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Artificial intelligence has surged forward with the advent of generative models, which rely heavily on stochastic computing architectures enhanced by true random number generators with adjustable sampling probabilities. In this study, we develop spin-orbit torque magnetic tunnel junctions (SOT-MTJs), investigating their sigmoid-style switching probability as a function of the driving voltage. This feature proves to be ideally suited for stochastic computing algorithms such as the restricted Boltzmann machines (RBM) prevalent in pretraining processes. We exploit SOT-MTJs as both stochastic samplers and network nodes for RBMs, enabling the implementation of RBM-based neural networks to achieve recognition tasks for both handwritten and spoken digits. Moreover, we further harness the weights derived from the preceding image and speech training processes to facilitate cross-modal learning from speech to image generation. Our results clearly demonstrate that these SOT-MTJs are promising candidates for the development of hardware accelerators tailored for Boltzmann neural networks and other stochastic computing architectures.
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Compared to the bulk heterojunction (BHJ) devices, the quasiplanar heterojunction (Q-PHJ) exhibits a more stable morphology and superior charge transfer performance. To achieve both high efficiency and long-term stability, it is necessary to design new materials for Q-PHJ devices. In this study, QxIC-CF3 and QxIC-CH3 are designed and synthesized for the first time. The trifluoromethylation of the central core exerts a modulatory effect on the molecular stacking pattern, leveraging the strong electrostatic potential and intermolecular interactions. Compared with QxIC-CH3, the single crystal structure reveals that QxIC-CF3 exhibits a more compact 2D linear stacking behavior. These benefits, combined with the separated electron and hole transport channels in Q-PHJ device, lead to increased charge mobility and reduced energy loss. The devices based on D18/QxIC-CF3 exhibit an efficiency of 18.1%, which is the highest power conversion efficiency (PCE) for Q-PHJ to date. Additionally, the thermodynamic stability of the active layer morphology enhances the lifespan of the aforementioned devices under illumination conditions. Specifically, the T80 is 420 h, which is nearly twice that of the renowned Y6-based BHJ device (T80 = 220 h). By combining the advantages of the trifluoromethylation and Q-PHJ device, efficient and stable organic solar cell devices can be constructed.
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Designing new acceptors is critical for intrinsically stretchable organic solar cells (IS-OSCs) with high efficiency and mechanical robustness. However, nearly all stretchable polymer acceptors exhibit limited efficiency and high-performance small molecular acceptors are very brittle. In this regard, we select thienylene-alkane-thienylene (TAT) as the conjugate-break linker and synthesize four dimerized acceptors by the regulation of connecting sites and halogen substitutions. It is found that the connecting sites and halogen substitutions considerably impact the overall electronic structures, aggregation behaviors, and charge transport properties. Benefiting from the optimization of the molecular structure, the dimerized acceptor exhibits rational phase separation within the blend films, which significantly facilitates exciton dissociation while effectively suppressing charge recombination processes. Consequently, FDY-m-TAT-based rigid OSCs render the highest power conversion efficiency (PCE) of 18.07 % among reported acceptors containing conjugate-break linker. Most importantly, FDY-m-TAT-based IS-OSCs achieve high PCE (14.29 %) and remarkable stretchability (crack-onset strain [COS]=18.23 %), significantly surpassing Y6-based counterpart (PCE=12.80 % and COS=8.50 %). To sum up, these findings demonstrate that dimerized acceptors containing conjugate-break linkers have immense potential in developing highly efficient and mechanically robust OSCs.
