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1.
J Colloid Interface Sci ; 662: 109-118, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38340510

RESUMO

The impact of Indium (In) doping upon the catalytic performance of Pd-Cu/Al2O3 for carbon monoxide preferential oxidation (CO-PROX) in hydrogen (H2) rich atmosphere at low temperature has been studied. A series of catalysts with extremely low palladium (Pd) loading (0.06 wt%) are synthesized by the facile co-impregnation method. When the In/copper (Cu) atomic ratio equals 0.25, Pd-Cu-In0.25/Al2O3 can keep 40% CO conversion and 100% carbon dioxide (CO2) selectivity at least 120 min at 30 °C, which is significantly superior to the catalytic performance of Pd-Cu/Al2O3. The elaborate characterization findings reveal that the added In species to Pd-Cu/Al2O3 causes Indium oxide (In2O3) to generate, which produces the interaction of In2O3 with Pd-Cu/Al2O3, further promoting the dispersion of copper chloride hydroxide (Cu2Cl(OH)3). Moreover, the modification of In facilitates the re-oxidation of Pd0 to Pd+ through reducing the formation of palladium hydride (PdHx) during the CO-PROX reaction. Meanwhile, the addition of In leads to the decrease of Cu+ electron cloud density, making it easier to be oxidized to Cu2+. Collectively, the easy re-oxidation of Pd0 and Cu+ is favorable to fulfill the Wacker cycle between Pd and Cu species, thus improving the catalytic performance for CO-PROX.

2.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345986

RESUMO

BACKGROUND: von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD. METHODS: We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing. RESULTS: The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTO-CETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF: NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF: NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges. CONCLUSIONS: We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD.


Assuntos
Doenças de von Willebrand , Fator de von Willebrand , Masculino , Humanos , Adulto Jovem , Adulto , Fator de von Willebrand/genética , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/genética , Linhagem , Mutação , Fibrinogênio , China
3.
Sleep Breath ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37917283

RESUMO

BACKGROUND: Previous studies have revealed that sleep structure and hypoxemia are two important environmental factors for cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that the pathophysiological mechanisms between these two factors may also be involved in cognitive impairment in patients with OSAHS. Previous studies have suggested that alterations in serum glucose and lipid metabolism, inflammatory responses, and astrocyte markers not only contribute to sleep structural disorders in OSAHS but also affect the occurrence and development of this disease. Therefore, we hypothesized that alterations in the abovementioned indicators may be involved in cognitive impairment in OSAHS. Additionally, obesity is an important risk factor for OSAHS. This study therefore aimed to explore the correlation between serum indicators and cognitive impairment in patients with OSAHS. METHODS: Patients with OSAHS who underwent polysomnography in our hospital were recruited in this study. The overall cognitive function of patients were evaluated using the Mini mental State Examination (MMSE). Blood biochemical indicators such as glucose (GLU), triglycerides (TG), and triglyceride glucose (TyG) index were measured. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum glucagon-like peptide-1 receptor (GLP-1R), fibroblast growth factor 21 (FGF21), S100 calcium binding protein B (S100B), brain derived neurotrophic factor (BDNF), inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Spearman correlation analysis was used to determine if the indicator was related to cognitive function, and backward linear regression analysis was used to identify the main risk factors for cognitive impairment in non-obese and obese patients with OSAHS. RESULTS: Among 34 patients, 19 were non-obese and 15 were obese. Obese patients exhibited higher AHI compared to non-obese individuals, and the difference was statistically significant (p < 0.05). In non-obese patients, Spearman correlation analysis revealed a negative correlation between serum GLU, IL-4, and MMSE scores (p < 0.05); IL-6 was positively correlated with MMSE (p < 0.05). In addition, GLU and IL-6 were independently correlated with MMSE in non-obese patients (p < 0.05). In obese patients, serum TG and TyG were positively correlated with MMSE scores (p < 0.05); age, BMI, and IL-4 were negatively correlated with MMSE scores (p < 0.05). In addition, age and IL-4 were independently correlated with MMSE in obese patients (p < 0.05). CONCLUSIONS: Our data suggested that GLU and IL-6 were independently correlated with cognitive impairment in non-obese patients with OSAHS; age and IL-4 were independently correlated with cognitive impairment in obese patients. Early detection of this difference in heterogeneity may provide theoretical support for future investigations in prevention and treatment of cognitive impairment in patients with OSAHS.

