ABSTRACT
Silver nanowires (AgNWs) have attractive applications in the fabrication of flexible electronics because of their adequate electrical conductivity, mechanical properties, and oxidation resistance. However, the film produced by AgNW ink needs to be sintered at temperatures above 200 °C to obtain high electrical conductivity, which is incompatible with commonly used flexible substrates such as paper or polymer materials. In this study, the AgNW network was decorated byin situreduced Ag particles (AgPs) to improve the structural integrity and conductivity of the film. After sintering at 80 °C, the pores and voids within the AgNW network were filled with Ag particles smaller than 200 nm, and the porosity of the film was markedly reduced. The lowest resistivity value was 3.9 × 10-5Ω cm after sintering at 100 °C, only 10.8% and 8.5% of the resistivity values of the films produced from AgNW and ion inks, respectively. During sintering, Ag nucleated on the surface of AgNWs, and its growth and agglomeration resulted in interconnections between the AgNWs and Ag particles. Thereafter, the bridging and filling effect of the Ag particles facilitated the formation of a compact and firm network, improving the film conductivity. The line film printed from the composite ink with 10 layers exhibited a low resistivity of 7.3 × 10-7Ω·m. Even after 5000 bending cycles, the resistivity of the line only increased by 4.47 × 10-6Ω·cm from the initial value. The composite ink reported in this study is a promising candidate for the low-cost printing of ultralow-power-consumption wearable electronic devices.
ABSTRACT
Mineral processing wastewater contains a lot of organic matter and heavy metal ions, and poor self-degradation ability makes it a key treatment object in environmental treatment. Photocatalysis is a promising technology to efficiently mineralize refractory contaminants from wastewater. In this work, 3D flower-like S-scheme N-Bi2O2CO3/g-C3N4 heterostructures were successfully constructed by hydrothermal method with the auxiliary of ionic liquids. The photocatalytic experiments show that the catalytic activity of heterojunction photocatalysts was significantly higher than that of bare g-C3N4 and N-Bi2O2CO3 for the degradation of two pollutants. NBOC/CN-2 shows the highest photocatalytic performance, and the degradation efficiency of sodium isobutyl xanthate (SIBX) on NBOC/CN-2 is 1.85 and 3 times that of bare g-C3N4 and Bi2O2CO3, respectively. The degradation efficiency of m-Cresol on NBOC/CN-2 is 8.34 and 6.93 times that of bare g-C3N4 and N-Bi2O2CO3, respectively. This significantly enhanced photocatalytic activity is attributed to the formation of flower-like heterojunctions, which can greatly increase the specific surface area and facilitate the separation and migration of photogenerated carriers. Total organic carbon (TOC) experiment proves that the two pollutants are effectively mineralized under the action of the prepared photocatalyst. The degradation path of m-Cresol degradation products was inferred based on the ion fragments. The capture experiment and Nitro-blue tetrazolium (NBT)-â¢O2- measurement show that superoxide radical plays a major role in photocatalytic degradation. The outstanding stability of the prepared flower-like heterojunction samples was examined by cyclic experiments. The S-scheme charge transfer mechanism has been proposed to explain the boosted activity of the flower-like heterojunction photocatalyst. This work provides a new idea for the design of efficient and stable g-C3N4-based photocatalyst for the photocatalytic degradation of refractory wastewater.
Subject(s)
Environmental Pollutants , Ionic Liquids , Wastewater , CresolsABSTRACT
Hydrogel flexible strain sensors, renowned for their high stretchability, flexibility, and wearable comfort, have been employed in various applications in the field of human motion monitoring. However, the predominant method for fabricating hydrogels is the template method, which is particularly inefficient and costly for hydrogels with complex structural requirements, thereby limiting the development of flexible hydrogel electronic devices. Herein, we propose a novel method that involves using microgels to modify a hydrogel solution, printing the hydrogel ink using an electrohydrodynamic printing device, and subsequently forming the hydrogel under UV illumination. The resulting hydrogel exhibited a high tensile ratio (639.73%), high tensile strength (0.4243 MPa), and an ionic conductivity of 0.2256 S/m, along with excellent electrochemical properties. Moreover, its high linearity and sensitivity enabled the monitoring of a wide range of subtle changes in human movement. This novel approach offers a promising pathway for the development of high-performance, complexly structured hydrogel flexible sensors.
