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The demand for a high-performance position sensitive detector (PSD), a novel type of photoelectric sensor, is increasing due to advancements in digitization and automation technology. Cadmium sulfide (CdS), a non-centrosymmetric material, holds significant potential in photoelectric devices. However, the pyroelectric effect of CdS in PSDs and its influence on lateral photoresponse are still unknown. In this work, we fabricated an ITO/CdS/Si heterojunction using chemical bath deposition (CBD) and investigated the pyro-phototronic effect under nonuniform illumination. The theory of electron-hole pairs' generation, separation, and carrier diffusion was carefully considered to understand the underlying mechanisms. Our experimental findings revealed that the device exhibited an exceptionally high position sensitivity (PS) of 1061.3 mV/mm, surpassing the generally observed PS of 655.1 mV/mm induced by single photovoltaic effect by 160.5%. Meanwhile, the PSD demonstrated rapid response times of 0.01 and 0.04 ms, respectively. Moreover, the influence of ambient temperature and electrode distance on the pyro-phototronic effect was well analyzed. Notably, the PSD exhibited remarkable stability even at ambient temperatures up to 150 °C. Despite the considerable working distance of 11 mm, the PS of the PSD remained at 128.99 mV/mm. These findings provide valuable theoretical and experimental foundations for optimizing the design and implementation of high-performance large working distance PSDs.
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BACKGROUND: Serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population, its association with ASCVD incidence in Chinese maintenance hemodialysis (MHD) patients remains unclear. We aimed to evaluate the relationship between Lp(a) levels and ASCVD incidence among MHD patients in Beijing, China. METHODS: This retrospective, observational cohort study included MHD patients at Beijing Tongren Hospital from January 1, 2013 to December 1, 2020, and followed until December 1,2023. The primary outcome was ASCVD occurrence. Kaplan-Meier survival analysis was used to evaluate ASCVD-free survival in MHD patients, with stratification based on Lp(a) levels. Cox regression analyses were conducted to assess the association between Lp(a) levels and the occurrence of ASCVD. RESULTS: A total of 265 patients were enrolled in the study. The median follow-up period were 71 months.78 (29.4%) participants experienced ASCVD events, and 118 (47%) patients died, with 58 (49.1%) deaths attributed to ASCVD. Spearman rank correlation analyses revealed positive correlations between serum Lp(a) levels and LDL-c levels, and negative correlations with hemoglobin, triglyceride, serum iron, serum creatinine, and albumin levels. Multivariate Cox regression analysis showed that Lp(a) levels ≥ 30 mg/L, increased age, decreased serum albumin levels, and a history of diabetes mellitus were significantly associated with ASCVD incidence. CONCLUSIONS: This study demonstrated an independent and positive association between serum Lp(a) levels and the risk of ASCVD in MHD patients, suggesting that serum Lp(a) could potentially serve as a clinical biomarker for estimating ASCVD risk in this population.
