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1.
Med Biol Eng Comput ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724769

ABSTRACT

Motor imagery (MI) based brain-computer interfaces (BCIs) decode the users' intentions from electroencephalography (EEG) to achieve information control and interaction between the brain and external devices. In this paper, firstly, we apply Riemannian geometry to the covariance matrix extracted by spatial filtering to obtain robust and distinct features. Then, a multiscale temporal-spectral segmentation scheme is developed to enrich the feature dimensionality. In order to determine the optimal feature configurations, we utilize a linear learning-based temporal window and spectral band (TWSB) selection method to evaluate the feature contributions, which efficiently reduces the redundant features and improves the decoding efficiency without excessive loss of accuracy. Finally, support vector machines are used to predict the classification labels based on the selected MI features. To evaluate the performance of our model, we test it on the publicly available BCI Competition IV dataset 2a and 2b. The results show that the method has an average accuracy of 79.1% and 83.1%, which outperforms other existing methods. Using TWSB feature selection instead of selecting all features improves the accuracy by up to about 6%. Moreover, the TWSB selection method can effectively reduce the computational burden. We believe that the framework reveals more interpretable feature information of motor imagery EEG signals, provides neural responses discriminative with high accuracy, and facilitates the performance of real-time MI-BCI.

2.
Ecotoxicol Environ Saf ; 279: 116497, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38805827

ABSTRACT

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

3.
3 Biotech ; 14(4): 103, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38464614

ABSTRACT

To elucidate the mechanisms governing the salt tolerance of the endangered semi-mangrove plant Barringtonia racemosa, the biomass, photosynthetic and fluorescent characteristics, and anatomical structure of B. racemosa were studied under low, medium and high salt stress. The results showed that the stem dry weight, net photosynthetic rate, intercellular CO2 concentration, Fv/Fm, and ΦPSI of B. racemosa decreased under high salt stress, which led to a significant reduction in total dry weight. Stem dry weight was significantly positively correlated with the thickness of palisade tissue and significantly negatively correlated with the thickness of the epidermis of roots and xylem of stems. Therefore, a stable net photosynthetic rate and intercellular CO2 concentration, an increase in Fv/Fm and ΦPSI, an increase in or stable palisade tissue and spongy mesophyll of leaves and an increase in xylem thickness of the stem and epidermis, outer cortex, and stele diameter of roots could contribute to the salt tolerance of B. racemosa.

4.
Urol Int ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38513631

ABSTRACT

INTRODUCTION: To present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253±51.4 min and 238.9±196.9 ml, with a mean postoperative follow-up time of 13.0±5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (P=0.006 and P=0.024). The postoperative 3-month and 1-year eGFR values were significantly increased comapred with those before operation (P=0.0002 and P=0.018). The separation value of left renal pelvis collection system after operation were significantly reduced compared with preoperative evaluation (P=0.023 at 3 month and P=0.042 at 1 year) and so was the right side (P=0.019 and P=0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

5.
Cardiovasc Pathol ; 70: 107630, 2024.
Article in English | MEDLINE | ID: mdl-38490313

ABSTRACT

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases.


Subject(s)
Carnitine Acyltransferases , Lipid Metabolism, Inborn Errors , Mutation , Humans , Infant, Newborn , Female , Carnitine Acyltransferases/deficiency , Carnitine Acyltransferases/genetics , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/pathology , Lipid Metabolism, Inborn Errors/complications , Lipid Metabolism, Inborn Errors/diagnosis , Phenotype , Fatal Outcome , Genetic Predisposition to Disease , Sudden Infant Death/genetics , Sudden Infant Death/pathology , Sudden Infant Death/etiology , Autopsy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/pathology , Cause of Death , Carnitine/analogs & derivatives , Carnitine/deficiency , Mitochondrial Membrane Transport Proteins/genetics , Myocardium/pathology , Myocardium/metabolism , Membrane Transport Proteins
6.
Chronobiol Int ; 41(2): 267-282, 2024 02.
Article in English | MEDLINE | ID: mdl-38267234

