development, and nutrient uptake. Therefore, research focusing on weed control through the lens of microorganisms has emerged as a prominent area of study. The oil-producing fungus Mortierella, which is known for its numerous agricultural benefits, has garnered significant attention in recent years. Methods: In this study, we conducted inoculation experiments in a controlled artificial culture climate chamber to investigate the effects of differential hormones and differentially expressed genes in the stems and leaves of Digitaria sanguinalis using Liquid Chromatography Tandem Mass Spectrometry and RNA-seq techniques, respectively. Additionally, Pearson's correlation analysis was used to establish correlations between differential hormones and growth indicators of Digitaria sanguinalis. Results and discussion: The results demonstrated that inoculation with Mortierella sp. MXBP304 effectively suppressed aboveground biomass and plant height in Digitaria sanguinalis. Furthermore, there was significant upregulation and downregulation in the expression of genes involved in the synthesis and metabolism of phenylalanine and L-phenylalanine. Conversely, the expression of genes related to tryptophan, L-tryptophan, and indole was significantly downregulated. The addition of Mortierella sp. MXBP304 can influence the gene expression associated with phenylalanine and tryptophan synthesis and metabolism during Digitaria sanguinalis growth, subsequently reducing the relative contents of phenylalanine and tryptophan, thereby directly inhibiting Digitaria sanguinalis growth.

5.
Front Nutr ; 11: 1412031, 2024.
Article in English | MEDLINE | ID: mdl-38962437

ABSTRACT

Background: An antioxidant-rich diet has been shown to protect against migraines in previous research. However, little has been discovered regarding the association between migraines and vitamin C (an essential dietary antioxidant). This study assessed the dietary vitamin C intake among adult migraineurs in the United States to determine if there is a correlation between migraine incidence and vitamin C consumption in adults. Methods: This cross-sectional research encompassed adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, providing detailed information on their dietary vitamin C intake as well as their history of severe headaches or migraines. The study used weighted multivariable and logistic regression analyses to find an independent connection between vitamin C consumption and severe headache or migraine. Tests of interactions and subgroup analysis were conducted. Results: Among the 13,445 individuals in the sample, 20.42% had a severe headache or migraine. In fully adjusted models, dietary vitamin C consumption was substantially linked negatively with severe headache or migraine (odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.91-0.98, p = 0.0007). Compared to quartile 1, quartile 4 had 22% fewer odds of having a severe headache or migraine (OR = 0.78, 95% CI = 0.69-0.89, p = 0.0002). Subgroup analyses showed a significant difference between vitamin C intake and severe headaches or migraines by gender (p for interaction < 0.01). Conclusion: Reduced risk of severe headaches or migraines may be associated with increased consumption of vitamin C.

6.
Front Pediatr ; 12: 1361225, 2024.
Article in English | MEDLINE | ID: mdl-38962574

ABSTRACT

Pityriasis versicolor, a common skin fungal infection, is typically observed on trunk and limb skin. Here, we highlight an unusual presentation: scalp involvement, often overlooked due to its asymptomatic, mildly scaly patches. We report four pediatric cases, emphasizing the potential underestimation of this scalp variant. This case series underscores the importance of considering this diagnosis in patients with unexplained scalp hypopigmentation, especially in males with short hair who may readily notice these subtle changes. The report contributes to the understanding of this variant's clinical presentation and emphasizes the need for awareness among clinicians to ensure accurate diagnosis and appropriate management.