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Aterosclerose , Lipoproteína(a) , Diálise Renal , Humanos , Masculino , Feminino , Estudos Retrospectivos , Lipoproteína(a)/sangue , Pessoa de Meia-Idade , Aterosclerose/sangue , Aterosclerose/epidemiologia , Idoso , Pequim/epidemiologia , Fatores de Risco , Incidência , Estudos de CoortesRESUMO
A triple-amplified and ratiometric electrochemical aptasensor for CA125 was designed based on hemin-graphene/SH-ß-cyclodextrin@PdPt nanoflower (H-Gr/SH-ß-CD@PdPtNF) composites and an exonuclease I (Exo I)-assisted strategy. In the nanocomposite, hemin acts as an internal reference signal owing to the reversible heminox/heminred pair. PdPtNFs can significantly improve the electron transfer rate. SH-ß-CD can efficiently enrich quercetin probes through host-guest recognition and increase the second indicator signal. In the presence of CA125, due to the specific binding between the aptamer and CA125, the conformational change of dsDNA (designed by the CA125 aptamer and its complementary DNA) results in the release of quercetin embedded in dsDNA. Subsequently, the free quercetin and DNA fragments are enriched on the H-Gr/SH-ß-CD@PdPtNF-modified electrode. Thus, an enhanced oxidation peak from quercetin (IQ) and a reduced peak from hemin (Ihemin) can indicate the same biological identification event. In addition, the recycling amplification of CA125 by Exo I can effectively assist the increase of the quercetin signal. The value of IQ/Ihemin is linear with the concentration of CA125 in the range from 6.0 × 10-4 to 1.0 × 103 ng/mL, and the limit of detection is 1.4 × 10-4 ng/mL. The recovery of CA125 in human blood serum samples was from 99.2 to 104.4%. The proposed sensor is sensitive and reliable, which provides an avenue for the development of triple amplification and ratiometric signal strategies for detecting tumor markers in clinical diagnostics.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Antígeno Ca-125 , Humanos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Hemina , Limite de Detecção , Quercetina , Antígeno Ca-125/análiseRESUMO
High-load carbonaceous and dust aerosols can significantly reduce direct radiation (DIRR), which would affect photosynthesis in terrestrial ecosystems, thereby further affecting the productivity of vegetation. Based on this, a variety of remote sensing data were used to study the spatiotemporal distributions and changing tendencies of the absorbing aerosols, CO, DIRR, and gross primary productivity (GPP) in China during 2005-2019; then, the relationships were analyzed between different types of absorbing aerosols and DIRR as well as GPP. The results showed that the annual mean absorbing aerosols index (AAI) in China during 2005-2019 was 0.39, with a slow growth rate of 0.02 year-1, and the emission of CO showed a decreasing trend with each passing year, especially in North China Plain and Sichuan Basin. Carbonaceous and dust aerosols were predominantly bounded by Hu line. The east of Hu line was the dominant area of carbonaceous aerosols, and the west of Hu line was the topographical region of dust aerosols. Near the Hu line was the dominant area of carbonaceous-dust aerosols. However, the Karamay-Urumqi-Hami area and Northeast China Plain were exceptional. During the vegetation growing season, different types of absorbing aerosols significantly negatively affected GPP. From a perspective of regional scale variation pattern, the negative effect of absorbing aerosols on vegetation productivity was the most significant in Northeast China; from the perspective of the effects of different vegetation types, the negative effect of absorbing aerosols on grasslands was greater than that of woodlands; from the perspective of the composition characteristics of aerosols, the negative effect of dust aerosols on GPP was greater than that of carbonaceous aerosols.
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Ecossistema , Monitoramento Ambiental , Aerossóis , China , PoeiraRESUMO
An electrochemical aptasensor is described for the detection of prostate specific antigen (PSA). The aptasensor is based on the use of hemin-functionalized graphene-conjugated palladium nanoparticles (H-Gr/PdNPs) deposited on a glassy carbon electrode. The nanocomposites integrate the high electrical conductivity of graphene with the easily functionalized surface chemistry of PdNPs and their excellent catalytic property. The hemin placed on graphene acts as both a protective agent and an in-situ redox probe. The PdNPs provide numerous binding sites for the immobilization of DNA-biotin via coordinative binding between Pd and amino groups. A sensitive and specific PSA assay was attained by immobilizing the PSA aptamer via biotin-streptavidin interaction. The resulting aptasensor has a linear response that covers the PSA concentration range from 0.025 to 205 ng·mL-1, with a 8 pg·mL-1 lower detection limit (at -0.362 V, scan rate: 0.1 mV·s-1, S/N = 3). The method was applied to the quantitation of PSA in spiked serum samples, giving recoveries ranging from 95.0 to 100.3%. Graphical abstract A signal amplified and approving electrochemical aptasensor was constructed for the determination of prostate specific antigen (PSA) based on the use of hemin-functionalized graphene conjugated to palladium nanoparticles (H-Gr/PdNPs). The sensor has a wide linear range, a relatively low detection limit, satisfying stability and high specificity.