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The conjugate expansion of nonfullerene acceptors is considered to be a promising approach for improving organic photovoltaic performance because of its function in tuning morphological structure and molecular stacking behavior. In this work, two nonfullerene acceptors are designed and synthesized using a 2D π-conjugate expansion strategy, thus enabling the construction of highly-efficient organic solar cells (OSCs). Compared with YB2B (incorporating dibromophenanthrene on the quinoxaline-fused core), YB2T (incorporating dibromobenzodithiophene on the quinoxaline-fused core) has red-shifted spectral absorption and better charge transport properties. Moreover, the more orderly and tightly intermolecular stacking of YB2T provides the possibility of forming a more suitable phase separation morphology in blend films. Through characterization and analysis, the YB2T-based blend film is found to have higher exciton dissociation efficiency and less charge recombination. Consequently, the power conversion efficiency (PCE) of 17.05% is achieved in YB2T-based binary OSCs, while YB2B-based devices only reached 10.94%. This study demonstrates the significance of the aromatic-ring substitution strategy for regulating the electronic structure and aggregation behavior of 2D nonfullerene acceptors, facilitating the development of devices with superior photovoltaic performance.
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Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.
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Infecções Irruptivas , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
The incidence of ischemic heart disease is 2-3 times higher in diabetic patients. However, the effect of dapagliflozin on ischemia-reperfusion myocardial injury in diabetic rats has not been studied. We examined the effects of dapagliflozin on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Rats were divided into four groups (n = 7 in each group): control, control-dapagliflozin, diabetes, and diabetes-dapagliflozin. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water for 2 months. The hearts were perfused in a Langendorff's apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expressions, creatine kinase MB (CK-MB) and troponin imyocardial enzyme extravasation, and lactate dehydrogenase. The recovery of LVDP and ±dP/dt in diabetic rats was lower than that in controls but near normal after dapagliflozin treatment. Diabetic rats had decreased eNOS expression and increased iNOS expression at baseline and after IR, whereas dapagliflozin normalized these parameters after IR. Compared with controls, cardiac NOx levels were initially lower in diabetic patients but higher after IR. Baseline MDA levels were higher in diabetic rats after IR, whereas cardiac NOx levels decreased after treatment with dapagliflozin. Dapagliflozin protects the diabetic rat heart from ischemia-reperfusion myocardial injury by regulating the expression of eNOS and iNOS and inhibiting cardiac lipid peroxidation.
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Diabetes Mellitus Experimental , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos Wistar , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , IsquemiaRESUMO
Chlorine substitution, as an effective and low-cost modification strategy, has been applied in the design of donor and acceptor structures in organic solar cells. We synthesized a series of chlorinated dimerized acceptors to investigate the effect of chlorine numbers and locations on the photovoltaic properties. The results show that the planarity and morphology of DYV-γ-2Cl are greatly improved due to the appropriate numbers and positions of the substituted chlorine atoms. Therefore, the device based on PM6:DYV-γ-2Cl achieves a superior power conversion efficiency (PCE) of 15.54% among the three oligomeric acceptors with optimized molecular planarity and film morphology. This work demonstrated the positive effect of suitable numbers and the substitution positions of chlorines on the molecular arrangement and photovoltaic properties of the corresponding dimerized acceptors.
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Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.
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Infecções Irruptivas , COVID-19 , Humanos , SARS-CoV-2 , Anticorpos , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Background: A third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown. Methods: The blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay. Results: The results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%). Conclusions: A third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.
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Vacinas contra COVID-19 , COVID-19 , Transplante de Rim , Humanos , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/prevenção & controle , ELISPOT , Imunoglobulina G , SARS-CoV-2 , Imunização Secundária , Vacinas contra COVID-19/imunologiaRESUMO
INTRODUCTION: The microgravity environment of spaceflight leads to a series of changes in the human blood system. The aim of the present study was to examine the influence of simulated microgravity on the differentiation of CD34+ cells and to explore whether transcription factor GATA-1, required for the terminal differentiation of committed erythroid progenitor cells, is involved in this process. METHODS: CD34+ cells were cultured in the simulated microgravity conditions created by a rotary cell-culture system (RCCS). The effects of simulated microgravity on the differentiation and apoptosis of CD34+ cells were analyzed using flow cytometry and propidium iodide (PI) staining, respectively. Expression of GATA-1 mRNA in CD34+ cells was determined by real-time quantitative PCR. RESULTS: In the RCCS group, GlyA+ (glycophorin A) expression was lower and CD33+ expression higher than in the 1-g liquid control group (22.21% +/- 3.02% and 60.05% +/- 3.08%, vs. 52.12% +/- 1.92% and 18.87% +/- 1.41%, respectively). The proportion of differentiated cells in the 1-g methylcellulos e group (Gly+% = 54.39% +/- 2.86%, CD33+% = 21.09% +/- 3.19%) was similar to that in the 1-g liquid control group. As shown by real-time quantitative PCR, the relative expression of GATA-1 mRNA in the RCCS group was only 20% of that in the -g control group. CONCLUSIONSs: The differentiation of CD3+ cells, and especially erythroid differentiation, was inhibited by simulated microgravity by a mechanism that appears to involve the suppression of GATA-1 mRNA expression. The results of this study may be useful in understanding the critical effect of simulated microgravity on the pathogenesis of space anemia.