ABSTRACT
Neuronal activity in the prefrontal cortex (PFC) controls dominance hierarchies in groups of animals. Dopamine (DA) strongly modulates PFC activity mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs). Still, it is unclear how these two subpopulations of DA receptor-expressing neurons in the PFC regulate social dominance hierarchy. Here, we demonstrate distinct roles for prefrontal D1R- and D2R-expressing neurons in establishing social hierarchy, with D1R+ neurons determining dominance and D2R+ neurons for subordinate. Ex vivo whole-cell recordings revealed that the dominant status of male mice correlates with rectifying AMPAR transmission and stronger excitatory synaptic strength onto D1R+ neurons in PFC pyramidal neurons. In contrast, the submissive status is associated with higher neuronal excitability in D2R+ neurons. Moreover, simultaneous manipulations of synaptic efficacy of D1R+ neurons in dominant male mice and neuronal excitability of D2R+ neurons of their male subordinates switch their dominant-subordinate relationship. These results reveal that prefrontal D1R+ and D2R+ neurons have distinct but synergistic functions in the dominance hierarchy, and DA-mediated regulation of synaptic strengths acts as a powerful behavioral determinant of intermale social rank.SIGNIFICANCE STATEMENT Dominance hierarchy exists widely among animals who confront social conflict. Studies have indicated that social status largely relies on the neuronal activity in the PFC, but how dopamine influences social hierarchy via subpopulation of prefrontal neurons is still elusive. Here, we explore the cell type-specific role of dopamine receptor-expressing prefrontal neurons in the dominance-subordinate relationship. We found that the synaptic strength of D1 receptor-expressing neurons determines the dominant status, whereas hyperactive D2-expressing neurons are associated with the subordinate status. These findings highlight how social conflicts recruit distinct cortical microcircuits to drive different behaviors and reveal how D1- and D2-receptor enriched neurocircuits in the PFC establish a social hierarchy.
Subject(s)
Dopaminergic Neurons/metabolism , Prefrontal Cortex/metabolism , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Social Dominance , Animals , Male , Mice , Patch-Clamp TechniquesABSTRACT
OBJECTIVES: Long non-coding RNAs (lncRNAs) play important roles in RA pathogenesis. However, specific lncRNAs that regulate gene expression in RA pathogenesis are poorly known. This study was undertaken to characterize a novel lncRNA (lnc-RNU12) that has a lower-than-normal expression level in RA patients. METHODS: We performed initial genome-wide lncRNA microarray screening in peripheral blood mononuclear cells from 28 RA cases and 18 controls. Multiple methods were used to validate the detected associations between lncRNAs and RA. Furthermore, we identified the source and characteristics of the highlighted lncRNAs, detected the target genes, and determined the functional effect on immune cells through lncRNA knock-down in Jurkat T cell lines. RESULTS: lnc-RNU12 was downregulated in peripheral blood mononuclear cells and T cell subtypes of RA patients and was genetically associated with RA risk. lnc-RNU12 mediates the effect of microbiome alterations on RA risk. Activation of T cells caused low expression of lnc-RNU12. Knock-down of lnc-RNU12 in Jurkat T cells caused cell cycle S-phase arrest and altered the expression of protein-coding genes related to the cell cycle and apoptosis (e.g. c-JUN, CCNL2, CDK6, MYC, RNF40, PKM, VPS35, DNAJB6 and FLCN). Finally, c-JUN and CCNL2 were identified as target genes of lnc-RNU12 at the mRNA and protein expression levels. RNA-binding protein immunoprecipitation assays verified the interaction between lnc-RNU12 and the two proteins (c-Jun and cyclin L2) in Jurkat cells. CONCLUSIONS: Our study suggested that lnc-RNU12 was involved in the pathogenesis of RA by influencing the T cell cycle by targeting c-JUN and CCNL2.