ABSTRACT

In modern 24-hour society, various round-the-clock services have entailed shift work, resulting in non-24-hour schedules. However, the extent of behavioral and physiological alterations by non-24-hour schedules remains unclear, and particularly, effective interventions to restore the circadian functions of non-24-hour shift workers are rarely explored. In this study, we investigate the effects of a simulated non-24-hour military shift work schedule on daily rhythms and sleep, and establish an intervention measure to restore the circadian functions of non-24-hour shift workers. The three stages of experiments were conducted. The stage-one experiment was to establish a comprehensive evaluation index of the circadian rhythms and sleep for all 60 participants by analyzing wristwatch-recorded physiological parameters and sleep. The stage-two experiment evaluated the effects of an intervention strategy on physiological rhythms and sleep. The stage-three experiment was to examine the participants' physiological and behavioral disturbances under the simulated non-24-hour military shift work schedule and their improvements by the optimal lighting apparatus. We found that wristwatch-recorded physiological parameters display robust rhythmicity, and the phases of systolic blood pressures and heart rates can be used as reliable estimators for the human body time. The simulated non-24-hour military shift work schedule significantly disrupts the daily rhythms of oxygen saturation levels, blood pressures, heart rates, and reduces sleep quality. Administration of blue light in the morning and no blue-ray light in the evening improves the amplitude and synchronization of daily rhythms of the non-24-hour participants. These findings demonstrate the harmful consequences of the non-24-hour shift work schedule and provide a non-invasive strategy to improve the well-being and work efficiency of the non-24-hour shift population.


Subject(s)
Circadian Rhythm , Melatonin , Humans , Circadian Rhythm/physiology , Blue Light , Light , Sleep/physiology , Work Schedule Tolerance/physiology
7.
Nurs Open ; 11(1): e2096, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38268282

ABSTRACT

AIM: Moral courage among healthcare workers has been extensively studied. However, few studies have been conducted on oncology specialist nurses, who frequently encounter complex moral situations. This study aimed to describe the current situation regarding moral courage and explored its influence on oncology specialist nurses in China. DESIGN: This was an exploratory, descriptive study. METHODS: A convenience sample of 390 nurses was conducted from 15 hospitals in Sichuan Province, China, between March and May 2023. Participants were assessed using the Moral Distress Scale-Revised, Nurses' Moral Courage Scale and the Moral Sensitivity Questionnaire. RESULTS: The results demonstrated that moral courage was negatively associated with moral distress, and positively associated with moral sensitivity. Having a master's degree or above, an intermediate title or senior title, medical ethics training, moral distress or moral sensitivity contributed to explaining 54.1% of the variance in moral courage. CONCLUSIONS: Moral courage was associated with several factors. Developing clinical intervention strategies and effective teaching methods will be critical for improving moral courage. No Patient or Public Contribution.


Subject(s)
Courage , Humans , Cross-Sectional Studies , Morals , Research Design , China
8.
Front Pharmacol ; 14: 1246761, 2023.
Article in English | MEDLINE | ID: mdl-38035004

ABSTRACT

The importance of adequate sleep for good health cannot be overstated. Excessive light exposure at night disrupts sleep, therefore, it is important to find more healthy drinks that can promote sleep under sleep-disturbed conditions. The present study investigated the use of A. sinensis (Lour.) Spreng leaf tea, a natural product, to reduce the adverse effects of nighttime light on sleep. Here, Aquilaria sinensis leaf tea at 1.0 and 1.5 g/L significantly increased sleep time in zebrafish larvae (5-7 dpf) with light-induced sleep disturbance. Transcriptome sequencing and qRT-PCR analysis revealed a decrease in the immune-related genes, such as nfkbiab, tnfrsf1a, nfkbiaa, il1b, traf3, and cd40 in the 1.5 g/L Aquilaria sinensis leaf tea treatment group. In addition, a gene associated with sleep, bhlhe41, showed a significant decrease. Moreover, Aquilaria sinensis leaf tea suppressed the increase in neutrophils of Tg(mpo:GFP) zebrafish under sleep-disturbed conditions, indicating its ability to improve the immune response. Widely targeted metabolic profiling of the Aquilaria sinensis tea using ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) revealed flavonoids as the predominant component. Network pharmacological and molecular docking analyses suggested that the flavonoids quercetin and eupatilin in Aquilaria sinensis leaf tea improved the sleep of zebrafish by interacting with il1b and cd40 genes under light exposure at night. Therefore, the results of the study provide evidence supporting the notion that Aquilaria sinensis leaf tea has a positive impact on sleep patterns in zebrafish subjected to disrupted sleep due to nighttime light exposure. This suggests that the utilization of Aquilaria sinensis leaf tea as a potential therapeutic intervention for sleep disturbances induced by light may yield advantageous outcomes.