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In this work, a novel electrochemical aptasensor was developed for sensitive and selective detection of myoglobin based on meso-tetra (4-carboxyphenyl) porphyrin-functionalized graphene-conjugated gold nanoparticles (TCPP-Gr/AuNPs). Due to its good electric conductivity, large specific surface area, and excellent mechanical properties, TCPP-Gr/AuNPs can act as an enhanced material for the electrochemical detection of myoglobin. Meanwhile, it provides an effective matrix for immobilizing myoglobin-binding aptamer (MbBA). The electrochemical aptasensor has a sensitive response to myoglobin in a linear range from 2.0 × 10-11 M to 7.7 × 10-7 M with a detection limit of 6.7 × 10-12 M (S/N = 3). Furthermore, the method has the merits of high sensitivity, low price, and high specificity. Our work will supply new horizons for the diagnostic applications of graphene-based materials in biomedicine and biosensors.
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Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province.Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dyslipidemia, cardiovascular and cerebrovascular diseases, kidney diseases, and overweight condition, as well as those with an estimated glomerular filtration rate (eGFR)<60 ml/(min·1.73 m2), apparently healthy subjects (1168) were selected. Urine albumin was measured by using the immunoturbidimetic method, serum creatinine was measured by using Jaffe's kinetic method on a morning spot-urine sample, and ACR was calculated. The 95th percentile of ACR in the healthy subjects was used as the normal upper limit.Results The normal upper limit of ACR was 28.71 mg/g (3.25 mg/mmol) for males and 31.85 mg/g (3.60 mg/mmol) for females. Based on this ACR reference value, the age-gender standardized prevalence of albuminuria in the rural areas of Hebei province was 12.9%.Conclusion The ACR reference value in the rural of Hebei province is higher than that of the Western population.
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Albuminas/análise , Creatinina/análise , Adulto , Albuminúria , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias , MasculinoRESUMO
An electron transport layer (ETL) with a suitable gradient energy level can enhance electron transfer, suppress carrier recombination, and effectively improve the photoresponse of photodetectors (PDs). In this letter, a series of ITO/ZnO/CdS/MAPbI3/Spiro-OMeTAD heterojunction PDs were prepared by incorporating a ZnO layer at the CdS/ITO interface upon varying the thickness from 0 to 95 nm. The optimized band arrangement in the PD results in an excellent self-powering ability and improved photoresponse. Moreover, both the photovoltaic and pyroelectric responses strongly correlate with the thickness of the ZnO layer. The PD with an optimal ZnO thin film thickness of 50 nm achieves a huge responsivity (R) of 1.19 × 104 V/W and detectivity (D) of 2.22 × 109 Jones, primarily due to the strengthened pyro-phototronic effects enabled by the dual ETL layers. In addition, the enhanced pyroelectric effect broadens the spectral range of the PD to 360-1550 nm, largely surpassing the band gap of the heterojunction.
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CdS, with a noncentrosymmetric structure, is thought as an important electron transport layer (ETL) in perovskite-based devices, but its pyroelectric effect, which can efficiently modulate the optoelectronic processes, is not well explored. In this work, a MAPbI3 heterojunction of CdS/MAPbI3/Spiro-OMeTAD with a c-axis preferred oxygen-doped CdS ETL is developed as a high-performance photodetector (PD). This PD exhibits a stable self-powered property in the spectral range of â¼360-780 nm due to its excellent photovoltaic effect. Moreover, the light-induced pyroelectric potential in the CdS ETL is demonstrated to be an efficient approach for improving the photoresponses, and different effects are observed for different laser irradiations, which can be well understood from their working mechanisms. Upon 450 nm laser irradiation, the photovoltage responsivity (R) is greatly improved from 596.9 to 6383.6 V/W with an increment of 1069.54%. In addition, the response spectrum is also extended outside the bandgap restriction of the MAPbI3 to 1550 nm due to both the pyroelectric and photothermoelectric effects, which is a big breakthrough for the perovskite heterojunction PD. Through turning the external bias voltage and ambient temperature, the coupling mechanisms of the pyroelectric and photovoltaic effects are further analyzed. This work provides an important understanding of designing the CdS ETL-based perovskite heterojunction for broadband high-performance photoelectric devices by introducing the pyroelectric effect.
