ABSTRACT
Two-dimensional (2D) Fe chalcogenides with their rich structures and properties are highly desirable for revealing the torturous transition mechanism of Fe chalcogenides and exploring their potential applications in spintronics and nanoelectronics. Hydrostatic pressure can effectively stimulate phase transitions between various ordered states, allowing one to successfully plot a phase diagram for a given material. Herein, the structural evolution and transport characteristics of 2D FeTe were systematically investigated under extreme conditions by comparing two distinct symmetries, i.e., tetragonal (t) and hexagonal (h) FeTe. We found that t-FeTe presented a pressure-induced transition from an antiferromagnetic state to a ferromagnetic state at â¼3 GPa, corresponding to the tetragonal collapse of the layered structure. Contrarily, the ferromagnetic order of h-FeTe was retained up to 15 GPa, which was evidently confirmed by electrical transport and Raman measurements. Furthermore, T-P phase diagrams for t-FeTe and h-FeTe were mapped under delicate critical conditions. Our results can provide a unique platform to elaborate the extraordinary properties of Fe chalcogenides and further develop their applications.
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Persistent activation of estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in driving the progression of estrogen receptor positive (ER+) breast cancer (BC). In the current study, LINC00173, a long non-coding RNA, was found to bind both ERα and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFα) factor (LITAF), then cooperatively to inhibit ERα protein degradation by impeding the nuclear export of ERα. Concurrently, LITAF was found to attenuate TNFα transcription after binding to LINC00173, and this attenuating transcriptional effect was quite significant under lipopolysaccharide stimulation. Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF-transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression.
Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Estrone , RNA, Long Noncoding , Transcription Factors , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics , Female , Estrone/metabolism , Estrone/pharmacology , Estrone/analogs & derivatives , Transcription Factors/metabolism , Transcription Factors/genetics , Tumor Necrosis Factor-alpha/metabolism , MCF-7 Cells , Cell Line, Tumor , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Apoptosis/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Proteolysis/drug effects , Animals , Mice , Gene SilencingABSTRACT
Multi-component composite materials with a magnetic-dielectric synergistic effect exhibit satisfactory electromagnetic wave absorption performance. However, the effective construction of the structure for these multi-component materials to fully exploit the advantages of each component remains a challenge. Inspired by natural biomass, this study utilizes wood as the raw material and successfully prepares high-performance MoS2@Gd2O3/Mxene loaded porous carbon aerogel (MGMCA) composite material through a one-pot hydrothermal method and carbonization treatment process. With a delicate structural design, the MGMCA is endowed with abundant heterogeneous interface structures, favorable impedance matching characteristics, and a magnetic-dielectric synergistic system, thus demonstrating multiple electromagnetic wave loss mechanisms. Benefiting from these advantages, the obtained MGMCA exhibits outstanding electromagnetic wave absorption performance, with a minimum reflection loss of -57.5 dB at an ultra-thin thickness of only 1.9 mm. This research proposes a reliable strategy for the design of multi-component composite materials, providing valuable insight for the design of biomass-based materials as electromagnetic wave absorbers.
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Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of liver disease that has reached its last stage. Over the past few years, evidence for miRNAs' centrality in NAFLD pathogenesis has accumulated. According to some studies, miR-574-5p plays a role in lipid metabolism. However, research on the relationship between miR-574-5p and NAFLD is lacking. For in vivo experiments, we induced the NAFLD mice model with a high-fat diet (HFD). AgomiR-574-5p was injected intravenously into HFD-fed mice for eight weeks, and qPCR was used to identify the expression of miR-574-5p in the serum. In in vitro experiments, The treatment of L-O2 cells with a miR-574-5p mimic resulted in a significant reduction in lipid deposition, suggesting that miR-574-5p can inhibit lipid accumulation and lipid formation induced by OA. The dual-luciferase reporter gene assay revealed that miR-574-5p targets the 3' UTR region of HOXC6 directly. We discovered that OA-induced lipid accumulation in hepatocytes might be mediated through the miR-574-5p-HOXC6 signaling axis. Additional research is required in order to determine the specific mechanism by which HOXC6 downstream pathways are involved in the miR-574-5p induced lipid uptake.