7.
Article in English | MEDLINE | ID: mdl-38970422

ABSTRACT

AIMS: Peroxiredoxin3 (Prdx3) is an intracellular antioxidant enzyme that is specifically localized in mitochondria and protects against oxidative stress by removing mitochondrial reactive oxygen species (ROS). The intestinal epithelium provides a physical and biochemical barrier that segregates host tissues from commensal bacteria to maintain intestinal homeostasis. An imbalance between the cellular antioxidant defense system and oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the role of Prdx3 in the intestinal epithelium under intestinal inflammation has not been elucidated. To investigate the potential role of Prdx3 in intestinal inflammation, we used intestinal epithelial cell (IEC)-specific Prdx3-knockout mice. RESULTS: IEC-specific Prdx3-deficient mice showed more severe colitis phenotypes with greater degrees of body weight loss, colon shortening, barrier disruption, mitochondrial damage, and ROS generation in IECs. Furthermore, exosomal miR-1260b was dramatically increased in Prdx3-knockdown colonic epithelial cells. Mechanistically, Prdx3 deficiency promoted intestinal barrier disruption and inflammation via P38-MAPK/NFκB signaling. INNOVATION: this is the first study to report the protective role of Prdx3 in acute colitis using IEC-specific conditional knockout mice. CONCLUSION: our study sheds light on the role of exosome-loaded miRNAs, particularly miR-1260b, in IBD. targeting miR-1260b or modulating exosome-mediated intercellular communication may hold promise as potential therapeutic strategies for managing IBD and restoring intestinal barrier integrity.

8.
J Gastrointest Surg ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986863

ABSTRACT

BACKGROUND: Esophageal variceal diameter (EVD) is one of the most important predictors of variceal bleeding, as well as an important predictor of the effectiveness of endoscopic esophageal varices (EV) treatments. EVD is currently determined using visual inspection by endoscopic operators, meaning that results can vary widely between operators. This approach also means that cases unsuitable for Endoscopic variceal ligation(EVL) can be complicated by postoperative hemorrhage. Thus, the purpose of this study was to explore the value of a virtual ruler (VR) in predicting rebleeding after the endoscopic treatment of EV in patients with cirrhosis. METHODS: We enrolled 588 patients with cirrhosis and EV (with and without gastric varices), who were treated with EVL or Endoscopic injection sclerotherapy (EIS) across three hospitals. We categorized participants into a non-bleeding group and a rebleeding group according to whether they bled again after surgery. We compared basic demographic and clinical data, laboratory tests, EVD, and treatment modalities between the two groups. Potential risk factors for rebleeding after EV operations were analyzed using univariate and multivariable regression analyses. Correlations between esophageal variceal rebleeding and EVD were also analyzed, as was consistency between visual EVD estimates and EVD measured using a VR. RESULTS: Child-Pugh class, Albumin (ALB)levels, Prothrombin Time (PT) levels, EVD (Visual value), EVD(VR value), red sign, and the number of laps used for EVL showed statistically significant differences between the rebleeding and non-bleeding groups. Univariate regression analysis showed that Child-Pugh classification, ALB levels, PT levels, EVD( VR value), and red sign were strongly associated with rebleeding after endoscopic treatment of EV, while multivariable regression analysis showed that Child-Pugh classification, ALB levels, and EVD (VR value) were predictive factors for rebleeding after endoscopic treatment of EV. Differences between visual EVD estimates and VR EVD measurements were large. (Kappa value: 0.391, p < 0.001). However, the two methods showed high agreement for EVD > 1cm (87/95) CONCLUSIONS: EVD (VR value) can more accurately predict rebleeding rates. It can also provide a basis for selecting appropriate endoscopic treatment modalities for EV and effectively circumvent postoperative EV rebleeding.

9.
Imeta ; 3(3): e199, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38898986

ABSTRACT

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.

10.
Article in English | MEDLINE | ID: mdl-38906043

ABSTRACT

The intestine is an important organ for food digestion and absorption and body immunity in fish. In this study, we investigated the abundance of transcripts from different segments of the intestinal tract using transcriptome sequencing technology in Hemibarbus labeo, to provide functional insights into digestion, absorption, and immunity in the anterior intestine (AI), middle intestine (MI), and posterior intestine (PI). We found 5646 differentially expressed genes (DEGs), which were significantly enriched to GO terms of carbohydrate metabolic process, transmembrane transport, iron ion binding, lipid metabolic process, and KEGG pathway of fat digestion and absorption, mineral absorption, protein digestion and absorption, vitamin digestion and absorption, indicating that the digestion and absorption function of food is different in AI, MI, and PI. In practice, most genes, enriched in the KEGG pathway for digestion and absorption of nutrients, are upregulated in AI and MI, indicating stronger roles for food digestion and absorption in these segments. Furthermore, we found that genes involved in the KEGG pathway of lysosome and endocytosis pathway are upregulated in PI, suggesting stronger antigen-presenting capabilities in PI. However, some cytokine receptor genes, including ccr4, cxcr2, tnfrsf9, il6r, csf3r, and cxcr4, are highly expressed in AI, reflecting the regional immune specialization in different segments. This study provides functional insights into digestion, absorption, and immunity in different segments of the intestine and supports the regional functional specialization within different segments of the intestine in H. labeo.