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Relationship between plant community functional diversity and ecosystem multifunctionality (EMF) was a new area of ecological research in recent years. Previous studies had mostly focused on the relationship between plant community functional diversity and individual ecosystem function, and lack of understanding of the EMF. In this study, six functional indices of aboveground biomass, soil organic carbon, soil total nitrogen, soil total phosphorus, soil available nitrogen and soil available phosphorus of Gannan alpine meadow were selected to analyze the relationship between plant community functional diversity and EMF on the altitude gradient of Gannan alpine mea-dow by using Bartlett sphericity test and multi-threshold method. The results showed that there was significant altitudinal difference in plant community composition, with species richness and plant coverage at 3500 m were significantly higher than those at other altitudes. Single and multi-functional diversity decreased with the increases of altitude, with significant difference among altitudes. Redundancy analysis showed that single and multi-functional richness, functional evenness and Rao's quadratic entropy were significantly positively correlated with soil temperature, soil water content and soil bulk density, and significantly negatively correlated with soil pH and soil conductivity. In a large threshold range (6%-89%), functional diversity had a significant positive effect on EMF. Based on correlation analysis, optimal regression model and random forest model, it was found that multi-functional richness index had a significant positive relationship with EMF, and that multi-functional richness was also the main driving factor of EMF. Overall, functional richness had the most significant impact on the EMF of alpine meadow in the Qinghai-Tibet Plateau.
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Altitude , Ecossistema , Carbono , China , Pradaria , Nitrogênio/análise , Fósforo , Plantas , Solo/química , TibetRESUMO
OBJECTIVE: To investigate the effects of rapamycin on cholesterol homeostasis and secretory function of 3T3-L1 cells. METHODS: The in vitro cultured 3T3-L1 cells (preadipocytes) were divided into control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group. Intracellular cholesterol level was measured by oil red O staining and high performance liquid chromatography. The secretion levels of leptin and adiponectin were assayed by enzyme-linked immunosorbent assay. The mRNA and protein expressions of peroxisome proliferator-activated receptor (PPARgamma) were assayed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: Oil red O staining showed rapamycin down-regulated 3T3-L1 cells differentiation and lipid accumulation. Quantitative measurement of cholesterol with high performance liquid chromatography showed that the concentrations of free cholesterol in rapamycin treatment groups had a significant reduction. The concentrations of free cholesterol in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (12.89 +/- 0.16), (9.84 +/- 0.45), (9.39 +/- 0.46), and (8.61 +/- 0.34) mg/ml, respectively (P < 0.05), and the concentrations of total cholesterol were (12.91 +/- 0.50), (9.94 +/- 0.96), (10.45 +/- 2.51), and (9.53 +/- 0.63) mg/ml, respectively. The leptin concentrations in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (19.02 +/- 0.52), (16.98 +/- 0.11), (15.62 +/- 0.01), and (13.84 +/- 0.66) ng/ml, respectively. The mRNA expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were significantly lower than that in control group (P < 0.05). The protein expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were 80%, 74%, and 61% of that in control group (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the mRNA expression of PPARgamma was (0.60 +/- 0.14), (0.67 +/- 0.03), and (1.30 +/- 0.14) of that in control group (P < 0.05). The protein expression showed a similar trend with mRNA expression (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the expression of leptin in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group was (19.02 +/- 0.52), (15.62 +/- 0.10), and (14.45 +/- 1.01) and (18.07 +/- 0.66) ng/ml, respectively (P < 0.05 compared with the control group). CONCLUSIONS: By downregulating the expression of PPARgamma, rapamycin can decrease cholesterol accumulation in 3T3-L1 cells and inhibit its leptin-secreting capability. This finding may provide a possible explanation for rapamycin-induced hyperlipidemia in clinical practice.