4.
Clin Transl Sci ; 16(12): 2591-2603, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37786330

RESUMO

This study aimed to evaluate the bioequivalence between test tablet dacomitinib and reference product Vizimpro® under fasting and fed conditions and assess their pharmacokinetic (PK) and safety profiles for gaining marketing approval of the new generic drug. A single-center, randomized, open-label, single-dose, two-treatment, two-period, crossover bioequivalence study was conducted in healthy Chinese subjects. Eligible healthy subjects randomly received a single 45 mg dose of test or reference formulations with an administration sequence of test tablet (T), reference tablet (R), or (RT), under both fasting and fed conditions, and each single administration was followed by a 21-day washout period. Plasma concentrations and corresponding non-compartmental PK parameters of dacomitinib were determined. The 90% confidence intervals of the geometric mean ratio (GMR) (test/reference) for Cmax , AUC0-t , and AUC0-∞ , respectively, were 97.75%-119.99%, 101.00%-115.09%, and 100.27%-113.90% under fasting conditions and 95.20%-104.94%, 97.24%-102.23%, and 97.27%-101.88% under fed conditions, which were within the limits of 80%-125%. Under fasting and fed conditions, the PK characteristics of the test dacomitinib tablet and reference Vizimpro® were comparable; the two formulations of dacomitinib were demonstrated to be bioequivalent and well-tolerated in healthy Chinese volunteers.


Assuntos
Jejum , Humanos , Equivalência Terapêutica , Estudos Cross-Over , Voluntários Saudáveis , Comprimidos , China
6.
Transl Neurosci ; 14(1): 20220286, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37250142

RESUMO

Objective: MiRNAs play a key role in ischemic stroke (IS). Although miR-101-3p can participate in multiple disease processes, its role and mechanism in IS are not clear. The aim of the present study was to observe the effect of miR-101-3p activation on IS in young mice and the role of HDAC9 in this effect. Methods: The young mice were first subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery, and the cerebral infarct area was assessed with 2,3,5-triphenyltetrazolium chloride staining. Meanwhile, the expressions of miR-101-3p and HDAC9 were tested using RT-qPCR or western blot. Besides, neuron morphology and apoptosis were confirmed using Nissl staining and TUNEL staining. Results: We first verified that miR-101-3p was downregulated and HDAC9 was upregulated in the brain tissue of tMCAO young mice. Moreover, we proved that overexpression of miR-101-3p could improve cerebral infarction, neuronal morphology, and neuronal apoptosis in tMCAO young mice by lowering the expression of HDAC9. Conclusions: Activation of miR-101-3p can protect against IS in young mice, and its mechanism is relevant to the inhibition of HDAC9. Therefore, miR-101-3p and HDAC9 might be the latent targets for IS therapy.

7.
Sleep Breath ; 27(5): 1717-1724, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36586074

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a disease characterized with intermittent hypoxia and sleep fragmentation. Obesity and gender are major risk factors for the onset of OSAHS. Previous studies on obese men with OSAHS have been performed, while few studies on non-obese men with OSAHS have been carried out. The purpose of this study was to explore the clinical characteristics of polysomnography and blood biochemical indexes in non-obese men with OSAHS and to identify the possible influencing factors. METHODS: This retrospective study included patients with OSAHS who underwent polysomnography in our hospital. General clinical data such as overnight polysomnography and biochemical indicators were recorded. The patients were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSAHS and severe OSAHS. The differences in biochemical parameters such as the levels of γ-glutamine transaminase (GGT), triglyceride (TG), glucose (GLU), and sleep structure parameters such as N1, N2, slow-wave sleep (SWS), and rapid eye movement (REM) sleep were compared and analyzed. Spearman correlation analysis and logistic regression were used to identify the risk factors of non-obese men with OSAHS. ROC curves were used to evaluate the predictive ability of SWS and GGT on disease severity. RESULTS: Of 94 non-obese men with OSAHS, 49 had mild to moderate OSAHS and 45 had severe OSAHS. Our data suggested that the levels of low oxygen saturation (L-SaO2), mean oxygen saturation (M-SaO2), SWS, and GGT were significantly changed in the mild to moderate OSAHS group compared with the severe group (p < 0.05). For patients with OSAHS, the proportion of SWS in the group with severe OSAHS was higher than that in the mild to moderate group (p < 0.05), and the serum GGT enzyme levels were significantly elevated in the severe group compared to the mild to moderate group (p < 0.05). Using logistic regression analyses, our data revealed that both SWS and GGT enzyme levels were independent risk factors for AHI (p < 0.05). In addition, the results of correlation analysis indicated that SWS was related to triglyceride (TG), total cholesterol (TC), apolipoprotein E (APOE), and triglyceride glucose (TyG) index (p < 0.05); GGT was related to TG, TC, APOE, and TyG index (p < 0.05). Furthermore, SWS was independently associated with GGT (p < 0.05). The area under the ROC curve plotted with the combined coefficient of SWS and serum GGT was 0.728, which was predictive of the disease severity. CONCLUSIONS: These results suggest that SWS and GGT are independent associated factors of the severity of the disease. However, TyG index was not an independent associated factor of the severity of disease in non-obese men with OSAHS. In addition, SWS and GGT were negatively correlated. SWS combined with serum GGT may be predictive of the severity of the disease. This study may have added to our understanding of the pathogenesis of OSAHS in non-obese men.