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Antígenos CD34/metabolismo , Células Precursoras Eritroides/metabolismo , Fator de Transcrição GATA1/metabolismo , Simulação de Ausência de Peso , Adulto , Apoptose , Diferenciação Celular , Células Cultivadas , Células Precursoras Eritroides/citologia , Feminino , Citometria de Fluxo , Fator de Transcrição GATA1/genética , Humanos , Reação em Cadeia da Polimerase , Gravidez , RNA Mensageiro/metabolismo , Coloração e RotulagemRESUMO
OBJECTIVE: To construct the recombinant lentivirus RNAi vector, and to determine whether the lentivirus mediated short hairpin RNA (shRNA) can inhibit the tissue factor (TF) expression in endothelial cells. METHODS: Two short hairpin RNAs targeting to human TF were cloned into pENTRTM/U6 plasmid to obtain an entry clone, and the positive clones were verified by sequencing. A recombination reaction was performed between the pENTR/U6 entry construction and pLenti6/BLOCKiTTM-DEST vector, and then the positive clones were confirmed by sequencing. The 293FT cell line was transfected by the above recombined plasmid and lentivirus packing materials, the culture supernatant was harvested, and the virus titer was determined. RT-PCR and ELISA were used to observe the inhibition of TF gene expression after the lentivirus transduction in human umbilical vein endothelial cells. RESULTS: The shRNA sequences targeting to human TF were cloned into the vectors, and an entry clone and an expression clone were constructed successfully, which were proved by sequence determination. Viral particles were packaged in the 293FT cell line, all virus stocks were collected, and the transfection titer was 5*10(5)/transduced unit. RT-PCR and enzyme linked immunosorbent assay demonstrated that the lentivirus stocks could suppress the TF expression in endothelial cells remarkably. CONCLUSION: Lentivirus RNAi vectors containing human TF gene are successfully constructed, and lentivirus mediated shRNA can inhibit the TF expression in endothelial cells, which may provide a highly effective method for the prevention and treatment of thrombo-embolic diseases.
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Células Endoteliais/metabolismo , Vetores Genéticos/genética , Lentivirus/genética , RNA Interferente Pequeno/genética , Tromboplastina/biossíntese , Sequência de Bases , Regulação para Baixo , Células Endoteliais/citologia , Humanos , Dados de Sequência Molecular , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Tromboplastina/genética , Veias Umbilicais/citologiaRESUMO
It is widely recognized that thrombosis is the major event in the evolution of acute myocardial infarction (AMI) and acute ischemic stroke (AIS). But the contribution of coagulation factors to the development of ischemic arterial diseases is still not clearly established. The goal of this study was to establish the possible relationship between coagulation factors as well as anticoagulant and the onset of AMI and AIS. The study population consisted of 69 patients with AMI and 71 with AIS as well as 50 age-matched healthy volunteers. Compared with the control group, plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activities and both TF and TFPI antigens were significantly higher in the AMI group; plasma TF activity and antigen in AIS group were significantly increased, but the activity and antigen of plasma TFPI were significantly decreased in the AIS group. Plasma FVII coagulation (FVII:C) activity was markedly higher in patients with AIS, but not statistically different to the control in patients with AMI. FVIII coagulation (FVIII:C) activity was remarkably higher in patients with AMI but slightly lower than the control in patients with AIS. In the AMI and AIS groups, prothrombin activity and clottable fibrinogen were significantly higher and plasma antithrombin III activity was remarkably lower than the control. The results suggested that during the onset of AMI and AIS, the initiation of TF pathway would be associated with the thrombotic events and that the blood be in hypercoagulable state. But the changes of FVII:C, TFPI and FVIII:C in AMI are different from those in AIS.