Subject(s)
Arthritis, Rheumatoid , RNA, Long Noncoding , Humans , Cell Cycle , Cyclins , HSP40 Heat-Shock Proteins , Leukocytes, Mononuclear/metabolism , Molecular Chaperones , Nerve Tissue Proteins , RNA, Long Noncoding/genetics , T-Lymphocytes/metabolism , Transcription Factors , Proto-Oncogene Proteins c-jun/metabolismABSTRACT
We have previously shown that Liang-Yan-Yi-Zhen-San (LYYZS), an ancient Chinese herbal formula, can promote the browning of white adipose tissue. In this study, we sought to determine which active ingredients of LYYZS mediated its effects on the browning of white adipose tissue. Employing ultra-high performance liquid chromatography-Q-Exactive HF mass spectrometry, a total of 52 LYYZS ingredients were identified. On this basis, 1,560 ingredient-related targets of LYYZS were screened using the HERB databases. Meanwhile, RNA sequencing analysis of the inguinal white adipose tissue of mice produced a total of 3148 genes that were significantly differentially expressed following LYYZS treatment and differentially expressed genes regarded as browning-related targets. Through the network pharmacological analysis, a total of 136 intersection targets were obtained and an ingredient-target-pathway network was established. According to network pharmacology analysis, 10 ingredients containing trans-cinnamaldehyde, genistein, daidzein, calycosin, arginine, coumarin, oleic acid, isoleucine, palmitic acid and tyrosine were regarded as active ingredients of browning of white adipose tissue. Integrated evaluation using chemical analysis, transcriptomics and network pharmacology provides an efficient strategy for discovering the active ingredients involved in how LYYZS promotes the browning of white adipose tissue.
Subject(s)
Drugs, Chinese Herbal , Network Pharmacology , Animals , Mice , Chromatography, High Pressure Liquid , Transcriptome , Adipose Tissue, Brown , Gas Chromatography-Mass Spectrometry , Adipose Tissue, White , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistryABSTRACT
BACKGROUND: Trophinin-associated protein (TROAP) mediates embryonic transfer, regulates microtubules, and is associated with the biological behavior of various cancers. However, there is limited information on the role of TROAP in glioma. METHODS AND RESULTS: We obtained clinical information on 1948 patients with glioma from The Cancer Genome Atlas, Gene Expression Omnibus and the Chinese Glioma Genome Atlas. Basal assays were used to measure changes in TROAP expression levels in high-grade glioma cell lines and in normal human astrocytes. Quantitative reverse transcription polymerase chain reaction assays showed that TROAP expression was higher in glioma cell lines than in normal astrocytes. The expression level of TROAP in 749 glioma was significantly higher than that in 228 normal brain tissues using Student's t test. The expression of TROAP has a positive relationship with the clinical characteristics of poor prognosis, such as WHO grade, age and has negatively correlated with the indicators of beneficial prognosis, such as IDH mutation and 1p19q co-deletion. Kaplan-Meier survival curves, single multifactor analysis were used to analyze correlations between TROAP and clinical features and prognosis of gliomas. In addition, TROAP overexpression was an independent risk factor for glioma and was associated with reduced overall survival of patients with glioma particularly in patients with WHO grade III and grade IV glioma. Gene set enrichment analysis showed that homologous recombination, cell cycle, and p53 signaling pathways were enriched in samples overexpressing TROAP. CONCLUSION: TROAP is a potential risk factor associated with poor prognosis in patients with glioma and may act as a highly specific biomarker, offering the possibility of individualized glioma treatment.
Subject(s)
Brain Neoplasms , Glioma , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Cycle , Glioma/metabolism , Humans , Kaplan-Meier EstimateABSTRACT
AIMS: Acute lung injury (ALI) is a leading cause of mortality as a result of inflammatory cytokine overexpression and increased rates of apoptosis. Therapies for ALI are yet to be thoroughly investigated. Recent evidence has shown that irisin exerts protective effects against many types of pathologies. The present study aimed to determine the function of irisin in an ALI mouse model induced by lipopolysaccharide (LPS) and the corresponding underlying mechanisms at the tissue, cellular, and molecular levels. MAIN METHODS: We assessed irisin function in A549 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The cell apoptosis was evaluated by flow cytometry. Western blotting and RT-PCR were used to test expression level. Animal models of ALI was established. KEY FINDINGS: We found that irisin treatment maintained lung weight, significantly reduced inflammatory cytokine expression, and alleviated lung injury by downregulating miR-199a. In LPS-stimulated cells, forced miR-199a expression downregulated Rad23b expression by targeting its 3' untranslated region, indicating that Rad23b is a direct target of miR-199a. SIGNIFICANCE: These findings reveal that irisin can alleviate ALI by inhibiting miR-199a and upregulating Rad23b expression, suggesting that irisin has clinical potential for the treatment of ALI.