Assuntos
Apneia Obstrutiva do Sono , Sono de Ondas Lentas , Humanos , Masculino , Glucose , Obesidade/complicações , Estudos Retrospectivos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/complicações , Síndrome
8.
Sci Rep ; 12(1): 19210, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357475

RESUMO

It is a promising research for optimization of quantum gate in the field of quantum computation. We investigate the feasibility of implementing the single-qubit gate (Hadamard) in molecular rotational system. By applying the Multi-constraint quantum optimal control method, the excepted final states can be achieved based on the molecular rotational states both in resonant and non-resonant cases with the control pulses. The permanent electric dipole moment is ignored in non-resonance. Besides, the zero-pulse area constraint and the constant fluence constraint are employed to optimize shapes of control pulses. Finally, we show that the Hadamard gate can be realized with the high fidelity (0.9999) and also examine the dependence of the fidelity on pulse fluence as well as the control pulse.

9.
Sci Rep ; 12(1): 14918, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050511

RESUMO

Implementation of quantum gates are important for quantum computations in physical system made of polar molecules. We investigate the feasibility of implementing gates based on pendular states of the molecular system by two different quantum optical control methods. Firstly, the Multi-Target optimal control theory and the Multi-Constraint optimal control theory are described for optimizing control fields and accomplish the optimization of quantum gates. Numerical results show that the controlled NOT gate (CNOT) can be realized under the control of above methods with high fidelities (0.975 and 0.999) respectively. In addition, in order to examine the dependence of the fidelity on energy difference in the same molecular system, the SWAP gate in the molecular system is also optimized with high fidelity (0.999) by the Multi-Constraint optimal control theory with the zero-area and constant-fluence constraints.

11.
J Transl Med ; 20(1): 269, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35706031

RESUMO

BACKGROUND: The next generation sequencing (NGS) based non-invasive prenatal test (NIPT) has outplayed the traditional serum biochemical tests (SBT) in screen of fetal aneuploidies with a high sensitivity and specificity. However, it has not been widely used as a primary screen tool due to its high cost and the cheaper SBT is still the choice for primary screen even with well-known shortages in sensitivity and specificity. Here, we report a multiplex droplet digital PCR NIPT (dPCR-NIPT) assay that can detect trisomies 21, 18 and 13 (T21, T18 and T13) in a single tube reaction with a better sensitivity and specificity than the SBT and a much cheaper price than the NGS-NIPT. METHODS: In this study, the dPCR-NIPT assay's non-clinical characteristics were evaluated to verify the cell free fetal DNA (cffDNA) fraction enrichment efficiencies, the target cell free DNA (cfDNA) concentration enrichment, the analytical sensitivity, and the sample quality control on the minimum concentration of cfDNA required for the assay. We validated the clinical performance for this assay by blindly testing 283 clinical maternal plasma samples, including 36 trisomic positive samples, from high risk pregnancies to access its sensitivity and specificity. The cost effectiveness of using the dPCR-NIPT assay as the primary screen tool was also analyzed and compared to that of the existing contingent strategy (CS) using the SBT as the primary screen tool and the strategy of NGS-NIPT as the first-tier screen tool in a simulating situation. RESULTS: For the non-clinical characteristics, the sample processing reagents could enrich the cffDNA fraction by around 2 folds, and the analytical sensitivity showed that the assay was able to detect trisomies at a cffDNA fraction as low as 5% and the extracted cfDNA concentration as low as 0.2 ng/µL. By testing the 283 clinical samples, the dPCR-NIPT assay demonstrated a detection sensitivity of 100% and a specificity of 95.12%. Compared to the existing CS and the NGS-NIPT as the first-tier screen strategy, dPCR-NIPT assay used as a primary screen tool followed by the NGS-NIPT rescreen is the most economical approach to screen pregnant women for fetal aneuploidies without sacrificing the positive detection rate. CONCLUSION: This is the first report on a dPCR-NIPT assay, consisting of all the necessary reagents from sample processing to multiplex dPCR amplification, can detect T21, T18 and T13 in a single tube reaction. The study results reveal that this assay has a sensitivity and specificity superior to the SBT and a cost much lower than the NGS-NIPT. Thus, from both the test performance and the economic benefit points of views, using the dPCR-NIPT assay to replace the SBT as a primary screen tool followed by the NGS-NIPT rescreen would be a better approach than the existing CS for detection of fetal aneuploidies in maternal plasma.