Subject(s)
MicroRNAs , Non-alcoholic Fatty Liver Disease , Animals , Mice , Diet, High-Fat/adverse effects , Hepatocytes/metabolism , Lipid Metabolism/genetics , Lipids , Lipogenesis/genetics , Liver/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
Antibiotics and available chlorine coexist in multiple aquatic environments, and thus antibiotics and their chlorinated disinfection by-products (Cl-DBPs) have been a great concern for the nature and human health. Herein, the degradation intermediates and transformation pathways of sulfamethoxazole (SMX) Cl-DBPs in constructed wetlands (CWs) were investigated. A total of five SMX Cl-DBPs and their twenty degradation products in CWs was identified in this study. SMX and its Cl-DBPs influenced the biodegradation rather than the adsorption process in CWs. S1 atom on sulfonyl group of SMX had the strongest nucleophilicity, and was most vulnerable for nucleophilic attack. N5 and N7 on amino groups, and C17 on the methyl group had great electronegativity, and were susceptible to electrophilic reactions. S1-N5 and S1-C8 bonds of SMX are the most prone to cleavage, followed by C11-N5, C16-C17, and C12-N7. The chlorination of SMX mainly occurred at S1, N5, and N7 sites, and went through S-C cleavage, S-N hydrolysis, and desulfonation. The biodegradation of SMX Cl-DBPs in CWs mainly occurred at S1, N5, N7, C8, and C17 sites, and went through processes including oxidation of methyl, hydroxyl and amino groups, desulfonation, decarboxylation, azo bond cleavage, benzene ring cleavage, ß-oxidation of fatty acids under the action of coenzymes. Over half of the SMX Cl-DBPs had greater bioaccumulation potential than their parent SMX, but the environmental risk of SMX Cl-DBPs was effectively reduced through the degradation by CWs.
Subject(s)
Disinfection , Halogenation , Sulfamethoxazole , Water Pollutants, Chemical , Wetlands , Sulfamethoxazole/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Disinfectants/chemistry , Biodegradation, Environmental , Water Purification/methodsABSTRACT
Leptospirosis is a recurring but neglected zoonotic disease caused by pathogenic Leptospira. The explicit underlying mechanism of necroptosis and its role in Leptospira infection have not yet been elucidated. Here we reported that leptospiral pathogen-associated molecular patterns, lipopolysaccharide, and glycolipoprotein activate the necroptotic RIPK1-RIPK3-MLKL cascade through the TLR4 signaling pathway in mouse macrophages. Using the murine acute leptospirosis model, we reveal that abolition of necroptosis exhibited significantly improved outcomes in acute phases, with enhanced eradication of Leptospira from liver, mild clinical symptoms, and decreased cytokine production. RIPK3 was also found to exert a necroptosis-independent function in CXCL1 production and neutrophil recruitment, with the consequence of improved Leptospira control. These findings improve our understanding of the mechanism of Leptospira-macrophage interactions, indicating potential therapeutic values by targeting necroptosis signaling pathways.
Subject(s)
Leptospira , Leptospirosis , Mice , Animals , Lipopolysaccharides , Necroptosis , Leptospirosis/pathology , Leptospira/metabolism , Macrophages/metabolism , Receptor-Interacting Protein Serine-Threonine KinasesABSTRACT
Fabrication of transition-metal catalytic materials is regarded as a promising strategy for developing high-performance sodium-selenium (Na-Se) batteries. However, more systematic explorations are further demanded to find out how their bonding interactions and electronic structures can affect the Na storage process. This study finds that lattice-distorted nickel (Ni) structure can form different bonding structures with Na2 Se4 , providing high activity to catalyze the electrochemical reactions in Na-Se batteries. Using this Ni structure to prepare electrode (Se@NiSe2 /Ni/CTs) can realize rapid charge transfer and high cycle stability of the battery. The electrode exhibits high storage performance of Na+ ; i.e., 345 mAh gâ»1 at 1 C after 400 cycles, and 286.4 mAh gâ»1 at 10 C in rate performance test. Further results reveal the existence of a regulated electronic structure with upshifts of the d-band center in the distorted Ni structure. This regulation changes the interaction between Ni and Na2 Se4 to form a Ni3 -Se tetrahedral bonding structure. This bonding structure can provide higher adsorption energy of Ni to Na2 Se4 to facilitate the redox reaction of Na2 Se4 during the electrochemical process. This study can inspire the design of bonding structure with high performance in conversion-reaction-based batteries.