11.
J Chromatogr A ; 1730: 465097, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38889583

ABSTRACT

Magnetic surface imprinted polymer microspheres (Fe3O4@MIPs) were successfully synthesized via Pickering emulsion polymerization, utilizing N-Methylphenethylamine as a surrogate template for amphetamine-type drugs. Fe3O4@MIPs not only possessed excellent dispersibility and enough magnetic properties in aqueous solutions, but also displayed good selectivity towards six amphetamines, with an imprinting factor ranging from 1.8 to 2.6. The adsorption kinetics closely aligned with the pseudo-second-order model, and the adsorption efficiency exceeds 80 % for each amphetamine at equilibrium. Fe3O4@MIPs were then employed as the efficient adsorbents for the extraction of amphetamine drugs. Extraction parameters, including sample pH, the mass of adsorbent, and the type and volume of eluting solvent, were carefully optimized. In combination with the high performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS), a selective magnetic solid-phase extraction (MISPE) method utilizing Fe3O4@MIPs was developed for the detection of six amphetamines in water samples. The limits of detection and limits of quantitation were determined to be 5.2∼23 ng L-1 and 17∼77 ng L-1, respectively. Recoveries for the six target drugs from lake water and sewage samples fell within the range of 87.2∼110 %. Additionally, the MISPE-HPLC-MS/MS method exhibited excellent repeatability, with a precision below 8.5 % at two spiking levels. The prepared Fe3O4@MIPs possessed the advantages of high selectivity, straightforward preparation, facile separation and good reusability, and was highly suitable for the efficient extraction of amphetamine-type substances in complex environmental water.

12.
Reprod Toxicol ; 128: 108644, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880404

ABSTRACT

Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.

13.
J Dairy Sci ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945261

ABSTRACT

Despite considerable research efforts, lipase catalysis in a fluid milk system with aqueous multi-component mixtures containing multiple microphases, remains challenging. Pickering interfacial biocatalysis (PIB) platforms are typically fabricated with organic solvents/lipids and water. Whether a PIB with excellent catalytic performance can be constructed in complex milk mixtures remains unknown. Here, we challenged PIB with skim milk, and a small amount of flaxseed oil, and phytosterols as a model system for transesterification and lipolysis to enhance quality and flavor. The amino-modified mesoporous silica spheres (MSS-N) were employed as an emulsifier and carrier of lipase AYS (AYS@MSS-N). The conversion of phytosterol esters reached 75.5% at 1.5 h and prepared phytosterol ester-fortified milk with a content of 1.0 g/100 mL. The relative conversion rate remained above 70% after 6 cycles. In addition, the fortified milk showed an intensified and favorable effect on sensory traits through volatile flavor composition analysis. The findings provide a versatile alternative for PIB applications in complex environments, i.e., milk, which might inspire a new bioprocess strategy for dairy products.

14.
Neural Netw ; 178: 106470, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38943861

ABSTRACT

Brain-computer interfaces (BCIs) built based on motor imagery paradigm have found extensive utilization in motor rehabilitation and the control of assistive applications. However, traditional MI-BCI systems often exhibit suboptimal classification performance and require significant time for new users to collect subject-specific training data. This limitation diminishes the user-friendliness of BCIs and presents significant challenges in developing effective subject-independent models. In response to these challenges, we propose a novel subject-independent framework for learning temporal dependency for motor imagery BCIs by Contrastive Learning and Self-attention (CLS). In CLS model, we incorporate self-attention mechanism and supervised contrastive learning into a deep neural network to extract important information from electroencephalography (EEG) signals as features. We evaluate the CLS model using two large public datasets encompassing numerous subjects in a subject-independent experiment condition. The results demonstrate that CLS outperforms six baseline algorithms, achieving a mean classification accuracy improvement of 1.3 % and 4.71 % than the best algorithm on the Giga dataset and OpenBMI dataset, respectively. Our findings demonstrate that CLS can effectively learn invariant discriminative features from training data obtained from non-target subjects, thus showcasing its potential for building models for new users without the need for calibration.

