ABSTRACT
Spermatogonial stem cells (SSCs) undergo self-renewal division to sustain spermatogenesis. Although it is possible to derive SSC cultures in most mouse strains, SSCs from a 129 background never proliferate under the same culture conditions, suggesting they have distinct self-renewal requirements. Here, we established long-term culture conditions for SSCs from mice of the 129 background (129 mice). An analysis of 129 testes showed significant reduction of GDNF and CXCL12, whereas FGF2, INHBA and INHBB were higher than in testes of C57BL/6 mice. An analysis of undifferentiated spermatogonia in 129 mice showed higher expression of Chrna4, which encodes an acetylcholine (Ach) receptor component. By supplementing medium with INHBA and Ach, SSC cultures were derived from 129 mice. Following lentivirus transduction for marking donor cells, transplanted cells re-initiated spermatogenesis in infertile mouse testes and produced transgenic offspring. These results suggest that the requirements of SSC self-renewal in mice are diverse, which has important implications for understanding self-renewal mechanisms in various animal species.
Subject(s)
Mice, Inbred C57BL , Spermatogenesis , Spermatogonia , Testis , Animals , Male , Mice , Spermatogonia/cytology , Spermatogonia/metabolism , Spermatogenesis/genetics , Spermatogenesis/physiology , Testis/metabolism , Testis/cytology , Cell Self Renewal , Adult Germline Stem Cells/metabolism , Adult Germline Stem Cells/cytology , Cells, Cultured , Receptors, Nicotinic/metabolism , Receptors, Nicotinic/genetics , Mice, Inbred Strains , Cell Differentiation , Cell Proliferation , Stem Cells/cytology , Stem Cells/metabolism , Mice, TransgenicABSTRACT
BACKGROUND: Transvaginal Natural Orifice Transluminal Endoscopy (vNOTES) is regarded as a challenging surgical technique to learn but is promising in reducing perioperative pain and significantly improves the cosmetic outcomes. Previous studies on the learning curve analysis of vNOTES mainly focuses on the hysterectomy approach, while the vNOTES ovarian cystectomy's learning curve was merely reported though more frequently performed than vNOTES hysterectomy. Therefore, this study seeks to analyze the learning curve of three surgeons with varying levels of experience in performing endoscopic surgery and vaginal surgeries for the treatment of ovarian cysts using vNOTES. METHODS: A total of 127 patients with ovarian cysts of a variety of pathological types were treated by ovarian vNOTES performed by three surgeons of different levels of endoscopic and transvaginal surgical experience. Each surgeon's learning curve was plotted using the Cumulative Sum method and divided into three or four phases of technique learning at the turning point of the learning curve. The sociodemographic and clinical features of patients in each phase were then compared and factors potentially associated with operation time were also screened. RESULTS: The learning curve was presented in four phases. The operation time (OT) was significantly shorter in phases II (53.66 ± 16.55 min) and IV (54.39 ± 23.45 min) as compared with phases I (68.74 ± 15.85) and III (75.93 ± 30.55) (p < 0.001). More cases of serve pelvic adhesion and endometrioma were assigned in the later phases. The OT of endometriotic cysts had much longer than that of non-endometriotic cysts(62.57 ± 18.64 min vs. 49.88 ± 14.26 min, p = 0.15) The presence of pelvic adhesion [adjusted odds ratio (OR) 7.149 (0.506, 13.792), p = 0.035] and bilateral cyst [adjusted OR 16.996 (2.155, 31.837), p = 0.025], max diameter of cyst[adjusted OR 2.799 (0.174, 5.425), p = 0.037], and individual surgeon [adjusted OR -6.118 (-11.814, -0.423), p = 0.035] were significantly associated with OT. CONCLUSION: There learning curve of ovarian vNOTES has four phases. ovarian vNOTES could be mastered after performing seven, nine, and 16 cases by surgeons #1, 2 and 3 respectively, in gynecologic endoscopic surgeries. TRIAL REGISTRATION: ChiCTR2200059282 (Registered on April 28th, 2022).