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BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS. METHODS: We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects. RESULTS: ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins. CONCLUSIONS: These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.
Subject(s)
Cytokines , Fatigue Syndrome, Chronic , Humans , Proteomics , Cell Communication , Case-Control StudiesABSTRACT
Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.
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AIM: To assess the servant leadership behaviour of head nurse and its linkage with nurse work engagement in China. DESIGN: A cross-sectional study. METHODS: A anonymous investigation with the stratified cluster randomized sampling of nurse was conducted in Hunan Province of China in December 2020. We administered the Perceived Head Nurse Service Leadership Behaviour Scale and the Chinese version of Utrecht work engagement scale to survey, and analyse its relationships by multiple linear regression. RESULTS: A number of 890 nurses participated in this study. The average score of the perceived servant leadership of head nurse reported by nurses was 78.90 ± 14.04, which was at a medium level. Among its six dimensions, the dimension of promote nurse development scored highest (16.04 ± 2.84), while the dimension of dedication scored lowest (11.39 ± 2.46). Official nurses reported higher perceived servant leadership scores of head nurses than those who were employed and temporary nurses (b = 1.727, 95% CI: 0.054-3.400); nurses in tertiary hospitals reported higher perceived servant leadership scores of head nurses than nurses in primary and secondary hospitals (b = 2.703, 95% CI: 0.305-5.100); and lower perceived servant leadership scores were associated with nurses' job overtime (b = -4.935, 95% CI: -6.891 to -2.978). Nurses' perceived servant leadership of head nurses were positively associated with nurses' work engagement (r = 0.336, p < .05). Multiple linear regression analysis indicated that the perceived servant leadership of head nurse affected nurses' work engagement strongly (b = 0.585, 95% CI: 0.479-0.691). CONCLUSION: The servant leadership behaviour of head nurse in China was at the medium level, which was positively associated with nurses' work engagement. Further research should improve the power of the servant leadership behaviour of head nurse by integrating additional training, policies and support. IMPACT: It is time to consider the servant leadership behaviour of head nurses and its linkage with nurses' work engagement in China seriously, and address the policies, guidelines, curriculum, and practice culture. PATIENT OR PUBLIC CONTRIBUTION: The study was conducted to explore the situation of servant leadership behaviour of head nurses and its linkage with nurses' work engagement in China, which did not include input from the public or the intended participants.
Subject(s)
Nurses , Nursing, Supervisory , Humans , Leadership , Work Engagement , Cross-Sectional Studies , China , Surveys and Questionnaires , Job SatisfactionABSTRACT
The atmospheric chemical mechanism is an essential component of airshed models used for investigating the chemical behaviors and impacts of species. Since the first tropospheric chemical mechanism was proposed in the 1960s, various mechanisms including Master Chemical Mechanism (MCM), Carbon Bond Mechanism (CBM), Statewide Air Pollution Research Center (SAPRC) and Regional Atmospheric Chemistry Mechanism (RACM) have been developed for different research purposes. This work summarizes the development and applications of these mechanisms, introduces their compositions and lumping methods, and compares the ways the mechanisms treat radicals with box model simulations. CBM can reproduce urban pollution events with relatively low cost compared to SAPRC and RACM, whereas the chemical behaviors of radicals and the photochemical production of ozone are described in detail in RACM. The photolysis rates of some oxygenated compounds are low in SAPRC07, which may result in underestimation of radical levels. As an explicit chemical mechanism, MCM describes the chemical processes of primary pollutants and their oxidation products in detail. MCM can be used to investigate certain chemical processes; however, due to its large size, it is rarely used in regional model simulations. A box model case study showed that the chemical behavior of OH and HO2 radicals and the production of ozone were well described by all mechanisms. CBM and SAPRC underestimated the radical levels for different chemical treatments, leading to low ozone production values in both cases. MCM and RACM are widely used in box model studies, while CBM and SAPRC are often selected in regional simulations.