15.
Nat Commun ; 15(1): 4857, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849365

ABSTRACT

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.


Subject(s)
Antibodies, Monoclonal , Antibodies, Protozoan , Antigens, Protozoan , Malaria Vaccines , Malaria, Falciparum , Plasmodium falciparum , Protozoan Proteins , Malaria Vaccines/immunology , Malaria Vaccines/administration & dosage , Animals , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Female , Malaria, Falciparum/prevention & control , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Antigens, Protozoan/immunology , Rats , Antibodies, Protozoan/immunology , Antibodies, Monoclonal/immunology , Humans , Epitopes/immunology , Carrier Proteins/immunology , Carrier Proteins/metabolism
16.
J Neural Eng ; 21(4)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38848710

ABSTRACT

Objective.Event-related potentials (ERPs) are cerebral responses to cognitive processes, also referred to as cognitive potentials. Accurately decoding ERPs can help to advance research on brain-computer interfaces (BCIs). The spatial pattern of ERP varies with time. In recent years, convolutional neural networks (CNNs) have shown promising results in electroencephalography (EEG) classification, specifically for ERP-based BCIs.Approach.This study proposes an auto-segmented multi-time window dual-scale neural network (AWDSNet). The combination of a multi-window design and a lightweight base network gives AWDSNet good performance at an acceptable cost of computing. For each individual, we create a time window set by calculating the correlation of signedR-squared values, which enables us to determine the length and number of windows automatically. The signal data are segmented based on the obtained window sets in sub-plus-global mode. Then, the multi-window data are fed into a dual-scale CNN model, where the sizes of the convolution kernels are determined by the window sizes. The use of dual-scale spatiotemporal convolution focuses on feature details while also having a large enough receptive length, and the grouping parallelism undermines the increase in the number of parameters that come with dual scaling.Main results.We evaluated the performance of AWDSNet on a public dataset and a self-collected dataset. A comparison was made with four popular methods including EEGNet, DeepConvNet, EEG-Inception, and PPNN. The experimental results show that AWDSNet has excellent classification performance with acceptable computational complexity.Significance.These results indicate that AWDSNet has great potential for applications in ERP decoding.


Subject(s)
Brain-Computer Interfaces , Electroencephalography , Evoked Potentials , Neural Networks, Computer , Humans , Electroencephalography/methods , Evoked Potentials/physiology , Male , Adult , Female , Young Adult , Time Factors
17.
J Am Chem Soc ; 146(26): 17747-17756, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38889317

ABSTRACT

Unveiling molecular mechanisms that dominate protein phase dynamics has been a pressing need for deciphering the intricate intracellular modulation machinery. While ions and biomacromolecules have been widely recognized for modulating protein phase separations, effects of small molecules that essentially constitute the cytosolic chemical atmosphere on the protein phase behaviors are rarely understood. Herein, we report that vitamin C (VC), a key small molecule for maintaining a reductive intracellular atmosphere, drives reentrant phase transitions of myosin II/F-actin (actomyosin) cytoskeletons. The actomyosin bundle condensates dissemble in the low-VC regime and assemble in the high-VC regime in vitro or inside neuronal cells, through a concurrent myosin II protein aggregation-dissociation process with monotonic VC concentration increase. Based on this finding, we employ in situ single-cell and single-vesicle electrochemistry to demonstrate the quantitative modulation of catecholamine transmitter vesicle exocytosis by intracellular VC atmosphere, i.e., exocytotic release amount increases in the low-VC regime and decreases in the high-VC regime. Furthermore, we show how VC regulates cytomembrane-vesicle fusion pore dynamics through counteractive or synergistic effects of actomyosin phase transitions and the intracellular free calcium level on membrane tensions. Our work uncovers the small molecule-based reversive protein phase regulatory mechanism, paving a new way to chemical neuromodulation and therapeutic repertoire expansion.