Subject(s)
Learning Curve , Natural Orifice Endoscopic Surgery , Operative Time , Ovarian Cysts , Humans , Female , Natural Orifice Endoscopic Surgery/methods , Natural Orifice Endoscopic Surgery/statistics & numerical data , Retrospective Studies , Adult , Ovarian Cysts/surgery , Middle Aged , Vagina/surgery , Clinical Competence/statistics & numerical data , Cohort StudiesABSTRACT
OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is considered to have the advantages of completely scarless, less postoperative pain, earlier flatus, and faster postoperative recovery. However, posterior myoma are relatively difficult to operate through vNOTES in the conventional lithotomy position. Thus, we innovated the application of prone position in the removal of posterior myoma in vNOTES. The aim of this study is the comparison of myomectomy outcomes of patient for single posterior myoma in prone and lithotomy position. DESIGN: A single-center, prospective study. SETTING: A university teaching hospital. PATIENTS: A total of 81 patients with posterior myoma who underwent myomectomy in vNOTES from January 2021 to December 2022. INTERVENTIONS: The patients underwent myomectomy in vNOTES in prone or lithotomy position. MEASUREMENTS AND MAIN RESULTS: Among the patients who underwent vNOTES myomectomy, 29 (35.8%) were in the lithotomy position group, and 52 (64.2%) in the prone position group. Of note, 4 (4.9%) patients underwent a conversion to LESS during the operation-3 in the lithotomy and 1 in the prone position group. And a patient in the lithotomy position group underwent resurgery for hemostasis due to postoperative pelvic bleeding. Compared with the lithotomy position, prone position significantly shortens the operation time (12.3, 95% CI: 6.811, 17.761. p = .009) without increasing the complications and postoperative discomfort of patients. CONCLUSION: Compared to the lithotomy position, the prone position provides greater convenience for operation and exhibits a lower rate of surgical conversion during the removal of single posterior myomas via vNOTES. Further, for patients selecting vNOTES, surgeons need to conduct sufficient preoperative evaluation, timely hemostasis during surgery, and timely surgical conversion if necessary to ensure patient safety.
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BACKGROUND: Peutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS. CASE PRESENTATION: Here, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive "cosmos pattern" resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a "quick-up and slow-down" pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC. CONCLUSIONS: Multimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.
SYNOPSIS: We reported multimodal ultrasonographical characteristics of a case of Peutz-Jeghers syndrome-related gastric-type endocervical adenocarcinoma (G-EAC), indicating the potential use of multimodal ultrasonography for G-EAC diagnosis.
ABSTRACT
In this study, a novel metal-dielectric film mode filter structure that can flexibly regulate the transverse mode inside vertical-cavity surface-emitting lasers (VCSELs) is proposed. The number, volume, and stability of transverse modes inside the VCSEL can be adjusted according to three key parameters-the oxide aperture, the metal aperture, and the distance between the oxide aperture and the metal aperture-to form a flexible window, and a new parameter is defined to describe the mode identification. This study provides a complete simulation theory basis and calculation method, which is of great significance for the optical mode control in VCSELs.
ABSTRACT
Blue lasers are integral to a variety of applications, including marine communication, underwater resource exploration, cold laser processing, laser medicine, and beyond. Vertical external cavity surface-emitting lasers (VECSELs) have the advantages of high output power and tunable wavelength, and can output blue laser via frequency doubling. In this article, a new type of intracavity beam control external-cavity structure is introduced. The laser beam waist is effectively adjusted by intracavity beam control, and the frequency conversion efficiency is improved. A laser cavity stability analysis model was developed to investigate the impact of laser cavity lens parameters and relative positions on stability. The external resonant cavity of VECSELs utilizes two optical lenses to position the beam waist near the laser output coupling mirror and locates the frequency doubling crystal at a high optical power density position to optimize frequency conversion efficiency. The VECSEL straight external-cavity structure achieves a frequency conversion efficiency of up to 60.2% at 488 nm, yielding a blue laser output exceeding 1.3 W. The full width at half maximum of the 488 nm spectrum measures approximately 0.23 nm. This intracavity beam-controlled direct external-cavity structure effectively mitigates laser mode leakage and shows potential for the development of an efficient and compact blue laser source.