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Coagulação Sanguínea , Trombose Coronária/sangue , Trombose Intracraniana/sangue , Tromboplastina/metabolismo , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologiaRESUMO
OBJECTIVE: To establish the possible relationship between some coagulation factors and the onset of acute cerebral infarction (ACI). METHODS: The study population consisted of 71 patients with ACI confirmed by CT and 50 age-matched healthy volunteers. Blood samples were obtained during the onset period of ACI. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activity in plasma were assayed with the chromogenic assay. Plasma TF and TFPI antigen were measured with enzyme linked immunoadsorbent assay (ELISA). Plasma F VII coagulation activity (F VII: C) and F VIII coagulation activity (F VIII: C) were developed in the one-stage system. Plasma prothrombin (FII) was determined with Ecarin assay. Plasma fibrinogen (Fbg) was measured with thrombin assay. Plasma antithrombin III activity (ATIII) was determined using heparin cofactor activity assay. RESULTS: Compared with the control, plasma TF activity and antigen in patients with ACI were significantly higher (both P<0.05). But plasma TFPI activity and antigen were remarkably lower in the ACI group (both P<0.05). Plasma F VII: C was significantly higher (P<0.01), and F VIII: C was markedly lower (P<0.05). Plasma FII was remarkably higher (P<0.01). Similarly the Fbg was significantly higher in the ACI than that in the control group (P<0.01), whereas ATIII was significantly lower (P<0.01). CONCLUSION: The initiation of TF pathway is contributed to the onset of ACI and the blood is in hypercoagulable state during the early period of ACI.
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Infarto Cerebral/sangue , Tromboplastina/fisiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/análise , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Tromboplastina/análiseRESUMO
OBJECTIVE: To develop a method for extracting cytoskeletons and cytoskeleton-associated proteins for proteomic analysis. METHODS: A subcellular sequential proteome extraction method was exploited. The extraction procedure was optimized and controlled according to observed cell morphology changes and one- and two-dimensional electrophoresis images. The extraction efficiency and selectivity were evaluated by Western blotting and mass spectrometry. RESULTS: Four extracted fractions clearly displayed distinct patterns. Western blotting detected the fraction-marker proteins FAK, integrin-ß1, histone H1 and cytokeratin 19 only in their expected fractions. About 90% of the protein spots in the cytoskeleton fraction were identified by mass spectrometry as cytoskeleton and/or its associated proteins. CONCLUSION: The subcellular proteome sequential fractionation method facilitates the detection of proteins of low abundance and shows a high reproducibility and selectivity, and thus can serve as an ideal pre-fractionation method prior to two-dimensional electrophoresis.
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Citoesqueleto/química , Proteoma/análise , Proteômica/métodos , Eletroforese em Gel Bidimensional/métodos , Humanos , Frações SubcelularesRESUMO
The aim of this study was to assess the relationship between urinary Smad1 and glomerular hyperfiltration (GHF) in type 2 diabetes mellitus (T2DM), and to explore the factors related to the urinary Smad1 in T2DM. The reference value of the estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals. 30 patients with GHF, 58 patients with norm-GFR T2DM, and 24 healthy patients who served as controls were recruited. Urinary Smad1, fasting plasma glucose (FPG), fasting serum C-Peptide (C-P), hemoglobin A1C (HbA1c), cystatin C, and other chemistry laboratory parameters of T2DM participants and controls were measured. Patients with GHF had higher levels of urinary Smad1 than the control group, and those with norm-GFR. For T2DM patients with body mass index, age, and gender adjustments, urinary Smad1 was positively correlated with FPG, HbA1C, and eGFR, but negatively correlated with fasting serum C-P. Multivariate linear regression analysis demonstrated that eGFR, HbA1C, and fasting serum C-P were independently associated with urinary Smad1. High levels of urinary Smad1 were found in GHF patients with T2DM, which may be another potential mechanism of GHF in relation to diabetic nephropathy.