Assuntos
Ácidos Nucleicos Livres , Síndrome de Down , Aneuploidia , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Reação em Cadeia da Polimerase , Gravidez , Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico
12.
Molecules ; 27(10)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35630656

RESUMO

Detecting the characteristic decomposition products (SO2, SOF2, and HF) of SF6 is an effective way to diagnose the electric discharge in SF6-insulated equipment. Based on first-principles calculations, Au, Ag, and Cu were chosen as the surface modification transition metal to improve the adsorption and gas-sensing properties of MoTe2 monolayer towards SO2, SOF2, and HF gases. The results show that Au, Ag, and Cu atoms tend to be trapped by TH sites on the MoTe2 monolayer, and the binding strength increases in the order of Ag < Au < Cu. In gas adsorption, the moderate adsorption energy provides the basis that the TM-MoTe2 monolayer can be used as gas-sensing material for SO2, SOF2, and HF. The conductivity of the adsorption system changes significantly. The conductivity decreases upon gases adsorption on TM-MoTe2 monolayer, except the conductivity of Ag-MoTe2 monolayer increases after interacting with SOF2 gas.

13.
Am J Transl Res ; 14(3): 1778-1787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422929

RESUMO

OBJECTIVE: To analyze the cardiac structure and function of patients with recurrent atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) with echocardiography and to predict the factors affecting recurrence. METHODS: In this retrospective study, 87 patients who received RFCA for AF in the Weihai Municipal Hospital from June 2018 to December 2019 were enrolled. According to the recovery of postoperative sinus rhythm (SR), patients with recovered SR were assigned to the research group (Res group, n=60), while those with AF recurrence were included in the control group (Con group, n=27). The transthoracic echocardiography was adopted to measure the changes of left atrium-related parameters of patients before RFCA and at 6 months after surgery, and the transesophageal three-dimensional echocardiography was adopted for measuring the changes of left atrial appendage (LAA)-related parameters. In addition, multivariate logistic regression was performed to analyze the factors influencing postoperative recurrence of AF. RESULTS: After 6-month follow up, SR was restored in 60 cases and AF recurred in 27 cases. After surgery, the left atrial anteroposterior diameter (LAAPD), left atrial left and right diameter (LALRD), left atrial up and down diameter (LAUDD), maximum volume of left atrium (LAVmax), minimum volume of left atrium (LAVmin), opening diameter of LAA (LAAOD), maximum volume of LAA (LAAVmax), and minimum volume of LAA (LAAV min) of the Res group decreased, and were lower than those of the Con group. In addition, the left atrial ejection fraction (LAEF), vessel function index and dilatation index of the Res group increased significantly postoperatively, and were higher than those of the Con group. The Res group also showed significantly higher LAA area change percentage [LAAAC (%)] and LAA emptying velocity (LAAEV) than the Con group. Moreover, age, history of hypertension, LAVmax and LAAAC (%) were identified to be the independent risk factors for postoperative recurrence of AF. CONCLUSION: Patients with increased left atrial diameter and volume, large LAAOD, and small ejection fraction are more susceptible to AF recurrence, and LAAOD is a predictor of postoperative recurrence of AF.