ABSTRACT
DNA methylation is widely found in higher plants and can control gene expression by regulation without changing the DNA sequence. In this study, the whole-genome methylation map of sugar beet was constructed by WGBS (whole-genome bisulfite sequencing) technology, and the results of WGBS were verified by bisulfite transformation, indicating that the results of WGBS technology were reliable. In addition, 12 differential methylation genes (DMGs) were identified, which were related to carbohydrate and energy metabolism, pollen wall development, and endogenous hormone regulation. Quantitative real-time PCR (qRT-PCR) showed that 75% of DMG expression levels showed negative feedback with methylation level, indicating that DNA methylation can affect gene expression to a certain extent. In addition, we found hypermethylation inhibited gene expression, which laid a foundation for further study on the molecular mechanism of DNA methylation at the epigenetic level in sugar beet male sterility.
Subject(s)
Beta vulgaris , DNA Methylation , Sulfites , Beta vulgaris/genetics , Plant Infertility/genetics , Vegetables , SugarsABSTRACT
PURPOSE: Identifying the temporal pattern of recurrence and prognostic biomarkers would further help improve the efficacy of chimeric antigen receptor (CAR) -T therapy. METHODS: We examined the prognoses of 119 patients after sequential infusion of anti-CD19 and anti-CD22, a cocktail of 2 single-target CAR (CAR19/22) T cells in an open-label, single-center clinical trial (ChiCTR-OPN-16008526). And we, from a 70-biomarker panel, identified candidate cytokines that might predict the treatment failure, including primary non-response (NR) and early relapse (ER). RESULTS: In our study, 3 (11.5%) patients with B-cell acute lymphoblastic leukemia (B-ALL) and 9 (12.2%) cases of B-cell non-Hodgkin lymphoma (NHL) failed to respond to sequential CAR19/22 T-cell infusion (NR). A total of 11 (42.3%) B-ALL patients and 30 (52.7%) B-NHL patients had relapses during follow-up. Most recurrence events (67.5%) occurred within six months of sequential CAR T-cell infusion (ER). We found that macrophage inflammatory protein (MIP)-3α was a highly sensitive and specific prognostic predictor for patients with NR/ER and those attaining over-6-month remission. Patients who had higher MIP3α levels after sequential CAR19/22 T-cell infusion had significantly favorable progression-free survival (PFS) than their counterparts with relatively lower MIP3α expression. Our experiments demonstrated that MIP3α could enhance the therapeutic effect of CAR-T cells by promoting T-cell infiltration into and enriching memory-phenotype T cells in the tumor environment. CONCLUSION: This study showed that relapse occurred mainly within six months after sequential CAR19/22 T-cell infusion. Moreover, MIP3α could act as a valuable post-infusion biomarker for identifying patients with NR/ER.
Subject(s)
Burkitt Lymphoma , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Prognosis , Immunotherapy, Adoptive , T-Lymphocytes , Recurrence , Antigens, CD19ABSTRACT
AIMS: To investigate the perioperative outcomes and sexual function of patients undergoing repeated transvaginal natural orifice transluminal endoscopic surgery (vNOTES). METHODS: We retrieved the records of patients who underwent vNOTES twice at our institute between April 2019 and December 2022 and analyzed their baseline information and perioperative complications, and compared the pre- and postoperative sexual function of both vNOTES. RESULTS: Patients' mean age and body mass index were 29.00 ± 3.59 and 30.4 ± 4.00 years and 21.89 ± 3.69 and 22.76 ± 3.88 kg/m2 , respectively, when receiving the first and second vNOTES. Ectopic pregnancy was the most frequent indication for vNOTES, with 7 cases in the first vNOTES and 11 cases in repeated vNOTES. The interval between the two vNOTESs ranged from 9 days to 38 months. The operation duration (63.33 ± 13.71 vs. 67.33 ± 22.51 min, p = 0.723), intraoperative estimated blood loss (32.00 ± 20.42 vs. 30.00 ± 9.26 mL, p = 0.429), and duration of postoperative hospital stay (2.20 ± 0.56 vs. 2.40 ± 0.51 days, p = 0.082) of both vNOTESs were comparable. No significant differences were found in any of the domains in the comparison of pre-first and post-first vNOTES, pre-second and post-second vNOTES, and pre-first and post-second vNOTES female sexual function index. None of the patients delivered after the second vNOTES. CONCLUSION: Repeated vNOTES is safe and feasible. No significant change in the patients' sexual function was found in our cohort after the first and second vNOTES.