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Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Proteína Smad1/urina , Adulto , Biomarcadores/metabolismo , Glicemia/metabolismo , Peptídeo C/sangue , Estudos de Casos e Controles , Estudos Transversais , Cistatina C/sangue , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
The purpose of this study was to investigate the prevalence of tubular damage in short-term (less than five years) type 2 diabetes mellitus (T2DM) patients and to explore the correlation between tubular markers and their relationship with renal indices at different stages of diabetic nephropathy. A group of 101 short-term T2DM patients and 28 control subjects were recruited. Tubular markers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D: -glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1), as well as urinary albumin excretion were measured in voided urine. Glomerular filtration rate (GFR) was estimated via Macisaac's formula. The patients were further categorized into three groups, namely, the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, according to their urine albumin/creatinine ratio (UACR). Urinary tubular markers were compared and their correlations with renal indices [UACR and estimated GFR (eGFR)] were analyzed among the different diabetic groups. Compared with the control group, Urinary NGAL [median (IQR)][83.6(41.4-138.7) µg/gcr vs. 32.9(26.1-64.5) µg/gcr], NAG [13.5(8.7-17.9) U/gcr vs. 7.6(6.5-13.0) U/gcr] and KIM-1 [120.0(98.4-139.9) ng/gcr vs. 103.1(86.8-106.2) ng/gcr] in the T2DM were all markedly increased. For all patients, urinary NGAL had stronger positive correlations with UACR than NAG (R = 0.556 vs. 0.305, both P < 0.05). In addition, only urinary NGAL showed a negative correlation with eGFR (R = -0.215, P < 0.05). Urinary KIM-1, however, showed no significant difference among the three T2DM groups and did not correlate with either UACR or eGFR. As UACR increased from the normoalbuminuria to the last macroalbuminuria group, all of the markers increased. However, only the concentrations of NGAL were statistically different among the three diabetic groups. The correlation between the tubular markers and their relationships with the renal indices differed markedly among the three T2DM groups. In conclusion, these results suggest that tubular damage is common in short-term T2DM patients. Urinary NGAL may be a promising early marker for monitoring renal impairment in short-term T2DM patients.
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Acetilglucosaminidase/urina , Proteínas de Fase Aguda/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/epidemiologia , Lipocalinas/urina , Glicoproteínas de Membrana/urina , Proteínas Proto-Oncogênicas/urina , Adulto , Idoso , Albuminúria/classificação , Albuminúria/complicações , Albuminúria/epidemiologia , Biomarcadores/urina , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Receptores Virais , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
AIM: To assess whether glomerular hyperfiltration (GHF) could result in renal tubular damage in type 2 diabetes mellitus (T2DM) patients. METHODS: Reference value of estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals based on serum CysC levels. GHF was defined as an eGFR exceeding the sex-specific 97.5th percentile in non-diabetic individuals. In the present study, 30 with GHF, 58 with norm-GFR T2DM, and 24 healthy controls were recruited. Tubular markers, such as urinary N-acetyl-ß-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1), as well as serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), were measured and compared. The correlation of these markers with eGFR was analyzed in the GHF group. RESULTS: The GHF group had higher urinary NGAL and KIM-1 levels but lower serum NGAL level than the norm-GFR and control groups. Slightly decreased serum NGAL and increased urinary NGAL levels were also noted in the norm-GFR group compared with those of the controls. There was no statistical difference in the urinary NAG values among the three groups. Correlation analysis showed that eGFR was positively related to fasting blood glucose (FBG), HbA1c, urinary NGAL, and KIM-1, but negatively with serum NGAL in the GHF group. CONCLUSION: Higher urinary tubular damage markers were found in T2DM patients with GHF than the norm-GFR and control groups, probably a direct proof that GHF is a deleterious factor for diabetic nephropathy.