9.
Int J Biol Sci ; 19(13): 4004-4019, 2023.
Article in English | MEDLINE | ID: mdl-37705751

ABSTRACT

Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of the G-protein-coupled receptor (APJ), is abundantly expressed in diverse organs. The apelin-APJ axis helps to control pathological and physiological processes in lung. The role of apelin in the pathological process and its possible therapeutic effects on silicosis have not been elucidated. In this study, we found that lung expression and circulating levels of apelin were markedly decreased in silicosis patients and silica-induced fibrotic mice and associated with the severity. Furthermore, in vivo data demonstrated that pre-treatment from day 3 and post-treatment from day 15 with apelin could both alleviate silica-induced pulmonary fibrosis in mice. Besides, apelin inhibited pulmonary fibroblast activation via transforming growth factor beta 1 (TGF-ß1) signaling. Our study suggested that apelin could prevent and reverse silica-induced pulmonary fibrosis by inhibiting the fibroblast activation through TGF-ß1 signaling pathway, thus providing a new potential therapeutic strategy for silicosis and other pulmonary fibrosis.


Subject(s)
Pulmonary Fibrosis , Silicosis , Animals , Mice , Apelin , Fibroblasts , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Silicon Dioxide/toxicity , Silicosis/drug therapy , Transforming Growth Factor beta1
10.
Chemosphere ; 339: 139650, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37495056

ABSTRACT

Air sparging (AS) is deemed unacceptable for remediating VOCs contaminated soil with low-permeability. To improve air flow and contaminant removal in sparging process, an original approach, termed as pressure gradient-enhanced air sparging (PGEAS) approach, is proposed by controlling pressure gradient in soil. Then the remediation efficiency, mass transfer characteristics, and remediation mechanism are investigated. Results showed that, the PGEAS approach accelerates gaseous contaminant exhaust, reduces residue contamination in soil, and promotes total contaminant removal, finally results in an improved remediation efficiency compared to the conventional approach. Controlled by sparging pressure and flow distance, the pressure gradient is created in soil, and a critical value needs to be exceeded to enhance the VOCs removal and mass transfer characteristics. The measured results of pore pressure and liquid saturation confirm a notable pressure gradient and drainage behavior in soil, which indicate the massive air subchannel formation during air sparging. At a two-dimensional scale, discrete distributions of contaminant concentrations in exhaust air and soil are presented, the removal extent and area are both enhanced using the PGEAS approach with a pressure gradient higher than the critical value. The reached conclusions are of great importance to contaminant removal in heterogeneous stratigraphy at sites.


Subject(s)
Environmental Restoration and Remediation , Soil Pollutants , Soil/chemistry , Air , Gases , Chemical Phenomena , Permeability , Soil Pollutants/analysis
11.
Materials (Basel) ; 16(9)2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37176327

ABSTRACT

In the past few decades, solidification/stabilization (S/S) technology has been put forward for the purpose of improving soil strength and inhibiting contaminant migration in the remediation of heavy metal-contaminated sites. Cement, lime, and fly ash are among the most common and effective binders to treat contaminated soils. During S/S processing, the main interactions that are responsible for improving the soil's behaviors can be summarized as gelification, self-hardening, and aggregation. Currently, precipitation, incorporation, and substitution have been commonly accepted as the predominant immobilization mechanisms for heavy metal ions and have been directly verified by some micro-testing techniques. While replacement of Ca2+/Si4+ in the cementitious products and physical encapsulation remain controversial, which is proposed dependent on the indirect results. Lead and zinc can retard both the initial and final setting times of cement hydration, while chromium can accelerate the initial cement hydration. Though cadmium can shorten the initial setting time, further cement hydration will be inhibited. While for mercury, the interference impact is closely associated with its adapted anion. It should be pointed out that obtaining a better understanding of the remediation mechanism involved in S/S processing will contribute to facilitating technical improvement, further extension, and application.