Subject(s)
Air Pollutants , Air Pollution , Ozone , Air Pollutants/analysis , Air Pollution/analysis , Ozone/chemistryABSTRACT
Efficient urchin-like Pt nanoparticles@Bi2S3 (PtNPs@Bi2S3) composite materials were prepared by a composite soft template synthesis of urchin-like Bi2S3 and then the microwave-assisted growth of PtNPs onto the Bi2S3 nanostructure. For the first time, an accurate electrochemical glucose biosensor was fabricated via immobilizing glucose oxidase (GOx) on PtNPs@Bi2S3. The PtNPs@Bi2S3 composite was investigated via scanning electron microscopy, electrochemical impedance spectroscopy, Fourier transform infrared spectroscopy, and cyclic voltammetry. The PtNPs@Bi2S3 composite provides a large surface area to load a large number of enzyme molecules, which maintains the biological activity. PtNPs loaded on Bi2S3 enhanced the conductivity and improved the direct electron transfer of the proposed biosensor with the synergistic effect. The fabricated electrochemical biosensor possesses high sensitivity, and a wide linear range from 0.003 mM to 0.1 mM and 0.1 mM to 1.9 mM. Moreover, the biosensor has outstanding stability, superior selectivity and good repeatability, which can be utilized to monitor the glucose level in practical human serum. The PtNPs@Bi2S3 composite supplies a special matrix for immobilizing proteins and potential for establishing other effective biosensors.
Subject(s)
Biosensing Techniques , Dielectric Spectroscopy , Electrochemical Techniques , Electrodes , Enzymes, Immobilized , Glucose , Glucose Oxidase , Humans , Limit of DetectionABSTRACT
Oxygen reduction reaction (ORR) plays a key role in the field of fuel cells. Efficient electrocatalysts for the ORR are important for fuel cells commercialization. Pt and its alloys are main active materials for ORR. However, their high cost and susceptibility to time-dependent drift hinders their applicability. Satisfactory catalytic activity of nanostructured transition metal phthalocyanine complexes (MPc) in ORR through the occurrence of molecular catalysis on the surface of MPc indicates their potential as a replacement material for precious-metal catalysts. Problems of MPc are analyzed on the basis of chemical structure and microstructure characteristics used in oxygen reduction catalysis, and the strategy for controlling the structure of MPc is proposed to improve the catalytic performance of ORR in this review.
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An ultrasensitive multiplex surface-enhanced Raman scattering (SERS) immunoassay was developed using porous Au-Ag alloy nanoparticles (p-AuAg NPs) as Raman signal amplification probe coupling with encoded photonic crystal microsphere. p-AuAg NPs were synthesized and modified with the second antibody (Ab2) and Raman tag (mercaptobenzoic acid, MBA) to prepare a Raman signal-amplified probe. The high porosity of the p-AuAg NPs enables significant coupling of the localized surface plasmon resonance and thus abundant inherent hotspots for Raman signal enhancement. 3D-ordered silver nanoparticles-coated silica photonic crystal beads (Ag/SPCBs) were prepared as encoded SERS substrate for multiplex detection using their reflection peaks. The signal-amplified probe was used for multiplex detection of tumor markers carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP). The wide linear ranges of 10-7-103 ng/mL for CEA and 10-4-103 ng/mL for AFP with detection limits of 1.22 × 10-8 ng/mL and 2.47 × 10-5 ng/mL for CEA and AFP at a signal-to-noise ratio of 3 were obtained. The proposed multiplex SERS immunoassay method displays ultrahigh sensitivity, wide linear range, and excellent specificity, which can be successfully applied to measure clinical serum samples with satisfactory results. The research provides a novel SERS signal enhancement strategy for the multiplex bioassay.