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Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Túbulos Renais/fisiopatologia , Acetilglucosaminidase/urina , Proteínas de Fase Aguda/urina , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Lipocalina-2 , Lipocalinas/sangue , Lipocalinas/urina , Masculino , Glicoproteínas de Membrana/urina , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/urina , Receptores ViraisRESUMO
To scan differentially expressed genes and to identify candidate molecular markers in nasopharyngeal carcinoma (NPC), we analyzed cDNA microarray data by GenMAPP to find specifically expressed genes in NPC and used tissue microarray and in situ hybridization techniques to confirm our microarray results. Our cDNA microarray results showed that TSPAN-1 and DPP10 genes were down-expressed in NPC, and COX7B and RFC2 genes were over-expressed in NPC. Real-time quantitative reverse transcription-PCR and in situ hybridization (ISH) techniques confirmed that TSPAN-1 and DPP10 genes had only 40.72 and 40.70% positive expression in NPC, but had high positive expression in chronic inflammation of nasopharyngeal mucosa (P < 0.01). However, COX7B and RFC2 genes were high positive rate in NPC (84.24 and 64.53%, respectively) than in normal control tissues. The data suggested that TSPAN-1, DPP10, COX7B and RFC2 genes might be the putative molecular markers of NPC.
Assuntos
Biomarcadores Tumorais/genética , Estudos de Associação Genética/métodos , Hibridização In Situ/métodos , Neoplasias Nasofaríngeas/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Carcinoma , Perfilação da Expressão Gênica/métodos , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnósticoRESUMO
OBJECTIVE: To investigate the effect of simulated microgravity on the proliferation of human monocytic cells THP-1 and the expression of tissue factor (TF) mRNA. METHODS: THP-1 cells were cultured under a simulated microgravity environment using the rotating cell culture system (RCCS). The changes in the cell proliferation after microgravity culture were assessed by cell counting and cell cycle analysis with flow cytometry. RT-PCR was used to detect the changes in the expression of TF mRNA in THP-1 cells. RESULTS: Culture under simulated microgravity resulted in a significant decrease in the cell number of THP-1 cells in comparison with that of the control cells (P<0.01). After a 24-h culture under microgravity, the G0-Gl phase cells increased from the control level of (46.57∓1.64)% to (67.64∓2.71)% (P<0.05). The cells in both groups showed a low level of TF mRNA expression in the absence of LPS stimulation. A 4-h stimulation with LPS caused up-regulated expression of TF mRNA in both cells, but the microgravity group showed a significantly smaller increase in the expression (2.301∓0.179) than the control group (9.210∓1.328) (P<0.05). CONCLUSION: Microgravity can inhibit the proliferation of THP-1 cells and suppress the cellular expression of TF mRNA.
Assuntos
Monócitos/citologia , Monócitos/metabolismo , Tromboplastina/metabolismo , Ausência de Peso , Proliferação de Células , Células Cultivadas , Humanos , RNA Mensageiro/genética , Tromboplastina/genética , Simulação de Ausência de PesoRESUMO
OBJECTIVE: To examine the urinary level of tissue factor (uTF) and its procoagulant activity (PCA) in patients with diabetes mellitus, and explore the relationship between uTF and renal damage in diabetes mellitus. METHODS: Eighty-six patients with type 2 diabetes mellitus were divided into 3 groups according to urine albumin excretion (UACR), namely normal albuminuria group, microalbuminuria group and macroalbuminuria group. The levels of uTF, PCA, blood urea nitrogen (BUN), serum creatinine (CRE), serum cystatin C (CYSC), glycohemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured in all the patients and 21 healthy controls. RESULTS: Compared with normal control, the diabetic patients showed significantly increased levels of uTF and PCA. The urinary TF-PCA was positively correlated to BUN, CYSC, CRE, UACR, fasting glucose and hs-CRP, but not to uTF; only hs-CRP, UACR were positively correlated to uTF. CONCLUSION: uTF is probably implicated in the development and progression of diabetic nephropathy.