12.
J Cancer ; 14(4): 573-590, 2023.
Article in English | MEDLINE | ID: mdl-37057291

ABSTRACT

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.

13.
Sex Med ; 11(1): qfac008, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37056514

ABSTRACT

Background: Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood. Aim: We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis. Methods: Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe2+), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins. Outcomes: At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe2+, and ROS. Results: PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe2+, MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death. Clinical Translation: This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction. Strengths and Limitations: In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed. Conclusion: Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study.

14.
Forensic Sci Int ; 345: 111619, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36870177

ABSTRACT

BACKGROUND: Death from nontraumatic pulmonary fat embolism associated with minor soft tissue contusion, surgery, cancer chemotherapy, hematologic disorders and so on has been reported. Patients often present with atypical manifestations and rapid deterioration, making diagnosis and treatment difficult. However, there are no reported cases of death from pulmonary fat embolism after acupuncture therapy. This case emphasizes that the stress induced by acupuncture therapy, a mild soft tissue injury, plays an important role in pulmonary fat embolism. In addition, it suggests that in such cases, pulmonary fat embolism as a complication of acupuncture therapy needs to be taken seriously, and autopsy should be used to identify the source of fat emboli. CASE PRESENTATION: The patient was 72 years old female and experienced dizziness and fatigue after silver-needle acupuncture therapy. She experienced a significant drop in blood pressure and died 2 h later despite treatment and resuscitation. A systemic autopsy and histopathology examination (H&E and Sudan Ⅲ staining) were performed. More than 30 pinholes were observed in the lower back skin. Focal hemorrhages were seen surrounding the pinholes in the subcutaneous fatty tissue. Microscopically, numerous fat emboli were observed in the interstitial pulmonary arteries and alveolar wall capillaries, in addition to the vessels of the heart, liver, spleen and thyroid gland. The lungs showed congestion and edema. The cause of death was identified as pulmonary fat embolism. CONCLUSION: This article suggests that high vigilance for risk factors and the complication of pulmonary fat embolism following silver-needle acupuncture therapy should be exercised. In postmortem examinations, it should be pay attention that the peripheral arterial system and the venous system draining from non-injured sites should be examined for the formation of fat emboli, which can help distinguish posttraumatic and nontraumatic pulmonary fat embolism.


Subject(s)
Acupuncture Therapy , Embolism, Fat , Pulmonary Embolism , Humans , Female , Aged , Silver , Pulmonary Embolism/complications , Lung/pathology , Embolism, Fat/etiology , Embolism, Fat/diagnosis , Embolism, Fat/pathology , Acupuncture Therapy/adverse effects
15.
Article in English | MEDLINE | ID: mdl-36232247

ABSTRACT

Mangrove plants play an important role in the remediation of heavy-metal-contaminated estuarine and coastal areas; Barringtonia racemosa is a typical semi-mangrove plant. However, the effect of heavy metal stress on this plant has not been explored. In this study, tolerance characteristics and the accumulation profile of cadmium (Cd) and lead (Pb) in B. racemosa were evaluated. The results indicated that B. racemosa exhibited a high tolerance in single Cd/Pb and Cd + Pb stress, with a significant increase in biomass yield in all treatment groups, a significant increase in plant height, leaf area, chlorophyll and carotenoid content in most treatment groups and without significant reduction of SOD, POD, MDA, proline content, Chl a, Chl b, Chl a + b, Car, ratio of Chl a:b and ratio of Car:Chl (a + b). Cd and Pb mainly accumulated in the root (≥93.43%) and the content of Cd and Pb in B. racemosa was root > stem > leaf. Pb showed antagonistic effects on the Cd accumulation in the roots and Cd showed antagonistic or synergistic effects on the Pb accumulation in the roots, which depended on the concentration of Cd and Pb. There was a significant synergistic effect of Cd and Pb enrichment under a low Cd and Pb concentration treatment. Thus, phytoremediation could potentially use B. racemosa for Cd and Pb.