Subject(s)
Actins , Ascorbic Acid , Exocytosis , Ascorbic Acid/chemistry , Ascorbic Acid/pharmacology , Exocytosis/drug effects , Actins/metabolism , Actins/chemistry , Phase Transition , Animals , Myosin Type II/metabolism , Myosin Type II/antagonists & inhibitors , Electrochemical Techniques , Actomyosin/metabolism , Actomyosin/chemistry , Rats
18.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860546

ABSTRACT

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

19.
J Forensic Sci ; 69(4): 1429-1440, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880998

ABSTRACT

To establish the correlation between thermal conditions imposed on bloodstains and visualizing effect of enhancement techniques, infrared photography and four chemical enhancement reagents were used to visualize bloodstains following thermal exposure. A black tile was selected as the substrate to intensify the visualization challenge, with a Cone Calorimeter serving as the standardized heating source to control thermal conditions. Compared with standard photography, infrared photography is proven to be a valuable complement to chemical reagents, showing significant advantages in visualizing bloodstains after thermal exposure. However, it is worth noting that infrared image fell short of standard image when bloodstains displayed raised, embossed morphology or when bloodstains almost disappeared under specific conditions. The enhancement effectiveness was found to be strongly correlated with thermal conditions imposed on bloodstains, and the morphology evolution of bloodstains during heating affected the chemical enhancement effect additionally, especially when the bulge morphology was formed, and it was observed that reagents were more effective after removing the dense shell of the bulge. Among the four selected chemical enhancement reagents, fluorescein performed exceptionally well, maintaining its effectiveness even for bloodstains heated at 641°C for 10 min. TMB demonstrated its visualizing ability for bloodstains heated at 396°C for 5 min and heated at 310°C for 20 min. BLUESTAR® followed afterwards, while luminol performed worst. The correlation between thermal conditions imposed on bloodstains and the corresponding visualizing effectiveness of enhancement techniques provides important references for detecting bloodstains at fire scenes.


Subject(s)
Blood Stains , Hot Temperature , Photography , Humans , Infrared Rays , Luminol , Fluorescein , Indicators and Reagents , Calorimetry , Fluorescent Dyes , Forensic Medicine/methods , Luminescent Agents
20.
J Neural Eng ; 21(3)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38885683

ABSTRACT

Objective. In brain-computer interfaces (BCIs) that utilize motor imagery (MI), minimizing calibration time has become increasingly critical for real-world applications. Recently, transfer learning (TL) has been shown to effectively reduce the calibration time in MI-BCIs. However, variations in data distribution among subjects can significantly influence the performance of TL in MI-BCIs.Approach.We propose a cross-dataset adaptive domain selection transfer learning framework that integrates domain selection, data alignment, and an enhanced common spatial pattern (CSP) algorithm. Our approach uses a huge dataset of 109 subjects as the source domain. We begin by identifying non-BCI illiterate subjects from this huge dataset, then determine the source domain subjects most closely aligned with the target subjects using maximum mean discrepancy. After undergoing Euclidean alignment processing, features are extracted by multiple composite CSP. The final classification is carried out using the support vector machine.Main results.Our findings indicate that the proposed technique outperforms existing methods, achieving classification accuracies of 75.05% and 76.82% in two cross-dataset experiments, respectively.Significance.By reducing the need for extensive training data, yet maintaining high accuracy, our method optimizes the practical implementation of MI-BCIs.


Subject(s)
Brain-Computer Interfaces , Imagination , Transfer, Psychology , Humans , Imagination/physiology , Transfer, Psychology/physiology , Support Vector Machine , Electroencephalography/methods , Movement/physiology , Algorithms , Machine Learning , Databases, Factual , Male
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