ABSTRACT
We characterize laser generation in an ultralong air cavity (several meters in length) using an optical-pumped semiconductor gain chip for laser wireless charging applications. The study realizes laser generation in an external air cavity with a length of 200 cm, for the first time, and achieves a maximum output laser power of more than 86.3 mW. Furthermore, the laser oscillation can be maintained even when the output mirror of laser is off-axis within 1.6 cm. Thus, a long external cavity laser would ease the alignment between the laser beam and charging terminal, making it suitable for laser wireless charging applications.
ABSTRACT
BACKGROUND: Cadmium (Cd) is a toxic heavy metal that is harmful to the environment and human health. Cd pollution threatens the cultivation of rice (Oryza sativa L.) in many countries. Improving rice performance under Cd stress could potentially improve rice productivity. RESULTS: In this study, 9 growth traits of 188 different cultivated rice accessions under normal and Cd stress conditions were found to be highly variable during the seedling stage. Based on ~3.3 million single nucleotide polymorphisms (SNPs), 119 Cd-mediated growth response (CGR) quantitative trait loci (QTL) were identified by a genome-wide association study (GWAS), 55 of which have been validated by previously reported QTL and 64 were new CGR loci. Combined with the data from the GWAS, transcriptome analysis, gene annotations from the gene ontology (GO) Slim database, and annotations and functions of homologous genes, 148 CGR candidate genes were obtained. Additionally, several reported genes have been found to play certain roles in CGRs. Seven Cd-related cloned genes were found among the CGR genes. Natural elite haplotypes/alleles in these genes that increased Cd tolerance were identified by a haplotype analysis of a diverse mini core collection. More importantly, this study was the first to uncover the natural variations of 5 GST genes that play important roles in CGRs. CONCLUSION: The exploration of Cd-resistant rice germplasm resources and the identification of elite natural variations related to Cd-resistance will help improve the tolerance of current major rice varieties to Cd, as well as provide raw materials and new genes for breeding Cd-resistant varieties.
Subject(s)
Cadmium/pharmacology , Genes, Plant , Oryza/growth & development , Oryza/genetics , Soil Pollutants/pharmacology , Alleles , Gene Expression Profiling , Genome, Plant , Genome-Wide Association Study , Oryza/drug effects , Plant Development/genetics , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Rice plants suffer from the rising temperature which is becoming more and more prominent. Mining heat-resistant genes and applying them to rice breeding is a feasible and effective way to solve the problem. RESULT: Three main biomass traits, including shoot length, dry weight, and fresh weight, changed after abnormally high-temperature treatment in the rice seedling stage of a recombinant inbred lines and the natural indica germplasm population. Based on a comparison of the results of linkage analysis and genome-wide association analysis, two loci with lengths of 57 kb and 69 kb in qDW7 and qFW6, respectively, were associated with the rice response to abnormally high temperatures at the seedling stage. Meanwhile, based on integrated transcriptome analysis, some genes are considered as important candidate genes. Combining with known genes and analysis of homologous genes, it was found that there are eight genes in candidate intervals that need to be focused on in subsequent research. CONCLUSIONS: The results indicated several relevant loci, which would help researchers to further discover beneficial heat-resistant genes that can be applied to rice heat-resistant breeding.