14.
Front Psychiatry ; 13: 754938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280166

RESUMO

Objective: To present a long-lasting misdiagnosed case of anti-GAD65 autoimmune encephalitis (AE) and promote the early identification of reversible psychotic symptoms in AE. Methods: The case report was generated through detailed assessment of clinical characteristics, cerebral magnetic resonance images, and laboratory results. Meanwhile, a literatures review related to the topic was conducted. Results: Psychotic symptoms could be presented in the early stage of anti-GAD65 autoimmune encephalitis. Even though there exists a transdisciplinary gap that hinder the timely recognition of early psychiatric symptoms as components of organic disease, a few strategies could be introduced to enable the earlier recognition and appropriate treatment. Conclusions: Our report intends to raise awareness to promote the early identification of immune-mediated "symptomatic" forms of psychosis.

16.
Plant Cell ; 34(6): 2343-2363, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35262740

RESUMO

Mitochondrial function depends on the RNA processing of mitochondrial gene transcripts by nucleus-encoded proteins. This posttranscriptional processing involves the large group of nuclear-encoded pentatricopeptide repeat (PPR) proteins. Mitochondrial processes represent a crucial part in animal immunity, but whether mitochondria play similar roles in plants remains unclear. Here, we report the identification of RESISTANCE TO PHYTOPHTHORA PARASITICA 7 (AtRTP7), a P-type PPR protein, in Arabidopsis thaliana and its conserved function in immunity to diverse pathogens across distantly related plant species. RTP7 affects the levels of mitochondrial reactive oxygen species (mROS) by participating in RNA splicing of nad7, which encodes a critical subunit of the mitochondrial respiratory chain Complex I, the largest of the four major components of the mitochondrial oxidative phosphorylation system. The enhanced resistance of rtp7 plants to Phytophthora parasitica is dependent on an elevated mROS burst, but might be independent from the ROS burst associated with plasma membrane-localized NADPH oxidases. Our study reveals the immune function of RTP7 and the defective processing of Complex I subunits in rtp7 plants resulted in enhanced resistance to both biotrophic and necrotrophic pathogens without affecting overall plant development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Imunidade Vegetal/genética , Processamento Pós-Transcricional do RNA , Splicing de RNA , RNA Mitocondrial/metabolismo , Explosão Respiratória
17.
Nature ; 603(7900): 302-308, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35173333

RESUMO

Two forms of associative learning-delay conditioning and trace conditioning-have been widely investigated in humans and higher-order mammals1. In delay conditioning, an unconditioned stimulus (for example, an electric shock) is introduced in the final moments of a conditioned stimulus (for example, a tone), with both ending at the same time. In trace conditioning, a 'trace' interval separates the conditioned stimulus and the unconditioned stimulus. Trace conditioning therefore relies on maintaining a neural representation of the conditioned stimulus after its termination (hence making distraction possible2), to learn the conditioned stimulus-unconditioned stimulus contingency3; this makes it more cognitively demanding than delay conditioning4. Here, by combining virtual-reality behaviour with neurogenetic manipulations and in vivo two-photon brain imaging, we show that visual trace conditioning and delay conditioning in Drosophila mobilize R2 and R4m ring neurons in the ellipsoid body. In trace conditioning, calcium transients during the trace interval show increased oscillations and slower declines over repeated training, and both of these effects are sensitive to distractions. Dopaminergic activity accompanies signal persistence in ring neurons, and this is decreased by distractions solely during trace conditioning. Finally, dopamine D1-like and D2-like receptor signalling in ring neurons have different roles in delay and trace conditioning; dopamine D1-like receptor 1 mediates both forms of conditioning, whereas the dopamine D2-like receptor is involved exclusively in sustaining ring neuron activity during the trace interval of trace conditioning. These observations are similar to those previously reported in mammals during arousal5, prefrontal activation6 and high-level cognitive learning7,8.


Assuntos
Condicionamento Clássico , Drosophila , Animais , Encéfalo/citologia , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Dopamina , Drosophila/anatomia & histologia , Drosophila/citologia , Drosophila/fisiologia , Neurônios , Receptores Dopaminérgicos
18.
Mol Plant Pathol ; 23(4): 530-542, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34935273