Subject(s)
Acute Lung Injury/metabolism , Cytokines/metabolism , DNA-Binding Proteins/metabolism , Fibronectins/pharmacology , MicroRNAs/metabolism , Acute Lung Injury/chemically induced , Animals , Apoptosis/drug effects , DNA-Binding Proteins/drug effects , Disease Models, Animal , Fibronectins/metabolism , Lipopolysaccharides/pharmacology , Lung/pathology , Mice, Inbred C57BL , MicroRNAs/drug effects , Signal Transduction/drug effects , Up-Regulation/drug effectsABSTRACT
Fragile X syndrome (FXS) is the leading monogenic form of intellectual disability and autism, with patients exhibiting numerous auditory-related phenotypes during their developmental period, including communication, language development, and auditory processing deficits. Despite FXS studies describing excitatory-inhibitory (E-I) imbalance in the auditory circuit and an impaired auditory critical period, evaluation of E-I circuitry maturation in the auditory cortex of FXS models remains limited. Here, we examined GABAA receptor (GABAAR)-mediated inhibitory synaptic transmission within the auditory cortex, characterizing normal intracortical circuit development patterns in wild-type (WT) mice and examining their dysregulation in developing Fmr1 knock-out (KO) mice. Electrophysiological recordings revealed gradual developmental shifts in WT L4-L2/3 connectivity, where circuit excitability significantly increased after critical period onset. KO mice exhibited accelerated developmental shifts related to aberrant GABAergic signaling. Specifically, Fmr1 KO L2/3 pyramidal neurons have enhanced developmental sensitivity to pharmacological GABAAR modulators, altered maturation of GABAAR voltage-dependent conductance, with additional presynaptic GABA release alterations. These differences are further accompanied by alterations in developmental long-term potentiation. Together, our results suggest that altered GABAergic signaling within developing Fmr1 KOs impairs the normal patterning of E-I circuit and synaptic plasticity maturation to contribute to the impaired auditory cortex critical period and functional auditory deficits in FXS.
Subject(s)
Auditory Cortex , Fragile X Syndrome , Animals , Disease Models, Animal , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Mice , Mice, Knockout , Receptors, GABA-A , Synaptic TransmissionABSTRACT
Directly measuring particulate matters (PM) from chimneys in an industrial park is difficult due to it being hard to reach the peak heights. A self-developed PM detector on an unmanned aerial vehicle (UAV) had been deployed to directly measure the PM emissions in smoke plumes from chimneys in a textile dyeing industrial park. Compared with a commercial PM device (LD-5R, SIBATA, Kyoto, Japan), the self-developed detector showed similar performance with a good correlation (R2 varying from 0.911 to 0.951) in simultaneously vertical PM measurements on UAV. The PM emissions from chimneys after different textile treating processes, including pigment printing, dyeing process, and digital printing, were investigated. PM mass concentrations and particle number concentrations (PNC) in different sizes were found to be significantly higher in pigment printing than those in dyeing process and digital printing by 2 or 3 times after electrostatic precipitation. The activated carbon adsorption and electrostatic precipitation were the major PM controlling techniques in the park. The PM mass concentrations and PNC were the highest in the process of dyeing after activated carbon adsorption with the concentrations of PM1 (1000 µg·m-3), PM2.5 (1600 µg·m-3), and PM10 (2000 µg·m-3), respectively. According to the results of PM and PNC, PM2.5 was found to be the dominant particles accounting for 99% of the PM emissions. It may be due to the high temperature in thermo-fixing machine, which is beneficial to the PM2.5 generation. This study revealed PM2.5 was the dominant particles to be reduced in textile dyeing enterprises to mitigate PM pollution.
Subject(s)
Air Pollutants , Particulate Matter , Air Pollutants/analysis , Charcoal , China , Environmental Monitoring/methods , Particle Size , Particulate Matter/analysis , Rivers , Smoke , TextilesABSTRACT
Over the past several years, a new generation of quantum simulations has greatly expanded our understanding of charge density wave phase transitions in Hamiltonians with coupling between local phonon modes and the on-site charge density. A quite different, and interesting, case is one in which the phonons live on the bonds, and hence modulate the electron hopping. This situation, described by the Su-Schrieffer-Heeger (SSH) Hamiltonian, has so far only been studied with quantum Monte Carlo in one dimension. Here we present results for the 2D SSH model, show that a bond ordered wave (BOW) insulator is present in the ground state at half filling, and argue that a critical value of the electron-phonon coupling is required for its onset, in contradistinction with the 1D case where BOW exists for any nonzero coupling. We determine the precise nature of the bond ordering pattern, which has hitherto been controversial, and the critical transition temperature, which is associated with a spontaneous breaking of Z_{4} symmetry.