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Adipócitos/metabolismo , Colesterol/metabolismo , Leptina/metabolismo , PPAR gama/metabolismo , Sirolimo/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Camundongos , PPAR gama/genéticaRESUMO
Air quality has gradually improved in many parts of China; however, air pollution is become more severe in the Fenwei Plain. Using OMI/Aura OMAERUV L2 and PM2.5 data, spatial autocorrelation analysis and back trajectory modeling were used to explore the spatio-temporal patterns of absorptive aerosols over the Fenwei Plain, and the dominant types, transmission paths, and potential source areas were identified. The main results can be summarized as follows:â Annual mean absorbing aerosol index (AAI) values increased between 2005 and 2019, with high period occurring in 2006, 2013, and 2017, with values exceeding 0.63. Xi'an and Linfen were identified as a 'high-high' cluster, with AAI showing poor spatial stability and a 15.3% increase in area over the past 15 years. In contrast, the area connecting Xi'an and Linfen, which occupies 24.2% of the total area of the region, was identified as a 'low-low' cluster, with a sharp drop of 6.2% in area; â¡ The Fenwei Plain has high AAI values across a large area in winter, exceeding 0.8 in Linfen and Xi'an, and 91.5% of the study area exceeding 0.6. Values were lower in spring (AAI>0.4) and autumn (AAI>0.3), with the lowest values occurring in summer. The atmospheric diffusion conditions in spring, autumn, and winter are poor, associated with anticyclonic high-pressure events. The observed high AAI values were significantly affected by atmospheric diffusion conditions, temperature, and precipitation; ⢠Back trajectory and source contribution modeling showed that long-range transport of air masses from Xi'an and Linfen occurs from the northwest, and short-range transport air masses occurs from the east and south. Two long-range sand and dust source areas were determined (with northwestern and northern wind sources); two carbon source areas were identified (with eastern and southern wind sources); and one combined sand and carbon source area was identified (from the Loess Plateau). Of these sources, the northwestern wind source, the Loess Plateau, and the southern wind source have significant influence in Xi'an, and the eastern wind source and the Loess Plateau have a significant impact on Linfen. Linfen is little affected by the northwestern wind source and the dust from the northern wind source. Based on the spatial distribution of CO and its correlation with AAI, it is concluded that cardon in the dominant absorbent aerosol in Linfen dust and carbon are most important in Xi'an.
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A dual signal and label-free electrochemical aptasensor for mucin 1 was constructed based on hemin/graphene@PdPtNPs nanocomposite (H-Gr@PdPtNPs). Hemin attached on the graphene surface not only improves the solubility of graphene and acts as an in-situ electrochemical probe but also exhibits excellent peroxidase-like properties to electrocatalyze the reduction of H2O2. PdPtNPs also show outstanding catalytic capacity to the reduction of H2O2 and provide numerous binding sites for loading dDNA (mucin 1 aptamer and cDNA) to form the sensing interface. In the presence of mucin 1, due to the specific affinity between aptamer and mucin 1, double helix would be induced dissociation and the aptamer would be pulled off from the electrode. As a result, the electrochemical signals of hemin and H2O2 were recovered. Based on these properties, the label-free and sensitive dual signal electrochemical biosensor for mucin 1 detection has been developed. The one is differential pulse voltammetry (DPV) signal of hemin and the other is chronoamperometry signal arisen from the catalytic reduction of H2O2. The linear ranges for mucin 1 were 8.0 pg mL-1 to 80 ng mL-1 and 0.8 pg mL-1 to 80 ng mL-1 with the limit of detection 2.5 pg mL-1 and 0.25 pg mL-1 by DPV and chronoamperometry, respectively. The recovery of mucin 1 in human blood serum samples was from 95.0% to 104.2%. The detection platform does not need signal labeling which greatly reduced the sophisticated and expensive procedures. The aptasensor provide a promising strategy for the determination of mucin 1 in clinical diagnostics.
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Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1-, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.