Subject(s)
Alloys , Metal Nanoparticles , SilverABSTRACT
The balanced-field electromagnetic technique is an effective in-line inspection method for pipeline cracks. To address the problem that the interference signal generated by the tilt jitter of the sensor during the detection process affects the judgment of cracks, this paper proposes a method to differentiate the crack detection signal from the sensor jitter signal by using an amplitude-phase composite figure. The generation principle of the detection signal was analyzed by using the mutual inductance model, and the amplitude-phase composite figure was constructed by using the components of the detection signal after quadrature demodulation. The feasibility of using the phase as a signal discrimination feature was illustrated by finite element simulations, and the characteristics of the amplitude-phase composite figure were determined. The validity of the proposed method was verified experimentally. The results show that the crack detection signal and the signal generated by the sensor jitter are of the same frequency with similar waveforms and significantly different phases. The phase base value of the crack detection signal ranges from 35° to 55°, and the phase base value of the jitter signal is -4°. In terms of the characteristics of the amplitude-phase composite figure, the crack detection signal distribution is symmetrical about the origin in the first and third quadrants, and the axial crack is closer to the Y-axis than the circumferential crack; the jitter signal is distributed in the second and fourth quadrants and has a very small angle to the X-axis. In addition, the proposed method effectively weakens the observation of the phase noise region in the detection signal of the balanced-field electromagnetic technique.
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This study reports valence and arousal ratings for 11,310 simplified Chinese words, including 9774 two-character words, 949 three-character words, and 587 four-character words. These affective ratings are validated through comparisons with prior ratings of smaller word samples. All but four words included in this study are from the MEgastudy of Lexical Decision in Simplified CHinese (MELD-SCH) database. As age-of-acquisition ratings and concreteness ratings have recently become available for large portions of words in the MELD-SCH, the affective ratings not only further enrich the database as a valuable research tool, but also allow us to gain insight into a range of psycholinguistic constructs based on normative ratings of a large set of Chinese words. Cross-language comparisons of the valence ratings between Chinese words and English words appear to indicate cultural and sociopolitical influences reflected in affect representations.
Subject(s)
Emotions , Language , Arousal , China , Humans , PsycholinguisticsABSTRACT
Pancreatitis-associated proteins (PAPs) display multiple functions in visceral diseases. Previous studies showed that the expression level of PAP-I was low in the DRG of naive rats but was de novo expressed after peripheral nerve injury. However, its role in neuropathic pain remains unknown. We found that PAP-I expression was continuously upregulated in the DRG neurons from rat spared nerve injury models, and transported toward the spinal dorsal horn to act as a proinflammatory factor. Intrathecal delivery of PAP-I enhanced sensory hyperalgesia, whereas PAP-I deficiency by either gene knockout or antibody application alleviated tactile allodynia at the maintenance phase after spared nerve injury. Furthermore, PAP-I functioned by activating the spinal microglia via C-C chemokine receptor Type 2 that participated in neuropathic pain. Inhibition of either microglial activation or C-C chemokine receptor Type 2 abolished the PAP-I-induced hyperalgesia. Thus, PAP-I mediates the neuron-microglial crosstalk after peripheral nerve injury and contributes to the maintenance of neuropathic pain.SIGNIFICANCE STATEMENT Neuropathic pain is maladaptive pain condition, and the maintaining mechanism is largely unclear. Here we reveal that, after peripheral nerve injury, PAP-I can be transported to the spinal dorsal horn and is crucial in the progression of neuropathic pain. Importantly, we prove that PAP-I mainly functions through activating the spinal microglia via the CCR2-p38 MAPK pathway. Furthermore, we confirm that the proinflammatory effect of PAP-I is more prominent after the establishment of neuropathic pain, thus indicating that microglia also participate in the maintenance phase of neuropathic pain.