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BACKGROUND: DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines. METHODS: In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination. RESULTS: The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity. CONCLUSION: The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate.
Subject(s)
Herpesvirus 1, Bovine , Polyethyleneimine , Vaccines, DNA , Viral Vaccines/administration & dosage , Administration, Intranasal , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Herpesvirus 1, Bovine/genetics , Immunity, Cellular , Magnetic Phenomena , Mice , Mice, Inbred BALB C , Plasmids/administration & dosage , Plasmids/genetics , Vaccine Development , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Viral Vaccines/geneticsABSTRACT
It is important to evaluate the complex coronary artery disease in the diagnosis and treatment of coronary heart disease.The SYNTAX score based on invasive coronary angiography (ICA) (also referred to as ICA-SYNTAX score) plays a positive role in the selection of revascularization of complex coronary artery disease and the prediction of adverse events.The development of coronary computed tomography angiography (CCTA) technology promotes the clinical application of SYNTAX score (CCTA-SYNTAX score) based on coronary CTA, and also enriches the examination methods of patients with coronary heart disease. The CCTA-SYNTAX score has the advantages of non-invasiveness, simple operation, good reproducibility, and relatively low cost, which can make it play an increasingly important role in the diagnosis of coronary heart disease. A number of foreign studies have confirmed that CCTA-SYNTAX score is highly correlated with ICA-SYNTAX score, which further promotes the study of CCTA-SYNTAX score in revascularization of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and adverse event prediction.Therefore, the CCTA-SYNTAX score can be an auxiliary method for the ICA-SYNTAX score, as the first choice for preoperative evaluation and postoperative review of patients with coronary heart disease.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Humans , Reproducibility of Results , Treatment OutcomeABSTRACT
Inflammatory cytokines were involved in pathological conditions of osteoporosis (OP). However, the specific OP-associated inflammatory cytokines are still awaiting to be detected by using a systemic method. Herein, we adopted an extreme sampling scheme and examined inflammatory cytokines between subjects with low and high bone mineral density (BMD) through protein microarray. First, 8 candidate cytokines including B lymphocyte chemoattractant (BLC), osteopontin (OPN) and insulin-like growth factor-binding protein 4 (IGFBP4) were identified in the discovery extreme sampling subgroup. Then, the different expressions for BLC, OPN and IGFBP4 were validated and replicated in two independent extreme sampling subgroups. Further functional experiments showed that the cytokine BLC was involved in bone metabolism by inhibiting bone formation and promoting bone resorption. Together, this study further revealed that inflammatory cytokines were closely related with OP, and that they highlighted critical roles of BLC in the pathogenesis of OP.
Subject(s)
Cytokines/metabolism , Inflammation/metabolism , Osteoporosis, Postmenopausal/metabolism , Plasma/metabolism , Postmenopause/metabolism , 3T3 Cells , Aged , Animals , Bone Density/physiology , Bone Resorption/metabolism , Cell Line , China , Female , Humans , Mice , Osteopontin/metabolism , Protein Array Analysis/methods , RAW 264.7 CellsABSTRACT
In this erratum the set of Eqs. (2a) and (2b), Eqs. (4) and (5), and the corresponding figure and values in the text of Opt. Lett.45, 4215 (2019)OPLEDP0146-959210.1364/OL.44.004215 have been updated.