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OBJECTIVE: To investigate the effects of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanisms. METHODS: Intracellular cholesterol accumulation was measured by Oil Red O staining and high performance liquid chromatography. The effects of rapamycin on interleukin-1 beta (IL-1 beta)-induced mRNA and protein changes of low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1) were assayed by quantitative real-time PCR and Western blot. Transient expressions of 3 types of mammalian target of rapamycin (mTOR), including mTOR-WT (wild type), mTOR-RR (rapamycin resistant, with kinase activity), and mTOR-RR-KD (rapamycin resistant, without kinase activity), were obtained by plasmid transfection. RESULTS: Rapamycin had no significant influence on intracellular cholesterol concentration under normal condition, but it significantly decreased the intracellular cholesterol concentration in the presence of IL-1 beta. Rapamycin dose-dependently suppressed the increased expression of LDLR induced by IL-1 beta and up-regulated the suppressed expression of ABCA1 caused by IL-1 beta. Transient expression of 3 types of mTOR all reduced ABCA1 mRNA expression significantly, which all could be overroded by rapamycin. CONCLUSIONS: Rapamycin may contribute to the maintaining of glomerular mesangial cell intracellular cholesterol homeostasis under inflammatory state by both reducing cholesterol uptake and increasing cholesterol efflux. And the effect may be not completely mediated by mTOR.
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Colesterol/metabolismo , Homeostase/efeitos dos fármacos , Imunossupressores/farmacologia , Interleucina-1beta/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Sirolimo/farmacologia , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular , Humanos , Células Mesangiais/citologia , Receptores de LDL/genética , Receptores de LDL/metabolismo , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: Chronic kidney disease (CKD) is characterized by progressive loss of renal functions. At present, there are only limited therapeutic strategies to slow down the progress of CKD and there is an urgent need to develop new therapeutic strategies to treat CKD patients. Numerous research evidence supports the potential role of EGCG in the renal protection of CKD. However, the clinical use is still limited due to the poor oral bioavailability. The aim of this study was to develop pH-sensitive polymeric nanoparticles of EGCG to improve this deficiency. MATERIALS AND METHODS: EGCG-loaded nanoparticles (EGCG NPs) were prepared by an improved emulsion evaporation method. The formulation prepared was in spherical with uniform sizes, high encapsulation efficiencies and drug loading. The therapeutic efficacy of EGCG NPs on chronic kidney disease was investigated on model of rat Nephrotic syndrome by measuring urinary protein excretion and kidney pathology score. RESULTS: The mean particle size was found to be 91.3±0.8 nm and the encapsulation efficiency% and drug loading% of the formulation were 80.8%±1.6% and 6.3%±1.4%, respectively. The powder X-ray diffraction and differential scanning calorimetry of EGCG NPs showed that EGCG existed in amorphous form in NPs. The release of EGCG from NPs exhibited the lower burst release at pH 1.2 (<10%) and with the increase of pH value, the release of EGCG also gradually increased. During the observation period (24 hours), the total release amount was almost 68%. EGCG NPs could significantly modify the pharmacokinetic profile and increase the bioavailability of EGCG by more than 2.4-fold in comparison with the EGCG powder group. At the end of the fourth and sixth week, proteinuria excretion of nephrotic syndrome rats treated with EGCG NPs was significantly lower than those treated with EGCG powder, and kidney pathology scores in EGCG NPs treated rats were also significantly lower than EGCG powder treated rats. CONCLUSION: The results of pharmacodynamics showed that compared with EGCG powder treatment group, EGCG NPs treatment group had better efficacy and reduce kidney damage.