Subject(s)
Barringtonia , Metals, Heavy , Soil Pollutants , Biodegradation, Environmental , Cadmium/analysis , Carotenoids , Chlorophyll , Lead , Plant Roots/chemistry , Proline , Soil , Soil Pollutants/analysis , Superoxide Dismutase
16.
PeerJ ; 10: e14192, 2022.
Article in English | MEDLINE | ID: mdl-36312762

ABSTRACT

Icariside II, as a favonoid compound derived from epimedium, has been proved to involed in a variety of biological and pharmacological effects such as anti-inflammatory, anti-osteoporosis, anti-oxidation, anti-aging, and anti-cancer but its mechanism is unclear, especially in terms of its effect on post-transcriptional modification of endothelial nitric oxide synthase (eNOS). Phosphorylation of eNOS plays an important role in the synthesis of nitric oxide in endothelial cells, which is closely related to erectile dysfunction, atherosclerosis, Alzheimer's disease, and other diseases. Our study aims to investigate the effect and mechanism of Icariside II on the rapid phosphorylation of eNOS. In this study, human umbilical vein endothelial cells (HUVECs) were stimulated with Icariside II in the presence or absence of multiple inhibitors (1 µM), including LY294002 (PI3K-inhibitor), MK-2206 (AKT-inhibitor), Bisindolylmaleimide X (AMPK-inhibitor), H-89 (CaMKII-inhibitor), KN-62 (PKA-inhibitor), Dorsomorphin (PKC-inhibitor). The proliferation of HUVECs was assessed using cell counting kit-8 (CCK-8). The release of nitric oxide (NO) within HUVECs was detected via fluorescence probe (DAF-FM). Western blot was used to examine the effect of Icariside II on the expression of eNOS, phosphorylation of eNOS, and common signaling pathways proteins. In this study, Icariside II was found to promote the cell proliferation and rapid NO release in HUVECs. The phosphorylation of eNOS-Ser1177 was significantly increased after Icariside II stimulation and reached a peak at 10 min (p < 0.05). Meanwhile, the phosphorylation of eNOS-Thr495 was significantly decreased after 45 min of stimulation (p < 0.05). Following the intervention with multiple inhibitors, it was found that MK-2206 (AKT inhibitor), LY294002 (PI3K inhibitor), KN-62 (AMPK inhibitor), and Bisindolylmaleimide X (PKC inhibitor) could significantly inhibit the phosphorylation of eNOS-Ser1177 caused by Icariside II (p < 0.05), while MK-2206, LY294002, and Bisindolylmaleimide X reversed the alleviated phosphorylation of eNOS-Thr495. We concluded that Icariside can regulate rapid phosphorylation of eNOS- Ser1177 and eNOS-Thr495 via multiple signaling pathways, resulting in the up-regulation of eNOS and the increased release of NO.


Subject(s)
Nitric Oxide Synthase Type III , Proto-Oncogene Proteins c-akt , Male , Humans , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Nitric Oxide/metabolism , AMP-Activated Protein Kinases/metabolism , Signal Transduction , Human Umbilical Vein Endothelial Cells
17.
Front Pharmacol ; 13: 920601, 2022.
Article in English | MEDLINE | ID: mdl-35846993

ABSTRACT

Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction. Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay. Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway. Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway.

18.
J Contam Hydrol ; 250: 104049, 2022 10.
Article in English | MEDLINE | ID: mdl-35863213

ABSTRACT

Surfactant-enhanced air sparging (SEAS) is an effective technology for the remediation of volatile organic compounds contamination of medium and high-permeability soil, though applying SEAS to low-permeability soil contamination has rarely been explored. In this study, a series of two-dimensional physical model tests were designed to explore the feasibility and remediation characteristics of SEAS on low-permeability soil. In the test results, the incorporation and increase in surfactant concentration promoted air channel formation in the low-permeability soil, finally reduced the capillary breakthrough pressure and improved the airflow rate. The majority of the exhausted gaseous contaminants were distributed along the horizontal direction, differing from the results observed in medium and high-permeability soils. The exhausted gaseous contaminant concentration changed slightly when the sparging pressure and surfactant concentration increased at relatively low levels and increased as the sparging pressure and surfactant concentration increased further. Increasing the air sparging pressure without surfactant incorporation or with a low surfactant concentration cannot effectively remove the contaminant, while the removal efficiency can be enhanced with further increases in surfactant concentration. The discrete remediation characteristics had been confirmed during SEAS application on low-permeability soil, then the relationships between the ratios of remediation area and remediation extent under different surfactant concentrations and sparging pressures were established for remediation efficiency evaluation. Using this method, the discrete remediation characteristics can be recreated once the surfactant concentration and the sparging pressure were chosen. On the other side, targeted improvements in the remediation area or extent can be achieved by controlling the surfactant concentration and sparging pressure. Through this study, SEAS technology and the proposed evaluation method were successfully implemented in soil with hydraulic conductivity around 9E-7 m/s, which expanded the application scope of SEAS technology for contaminant removal.