ABSTRACT
Type 2 diabetes (T2D) is characterized by islet ß-cell dysfunction and impaired suppression of glucagon secretion of α-cells in response to oral hyperglycaemia. Bile acid (BA) metabolism plays a dominant role in maintaining glucose homeostasis. So we evaluated the association of fasting serum total bile acids (S-TBAs) with insulin sensitivity, islet ß-cell function and glucagon levels in T2D. Total 2,952 T2D patients with fasting S-TBAs in the normal range were recruited and received oral glucose tolerance tests for determination of fasting and postchallenge glucose, C-peptide and glucagon. Fasting and systemic insulin sensitivity were assessed by homeostasis model assessment (HOMA) and Matsuda index using C-peptide, i.e., ISHOMA-cp and ISIM-cp, respectively. Islet ß-cell function was assessed by the insulin-secretion-sensitivity-index-2 using C-peptide (ISSI2cp). The area under the glucagon curve (AUCgla) was used to assess postchallenge glucagon. The results showed ISHOMA-cp, ISIM-cp and ISSI2cp decreased, while AUCgla notably increased, across ascending quartiles of S-TBAs but not fasting glucagon. Moreover, S-TBAs were inversely correlated with ISHOMA-cp, ISIM-cp and ISSI2cp (r = -0.21, -0.15 and -0.25, respectively, p < 0.001) and positively correlated with AUCgla (r = 0.32, p < 0.001) but not with fasting glucagon (r = 0.033, p = 0.070). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the S-TBAs were independently associated with ISHOMA-cp (ß = -0.04, t = -2.82, p = 0.005), ISIM-cp (ß = -0.11, t = -7.05, p < 0.001), ISSI2cp (ß = -0.15, t = -10.26, p < 0.001) and AUCgla (ß = 0.29, t = 19.08, p < 0.001). Increased fasting S-TBAs are associated with blunted fasting and systemic insulin sensitivity, impaired islet ß-cell function and increased glucagon levels in response to glucose challenge in T2D.
Subject(s)
Bile Acids and Salts/metabolism , Blood Glucose/metabolism , C-Peptide/metabolism , Diabetes Mellitus, Type 2/metabolism , Glucagon/metabolism , Insulin Resistance , Insulin Secretion , Insulin-Secreting Cells/metabolism , Adult , Bile Acids and Salts/blood , C-Peptide/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Female , Glucagon/blood , Glucose Tolerance Test , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle AgedABSTRACT
OBJECTIVE: To investigate the diagnostic value of miRNA let-7a, high mobility group A2 (HMGA2) expression and serum miRNA let-7a level in pancreatic cancer. METHODS: From January 2014 to January 2019, 60 patients with pancreatic cancer were collected for fresh pancreatic ductal adenocarcinoma tissue and normal pancreatic tissue adjacent to the cancer after the operation. Serum samples before and after operation were also collected, while 60 healthy people were enrolled as the control group. The expression of miRNA let-7a (qRT-PCR) and HMGA2 (qRT-PCR and Western blot) in cancer and adjacent normal tissues were measured. The serum level of miRNA let-7a was detected by qRT-PCR. The relationship between miRNA let-7a and HMGA2 expression and the clinicopathological features of pancreatic cancer was analyzed. The diagnostic value of serum miRNA let-7a pre-operation in patients with pancreatic cancer was also analyzed with ROC curve. RESULTS: Compared with normal tissues adjacent to the cancer, the expression level of miRNA let-7a in pancreatic cancer tissues decreased ( t=20.291, P<0.01), and the expression of HMGA2 mRNA increased ( t=46.681, P<0.01). The expression of HMGA2 protein in cancer tissues was higher than that in normal tissues adjacent to the cancer ( t=22.973, P<0.01). The serum level of miRNA let-7a in pancreatic cancer patients was significantly lower than that in healthy controls ( t=24.854, P<0.01). The relative level of serum miRNA let-7a at 1 week after surgery was significantly lower than that before surgery in pancreatic cancer patients ( t=6.885, P<0.01). There was a positive correlation between cancer tissue and serum miRNA let-7a expression 1 week after surgery ( r=0.411, P=0.000). The relative expression levels of miRNA let-7a and HMGA2 in pancreatic cancer tissues were significantly different in different TNM stages and lymph node metastasis ( P<0.05). The area under curve of pre-operation serum miRNA let-7a for the diagnosis of pancreatic cancer was 0.823 ( 95% confidence interval: 0.665-0.917); when the optimal cut-off value of miRNA let-7a was 0.614, the sensitivity was 82.3%, the specificity was 74.1%. CONCLUSION: The expression of HMGA2 may be involved in the invasion and metastasis of pancreatic cancer. The level of serum miRNA let-7a may provide a reference for the diagnosis and postoperative monitoring of pancreatic cancer.