Subject(s)
Genes, Plant , Hot Temperature , Oryza/growth & development , Oryza/genetics , Seedlings/growth & development , Seedlings/genetics , Stress, Physiological/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant , Genetic Linkage , Genetic Variation , Genome-Wide Association Study , GenotypeABSTRACT
CTRP9 has been reported to regulate lipid metabolism and exert cardioprotective effects, yet its role in high-fat diet (HFD)-induced cardiac lipotoxicity and the underlying mechanisms remain unclear. In the current study, we established HFD-induced obesity model in wild-type (WT) or CTRP9 knockout (CTRP9-KO) mice and palmitate-induced lipotoxicity model in neonatal rat cardiac myocytes (NRCMs) to investigate the effects of CTRP9 on cardiac lipotoxicity. Our results demonstrated that the HFD-fed CTRP9-KO mice accentuated cardiac hypertrophy, fibrosis, endoplasmic reticulum (ER) stress-initiated apoptosis and oxidative stress compared with the HFD-fed WT mice. In vitro, CTRP9 treatment markedly alleviated palmitate-induced oxidative stress and ER stress-induced apoptosis in NRCMs in a dose-dependent manner. Phosphorylated AMPK at Thr172 was reduced, and phosphorylated mammalian target of rapamycin (mTOR) was strengthened in the heart of the HFD-fed CTRP9-KO mice compared with the HFD-fed control mice. In vitro, AMPK inhibitor compound C significantly abolished the effects of CTRP9 on the inhibition of the apoptotic pathway in palmitate-treated NRCMs. In a further mechanistic study, CTRP9 enhanced expression of phosphorylated LKB1 at Ser428 and promoted LKB1 cytoplasmic localization. Besides, silencing of LKB1 gene by lentivirus significantly prohibited activation of AMPK by CTRP9 and partially eliminated the protective effect of CTRP9 on the cardiac lipotoxicity. These results indicate that CTRP9 exerted anti-myocardial lipotoxicity properties and inhibited cardiac hypertrophy probably through the LKB1/AMPK signalling pathway.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adiponectin/metabolism , Cardiomegaly/metabolism , Diet, High-Fat/adverse effects , Glycoproteins/metabolism , Myocytes, Cardiac/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/physiology , Animals , Apoptosis/physiology , Endoplasmic Reticulum Stress/physiology , Fibrosis/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress/physiology , Phosphorylation/physiologyABSTRACT
BACKGROUND: Salinity is one of the most serious threats to world agriculture. An important sugar-yielding crop sugar beet, which shows some tolerance to salt via a mechanism that is poorly understood. Proteomics data can provide important clues that can contribute to finally understand this mechanism. RESULTS: Differentially abundant proteins (DAPs) in sugar beet under salt stress treatment were identified in leaves (70 DAPs) and roots (76 DAPs). Functions of these DAPs were predicted, and included metabolism and cellular, environmental information and genetic information processing. We hypothesize that these processes work in concert to maintain cellular homeostasis. Some DAPs are closely related to salt resistance, such as choline monooxygenase, betaine aldehyde dehydrogenase, glutathione S-transferase (GST) and F-type H+-transporting ATPase. The expression pattern of ten DAPs encoding genes was consistent with the iTRAQ data. CONCLUSIONS: During sugar beet adaptation to salt stress, leaves and roots cope using distinct mechanisms of molecular metabolism regulation. This study provides significant insights into the molecular mechanism underlying the response of higher plants to salt stress, and identified some candidate proteins involved in salt stress countermeasures.
Subject(s)
Beta vulgaris/physiology , Plant Leaves/metabolism , Plant Proteins/analysis , Plant Roots/metabolism , Salt Stress/physiology , Adaptation, Physiological , Computational Biology , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Proteomics/methods , SalinityABSTRACT
Pneumolysin (PLY), a pore-forming cytotoxin and a major virulence determinant, is a member of the cholesterol-dependent cytolysin (CDC) family and essential for promoting Streptococcus pneumoniae (S.pneumoniae) infection. Due to the action characteristics of hemolysin itself, the pneumolysin released after killing bacteria with conventional antibiotics still has the ability to damage host cells; therefore, drug treatments directly inhibiting hemolysin activity are the most effective. Hemolysis assays were used to confirm that quercetin can inhibit the activity of PLY, protecting cells in vitro, and an oligomerization assay was used to determine the mechanism of quercetin to suppress PLY activity. Live/Dead testing, lactate dehydrogenase (LDH) release analysis and a murine model of endonasal pulmonary infection were used to explore the capability of quercetin to protect cells and mice from S. pneumoniae-mediated damage in vivo and in vitro. The results indicated that quercetin significantly reduced PLY-induced hemolytic activity and cytotoxicity via repressing the formation of oligomers. In addition, treatment with quercetin can reduce PLY-mediated cell injury, improve the survival rate of mice infected with a lethal dose of S. pneumoniae, alleviate the pathological damage of lung tissue and inhibit the release of cytokines (IL-1ß and TNF-α) in bronchoalveolar lavage fluid. Considering the importance of these events in antimicrobial resistant S. pneumoniae pathogenesis, our results indicated that quercetin may be a novel potential drug candidate for the treatment of clinical pneumococcal infections.