Subject(s)
Environmental Restoration and Remediation , Soil Pollutants , Volatile Organic Compounds , Oceans and Seas , Permeability , Soil , Soil Pollutants/analysis , Surface-Active Agents , Technology
19.
Front Endocrinol (Lausanne) ; 13: 874915, 2022.
Article in English | MEDLINE | ID: mdl-35518933

ABSTRACT

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level. Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB. Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED. Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.


Subject(s)
Erectile Dysfunction , Endothelial Cells , Erectile Dysfunction/genetics , Erectile Dysfunction/pathology , Humans , Male , Penile Erection/physiology , Penis/pathology , Sequence Analysis, RNA
20.
Forensic Sci Int Genet ; 59: 102705, 2022 07.
Article in English | MEDLINE | ID: mdl-35462161

ABSTRACT

BACKGROUNDS: Y-chromosomal haplotypes based on Y-short tandem repeats (STRs) and Y-single nucleotide polymorphisms/insertion and deletion polymorphisms (SNPs/InDels) are used to characterize paternal lineages of unknown male trace donors. However, Y-chromosomal genetic markers are not currently sufficient for precise individual identification. Microhaplotype (MH), generally < 200 bp on autosomes and consisting of two or more SNPs, was recently introduced in forensic genetics with the development of massive parallel sequencing technology and may facilitate identification and DNA mixture deconvolution. Therefore, combining the two kinds of genetic markers may be beneficial in many forensic scenarios, especially crime scenes with male suspects, such as sexual assault cases. METHODS: In the present study, we developed a novel MPS-based panel, Microhaplotype and Y-SNP/STR (MY), by multiplex PCR and 150-bp paired-end sequencing, including 114 Y-SNPs (twelve dominant Y-DNA haplogroups), 45 Y-STRs (N-1 stutter < 0.09; estimated mutation rate < 5 × 10-3), and 22 MHs (allele coverage ratio > 0.91; pairwise distance > 10 Mb). Additionally, MY system-based genotype pattern recognition (GPR), a regression-based method to identify the genotype pattern for each MH locus, is proposed for two-person DNA mixture deconvolution. We integrated 26 two-person genotype combinations into nine genotype patterns and validated the application range of GPR based on DNA profiles of ten sets of simulated male-male DNA mixtures (1:10-1:2). RESULTS: The effective number of alleles (Ae) ranged from 3.62 to 14.72, with an average of 7.17, in 100 Chinese Guangdong Han individuals. The cumulative discrimination power was 1-5.00 × 10-31, and the cumulative power of exclusion was 1-5.00 × 10-8 and 1-4.85 × 10-12 for duo and trio paternity testing, respectively. Furthermore, the actual mixing ratio-depth of coverage (DoC) ratio (RDoC) regression relationships were established for different genetic markers and genotype patterns. In five overlapping areas, genotype differentiation of the major and minor contributors required likelihood ratio methods. In nonoverlapping areas, the genotype pattern could be recognized by comparing the observed RDoC and RDoC ranges. CONCLUSION: The GPR can be used to deconvolute two-person DNA mixtures (application range: 1:10-1:2) for individual identification.


Subject(s)
DNA Fingerprinting , Polymorphism, Single Nucleotide , DNA/analysis , DNA/genetics , DNA Fingerprinting/methods , Genetic Markers , Genotype , Haplotypes , High-Throughput Nucleotide Sequencing , Humans , Male , Microsatellite Repeats
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