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Catequina/análogos & derivados , Portadores de Fármacos , Rim/efeitos dos fármacos , Nanopartículas , Síndrome Nefrótica/tratamento farmacológico , Polímeros/química , Fármacos Renais/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Catequina/administração & dosagem , Catequina/química , Catequina/farmacocinética , Cristalografia por Raios X , Modelos Animais de Doenças , Composição de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Rim/patologia , Rim/fisiopatologia , Microscopia Eletrônica de Transmissão , Síndrome Nefrótica/patologia , Síndrome Nefrótica/fisiopatologia , Síndrome Nefrótica/urina , Difração de Pó , Proteinúria/fisiopatologia , Proteinúria/prevenção & controle , Proteinúria/urina , Ratos Sprague-Dawley , Fármacos Renais/química , Fármacos Renais/farmacocinética , SolubilidadeRESUMO
We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052µM and 0.25±0.028µM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1. As in SUP-B15, givinostat induced apoptosis in both cell lines but showed different levels of cleavage of the procaspase proteins Casp-3, Casp-7 and PARP. Levels of cell cycle-DNA repair regulator p21, CHK1 and FANCD2 levels were markedly affected by givinostat treatment. These data further enrich our understanding of the mechanisms of the antineoplastic effects of givinostat in B-ALL and provide a preclinical rationale for the inclusion of givinostat or similar agent in leukemia therapy.
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Apoptose/efeitos dos fármacos , Carbamatos/farmacologia , Proteínas de Fusão bcr-abl , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Carbamatos/uso terapêutico , Caspases/efeitos dos fármacos , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Histona Desacetilases , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologiaRESUMO
BACKGROUND: Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods. RESULTS: Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAFV600E mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAFV600E , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs. CONCLUSIONS: In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAFV600E mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Córtex Cerebral/patologia , Mutação/genética , Neoplasias Neuroepiteliomatosas/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Córtex Cerebral/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Neuroepiteliomatosas/genética , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
The paired-domain-containing Pax transcription factors play an important role in the development of a range of organ, tissue and cell types. Although DNA binding elements and target genes for Pax proteins have been identified, how these proteins identify appropriate DNA elements and regulate different genes in different cellular contexts is not well understood. To investigate the relationship between Pax proteins and their targets, we have studied the in vivo and in vitro properties associated with wild-type and different mutant variants of the Caenorhabditis elegans Pax protein EGL-38. Here, we characterize the properties of four mutations that result in an amino acid substitution in the DNA binding domain of EGL-38. We find that animals bearing the different mutant alleles exhibit tissue-preferential defects in egl-38 function. The mutant proteins are also altered in their activity in an ectopic expression assay and in their in vitro DNA binding properties. Using in vitro selection, we have identified binding sites for EGL-38. However, we show that selected sites function poorly in vivo as EGL-38 response elements, indicating that sequence features in addition to DNA binding determine the efficacy of Pax response elements. The distinction between DNA binding and activity is consistent with the model that other factors commonly play a role in mediating Pax protein target site selection and function in vivo.
Assuntos
Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , DNA/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Dados de Sequência Molecular , Mutação/genética , Alinhamento de Sequência , Fatores de Transcrição/genéticaRESUMO
The objective of the study is to develop a facile and highly sensitive solid phase microextraction-gas chromatography/mass spectrometry method for the analysis of volatile organic compounds in human exhaled breath vapor. For the purpose, a highly ordered nanoporous anodic alumina coating was prepared by a two-step anodic oxidization method based on aluminum substrate. To have a good knowledge of the fiber, some features were characterized and the results indicate that the coating has several advantages, including excellent chemical and thermal stability, high mechanical strength, large surface area and good extraction performance. In addition, some parameters related to extraction efficiency were also studied. Under the optimal conditions, the coating was used to quantitatively extract volatile organic compounds. Good linearity and wide linear range were obtained with correlation coefficients (R(2)) ranging from 0.9933 to 0.9999. The detection limits of benzene homologues, aldehydes and ketones were between 0.7 and 3.4 ng L(-1). Relative standard deviations (n=5) ranged from 1.8 to 15.0%. Satisfied recovery (89-115%) was obtained at two spiked concentration levels. Finally, the developed method was successfully applied for the analysis of volatile organic compounds in human exhaled vapor samples of lung cancer patients and the controls, and the results were statistically analyzed with Independent-Sample T Test. The proposed method exhibits some outstanding merits, including convenience, non-invasion, low cost and sensitivity. It provides a potential tool for rapid detection of volatile organic compounds in human exhaled breath.