Subject(s)
Gene Expression Regulation, Neoplastic , HMGA2 Protein , MicroRNAs , Pancreatic Neoplasms , Gene Expression Profiling , HMGA2 Protein/genetics , Humans , MicroRNAs/blood , MicroRNAs/genetics , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , RNA, Messenger/geneticsABSTRACT
OBJECTIVES: To investigate the relationship among coronary artery calcification score (CACS), the number of calcification vessels, SYNTAX score and GRACE score in patients with coronary atherosclerotic heart disease (CHD). METHODS: The CACS, calcification vessel number, SYNTAX score, and GRACE score were collected or calculated from 214 CHD patients admitted in Haikou People's Hospital from January 2014 to April 2019. Patients were assigned into several groups according to the CACS and calcification vessel number, and then to compare the differences in SYNTAX and GRACE scores between groups. Spearman correlation coefficient was used to analyze the correlation between CACS or calcification vessel number and SYTAX score or GRACE score. Regression of binary logistic was used to analyze independent risk factors for coronary calcification. The diagnostic values of the CACS and calcification vessel number for predicting CHD, and SYNTAX score and GRACE score high-risk group were evaluated by the receiver operator characteristic (ROC) curve. RESULTS: Spearman correlation analysis showed that CACS was positively correlated with SYTAX score (r=0.505, P<0.01) or GRACE score (r=0.195, P<0.01). The number of calcified vessels was positively correlated with the SYNTAX score (r=0.533, P<0.01), but not with the GRACE score (r=-0.14, P=0.899). Regression of binary logistic showed that male and SYTAX scores were independent risk factors for coronary artery calcification (P<0.05). The analysis of ROC curve showed that the CACS was of good value in the diagnosis of CHD (AUC=0.756, P<0.01) and SYNTAX score high-risk group (AUC=0.781, P<0.01), while it was of lower value in the diagnostic of the GRACE score high-risk group (AUC=0.698, P<0.01). The value of calcification vessel number in the diagnosis of CHD (AUC=0.763, P<0.01) and the SYNTAX score high-risk group (AUC=0.868, P<0.01) was good, but that in the diagnosis of the GRACE score high-risk group (AUC=0.601, P=0.07) was not statistically significant. CONCLUSIONS: In patients with suspected CHD, CACS and calcification vessel number can predict the severity of CHD and the risk of future cardiovascular events. Measuring the CACS and the number of calcification vessels before coronary angiography has certain clinical significance for predicting the severity of coronary lesion and formulating the treatment plan.
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Genetic variants have potential influence on DNA methylation and thereby regulate mRNA expression. This study aimed to comprehensively reveal the relationships among SNP, methylation and mRNA, and identify methylation-mediated regulation patterns in human peripheral blood mononuclear cells (PBMCs). Based on in-house multi-omics datasets from 43 Chinese Han female subjects, genome-wide association trios were constructed by simultaneously testing the following three association pairs: SNP-methylation, methylation-mRNA and SNP-mRNA. Causal inference test (CIT) was used to identify methylation-mediated genetic effects on mRNA. A total of 64,184 significant cis-methylation quantitative trait loci (meQTLs) were identified (FDR < 0.05). Among the 745 constructed trios, 464 trios formed SNP-methylation-mRNA regulation chains (CIT). Network analysis (Cytoscape 3.3.0) constructed multiple complex regulation networks among SNP, methylation and mRNA (eg a total of 43 SNPs simultaneously connected to cg22517527 and further to PRMT2, DIP2A and YBEY). The regulation chains were supported by the evidence from 4DGenome database, relevant to immune or inflammatory related diseases/traits, and overlapped with previous eQTLs from dbGaP and GTEx. The results provide new insights into the regulation patterns among SNP, DNA methylation and mRNA expression, especially for the methylation-mediated effects, and also increase our understanding of functional mechanisms underlying the established associations.
Subject(s)
DNA Methylation/genetics , Genomics/methods , Leukocytes, Mononuclear/metabolism , Polymorphism, Single Nucleotide/genetics , Adult , Databases, Genetic , Female , Gene Expression Regulation , Gene Regulatory Networks , Genome-Wide Association Study , Humans , Inflammation/genetics , Linkage Disequilibrium/genetics , Quantitative Trait Loci/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
During 2014-2017, we screened for Rickettsia japonica infection in Xinyang, China, and identified 20 cases. The major clinical manifestations of monoinfection were fever, asthenia, myalgia, rash, and anorexia; laboratory findings included thrombocytopenia and elevated hepatic aminotransferase concentrations. Physicians in China should consider R. japonica infection in at-risk patients.