RESUMO

Oomycetes represent a unique group of plant pathogens that are phylogenetically distant from true fungi and cause significant crop losses and environmental damage. Understanding of the genetic basis of host plant susceptibility facilitates the development of novel disease resistance strategies. In this study, we report the identification of an Arabidopsis thaliana T-DNA mutant with enhanced resistance to Phytophthora parasitica with an insertion in the Raf-like mitogen-activated protein kinase kinase kinase gene Raf36. We generated additional raf36 mutants by CRISPR/Cas9 technology as well as Raf36 complementation and overexpression transformants, with consistent results of infection assays showing that Raf36 mediates Arabidopsis susceptibility to P. parasitica. Using a virus-induced gene silencing assay, we silenced Raf36 homologous genes in Nicotiana benthamiana and demonstrated by infection assays the conserved immune function of Raf36. Mutagenesis analyses indicated that the kinase activity of Raf36 is important for its immune function and interaction with MKK2, a MAPK kinase. By generating and analysing mkk2 mutants and MKK2 complementation and overexpression transformants, we found that MKK2 is a positive immune regulator in the response to P. parasitica infection. Furthermore, infection assay on mkk2 raf36 double mutant plants indicated that MKK2 is required for the raf36-conferred resistance to P. parasitica. Taken together, we identified a Raf-like kinase Raf36 as a novel plant susceptibility factor that functions upstream of MKK2 and directly targets it to negatively regulate plant resistance to P. parasitica.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Phytophthora , Quinases raf/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Phytophthora/fisiologia , Doenças das Plantas/microbiologia
19.
Ren Fail ; 43(1): 1479-1491, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34723750

RESUMO

BACKGROUND: End-stage renal disease (ESRD) is the final stage during the development of renal failure. Depression is the most common psychiatric disorder in patients with ESRD, which in turn aggravates the progression of renal failure, however, its underlying mechanism remains unclear. This study aimed to reveal the pathogenesis and to discover novel peripheral biomarkers for ESRD patients with depression through metabolomic analysis. METHODS: Ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) was used to explore changes of serum metabolites among healthy controls, ESRD patients with or without depression. The differential metabolites between groups were subjected to clustering analysis, pathway analysis, receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 57 significant serum differential metabolites were identified between ESRD patients with or without depression, which were involved in 19 metabolic pathways, such as energy metabolism, glycerolipid metabolism, and glutamate-centered metabolism. Moreover, the area under the ROC curve of gentisic acid, uric acid, 5-hydroxytryptamine, 2-phosphoglyceric acid, leucyl-phenylalanine, propenyl carnitine, naloxone, pregnenolone, 6-thioxanthene 5'-monophosphate, hydroxyl ansoprazole, zileuton O-glucuronide, cabergoline, PA(34:2), PG(36:1), probucol and their combination was greater than 0.90. CONCLUSIONS: Inflammation, oxidative stress and energy metabolism abnormalities, glycerolipid metabolism, and glutamate-centered metabolism are associated with the pathogenesis of ESRD with depression, which may be promising targets for therapy. Furthermore, the identified differential metabolites may serve as biomarkers for the diagnosis of ESRD patients with depression.


Assuntos
Depressão/complicações , Falência Renal Crônica/sangue , Falência Renal Crônica/metabolismo , Metabolômica/métodos , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Depressão/sangue , Metabolismo Energético , Feminino , Humanos , Inflamação , Falência Renal Crônica/psicologia , Metabolismo dos Lipídeos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Estresse Oxidativo , Curva ROC , Espectrometria de Massas em Tandem/métodos
20.
Exp Ther Med ; 21(6): 622, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33936279

RESUMO

Aberrant expression of microRNAs (miRNAs/miRs) plays a key role in the development of non-small cell lung cancer (NSCLC). In the present study, lower miRNA (miR)-491-5p levels and a higher forkhead box P4 (FOXP4) mRNA level were observed in NSCLC tissues and cell lines, compared to adjacent tissues and the normal human lung epithelial cell line BEAS-2B, respectively. A549 cell proliferation and migration were inhibited upon transfection of miR-491-5p mimics compared to miR-negative control (NC) mimics. In addition, compared to miR-NC mimics, overexpression of miR-491-5p decreased FOXP4 expression, while downregulation of miR-491-5p increased FOXP4 expression in A549 cells. The dual luciferase assay confirmed that the 3'untranslated region of FOXP4 was a target for miR-491-5p in A549 cells. Moreover, compared with the control short hairpin (sh)RNA, there was lower expression levels of TGF-ß and its downstream targets (MMP-2 and MMP-9) in the FOXP4 shRNA group. Similarly, compared to miR-NC mimics, overexpression of miR-491-5p decreased MMP-2 and MMP-9 expression levels. In FOXP4-knockdown A549 cells, overexpression of miR-491-5p showed little effect on cell proliferation/migration. In A549 cells, overexpression of FOXP4 partially reversed the miR-491-5p mimics-induced inhibition on the cell proliferation and migration. These results may provide new insights into the role of miR-491-5p in NSCLC.

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