Subject(s)
Pneumococcal Infections/drug therapy , Quercetin/pharmacology , Animals , Bacterial Proteins/drug effects , Cell Line , Hemolysis/drug effects , Interleukin-1beta/drug effects , Lung/microbiology , Lung/pathology , Mice , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/metabolism , Streptolysins , Tumor Necrosis Factor-alpha/drug effects , Virulence/drug effectsABSTRACT
Sugar beet is an important sugar-yielding crop with some tolerance to salt, but the mechanistic basis of this tolerance is not known. In the present study, we have used whole-transcriptome RNA-seq and degradome sequencing in response to salt stress to uncover differentially expressed (DE) mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in both leaves and roots. A competitive endogenous RNA (ceRNA) network was constructed with the predicted DE pairs, which revealed regulatory roles under salt stress. A functional analysis suggests that ceRNAs are implicated in copper redistribution, plasma membrane permeability, glycometabolism and energy metabolism, NAC transcription factor and the phosphoinositol signaling system. Overall, we conducted for the first time a full transcriptomic analysis of sugar beet under salt stress that involves a potential ceRNA network, thus providing a basis to study the potential functions of lncRNAs/circRNAs.
Subject(s)
Beta vulgaris/genetics , Exome Sequencing/methods , Gene Expression Profiling/methods , Gene Regulatory Networks , RNA, Plant/genetics , Salt Stress/genetics , Gene Expression Regulation, Plant/drug effects , Gene Ontology , MicroRNAs/genetics , Plant Leaves/genetics , Plant Roots/genetics , RNA, Circular/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Salinity , Sodium Chloride/pharmacologyABSTRACT
The countermeasure of driver fatigue is valuable for reducing the risk of accidents caused by vigilance failure during prolonged driving. Listening to the radio (RADIO) has been proven to be a relatively effective "in-car" countermeasure. However, the connectivity analysis, which can be used to investigate its alerting effect, is subject to the issue of signal mixing. In this study, we propose a novel framework based on clustering and entropy to improve the performance of the connectivity analysis to reveal the effect of RADIO to maintain driver alertness. Regardless of reducing signal mixing, we introduce clustering algorithm to classify the functional connections with their nodes into different categories to mine the effective information of the alerting effect. Differential entropy (DE) is employed to measure the information content in different brain regions after clustering. Compared with the Louvain-based community detection method, the proposed method shows more superior ability to present RADIO effectin confused functional connection matrices. Our experimental results reveal that the active connection clusters distinguished by the proposed method gradually move from frontal region to parieto-occipital regionwith the progress of fatigue, consistent with the alpha energy changes in these two brain areas. The active class of the clusters in parieto-occipital region significantly decreases and the most active clusters remain in the frontal region when RADIO is taken. The estimation results of DE confirm the significant change (p < 0.05) of information content due to the cluster movements. Hence, preventing the movement of the active clusters from frontal region to parieto-occipital region may correlate with maintaining driver alertness. The revelation of alerting effect is helpful for the targeted upgrade of fatigue countermeasures.
ABSTRACT
This study was aimed to explore the role of C1q/TNF-related protein 9 (CTRP9) on atherosclerotic lesion formation. A recombinant lentiviral vector carrying mouse CTRP9 (Lv-CTRP9) was injected intravenously into apolipoprotein E knockout (ApoE-/-) mice given a high-fat diet (HFD). CTRP9 overexpression substantially attenuated atherosclerotic lesion size of mice. The accumulation of macrophages and smooth muscle cells (SMCs) was significantly decreased in atherosclerotic regions with CTRP9 overexpression by immunohistochemical analysis. In addition, CTRP9 downregulated the expressions of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α), two main proinflammatory cytokines in atherosclerosis. Furthermore, the autophagy level remarkably increased which was presented by microtubule-associated protein light chain 3B (LC3B) conversion and sequestosome 1 (SQSTM1/p62) degradation. Further study showed that CTRP9 increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation in vivo. These observations reveal that CTRP9 exerts a protecting role in early atherosclerotic lesions and its anti-atherosclerotic effect is associated with autophagy induction through AMPK/mTOR signaling pathway.