Subject(s)
Microglia/metabolism , Neuralgia/metabolism , Pancreatitis-Associated Proteins/metabolism , Peripheral Nerve Injuries/metabolism , Spinal Cord/metabolism , Animals , Ganglia, Spinal/metabolism , Hyperalgesia/metabolism , Male , Neurons/metabolism , Protein Transport/physiology , Rats , Rats, Sprague-Dawley , Signal Transduction/physiologyABSTRACT
BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive subtype of Non-Hodgkin's Lymphoma. CircRNA has shown great potential to become a biomarker in plasma. In this study, we aimed to determine circRNA for its diagnostic and prognostic value and biological function in NKTCL. METHOD: The circRNA microarray of plasma from NKTCL patients and healthy donors were conducted. The relative expressions of target circRNA were verified by qRT-PCR. We conducted function experiments in vitro and in vivo. Bioinformatics predicted the target miRNA of the target circRNA and the binding site was detected by the dual luciferase report assay. Downstream target protein was predicted and detected by western blot in vitro and immunohistochemistry in vivo. RESULT: By analyzing the plasma circRNA microarrays in NKTCL, 6137 circRNAs were up-regulated and 6190 circRNAs were down-regulated. The relative expressions of circADARB1 were significantly higher in NKTCL patients. The knockdown of circADARB1 inhibited proliferation of NKTCL cells in vitro and in vivo. CircADARB1 could bind to miR-214-3p in the downstream and regulate the expression of p-Stat3. In nude mice tumor tissue, p-Stat3 was under-expressed in the circADARB1 knockdown group. CONCLUSION: CircADARB1 was highly expressed in NKTCL plasma and circADARB1 was a potential biomarker to assist diagnosis and predict the response in NKTCL. CircADARB1 bound up to miR-214-3p and regulated p-Stat3.
ABSTRACT
CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor that is involved in adipocytic and monocytic differentiation. However, the physiological role of C/EBPß in megakaryocytes (MKs) is not clear. In this study, we investigated the effects of C/EBPß on the early-stage differentiation of MKs, and explored the potential mechanisms of action. We established a cytosine arabinoside-induced thrombocytopenia mouse model using C57BL/6 mice. In the thrombocytopenia mice, the platelet count was found to be decreased, and the mRNA and protein expression levels of C/EBPß in MKs were also reduced. Furthermore, the maturation of Dami (MKs cell line) cells was induced by phorbol 12-myristate 13-acetate. When C/EBPß was silenced in Dami cells by transfection using C/EBPß-small interfering RNA, the expression of MKs-specific markers CD41 and CD62P, was dramatically decreased, resulting in morphological changes and differentiation retardation in low ploidy, which were evaluated using flow cytometry, real-time polymerase chain reaction, western blot, and confocal microscopy. The mitogen activated protein kinase-extracellular signal-regulated kinase signaling pathway was found to be required for the differentiation of MKs; knockdown of C/EBPß in MEK/ERK1/2 pathway attenuated MKs differentiation. Overexpression of C/EBPß in MEK/ERK1/2 pathway inhibited by U0126 did not promote MKs differentiation. To the best of our knowledge, C/EBPß plays an important role in MKs differentiation and polyploidy cell cycle control. Taken together, C/EBPß may have thrombopoietic effects in the differentiation of MKs, and may assist in the development of treatments for various disorders.
Subject(s)
CCAAT-Enhancer-Binding Protein-beta/metabolism , Cell Differentiation , Megakaryocytes/cytology , Thrombopoiesis , Animals , CCAAT-Enhancer-Binding Protein-beta/deficiency , CCAAT-Enhancer-Binding Protein-beta/genetics , Cell Line , Gene Expression Regulation , Gene Knockdown Techniques , MAP Kinase Signaling System , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Time FactorsABSTRACT
BACKGROUND: Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People's Democratic Republic, Myanmar, and Viet Nam. METHODS: Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). RESULTS: A malaria elimination campaign in the 1950-1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the '1-3-7' surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. CONCLUSIONS: Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.