Subject(s)
Adiponectin/biosynthesis , Atherosclerosis/metabolism , Glycoproteins/biosynthesis , Macrophages/metabolism , Myocytes, Smooth Muscle/metabolism , Signal Transduction , Adiponectin/genetics , Animals , Atherosclerosis/genetics , Atherosclerosis/pathology , Chemokine CCL2/biosynthesis , Chemokine CCL2/genetics , Glycoproteins/genetics , Lentivirus , Macrophages/pathology , Mice , Mice, Knockout, ApoE , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Myocytes, Smooth Muscle/pathology , Phosphorylation/genetics , Proteolysis , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Transduction, Genetic , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Electrospinning is a facile technique to fabricate nanofibrous materials with adjustable structure, property, and functions. Electrospun materials have exhibited wide applications in the fields of materials science, biomedicine, tissue engineering, energy storage, environmental science, sensing, and others. In this review, we present recent advance in the fabrication of nanoparticles (NPs)-based materials interfaces through electrospinning technique and their applications for high-performance sensors. To achieve this aim, first the strategies for fabricating various materials interfaces through electrospinning NPs, such as metallic, oxide, alloy/metal oxide, and carbon NPs, are demonstrated and discussed, and then the sensor applications of the fabricated NPs-based materials interfaces in electrochemical, electric, fluorescent, colorimetric, surface-enhanced Raman scattering, photoelectric, and chemoresistance-based sensing and detection are presented and discussed in detail. We believe that this study will be helpful for readers to understand the fabrication of functional materials interfaces by electrospinning, and at the same time will promote the design and fabrication of electrospun nano/micro-devices for wider applications in bioanalysis and label-free sensors.
ABSTRACT
BACKGROUND: Acute myeloid leukemia can develop as myoblasts infiltrate into organs and tissues anywhere other than the bone marrow, which called extramedullary infiltration (EMI), indicating a poor prognosis. Circular RNAs (circRNAs) are a novel class of non-coding RNAs that feature covalently closed continuous loops, suggesting their potential as micro RNA (miRNA) "sponges" that can participate in biological processes and pathogenesis. However, investigations on circRNAs in EMI were conducted rarely. In this study, the overall alterations of circRNAs and their regulatory network between EMI and non-EMI AML were delineated. METHODS: CircRNA and whole genome microarrays derived from EMI and non-EMI AML bone marrow mononuclear cells were carried out. Functional analysis was performed via Gene Ontology and KEGG test methods. The speculated functional roles of circRNAs were based on mRNAs and predicted miRNAs that played intermediate roles. Integrated bioinformatic analysis was conducted to further characterize the circRNA/miRNA/mRNA regulatory network and identify the functions of distinct circRNAs. The Cancer Genome Atlas (TCGA) data were acquired to evaluate the poor prognosis of distinct target genes of circRNAs. Reverse transcription-quantitative polymerase chain reaction was conducted to identify the expression of has_circRNA_0004520. Connectivity map (CMap) analysis was further performed to predict potential therapeutic agents for EMI. RESULTS: 253 circRNAs and 663 genes were upregulated and 259 circRNAs and 838 genes were downregulated in EMI compared to non-EMI AML samples. GO pathways were enriched in progress including cell adhesion (GO:0030155; GO:0007155), migration (GO:0016477; GO:0030334), signal transduction (GO:0009966; GO:0007165) and cell-cell communication. Overlapping circRNAs envolved in pathways related to regulate cell-cell crosstalk, 17 circRNAs were chosen based on their putative roles. 7 target genes of 17 circRNAs (LRRK1, PLXNB2, OLFML2A, LYPD5, APOL3, ZNF511, and ASB2) indicated a poor prognosis, while overexpression of PAPLN and NRXN3 indicated a better one based on data from TCGA. LY-294002, trichostatin A and SB-202190 were identified as therapeutic candidates for EMI by the CMap analysis. CONCLUSION: Taken together, this study reveals the overall alterations of circRNA and mRNA involved in EMI and suggests potential circRNAs may act as biomarkers and targets for early diagnosis and treatment of EMI.