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The implementation of photoelectrochemical water purification technology can address prevailing environmental challenges that impede the advancement and prosperity of human society. In this study, Cu, which is abundant on Earth, was fabricated using an electrochemical deposition process, in which the preferential orientation direction and carrier concentration of the Cu-based oxide semiconductor were artificially adjusted by carefully controlling the OH- and applied voltage. In particular, Cu2O grown with a sufficient supply of OH- ions exhibited the (111) preferred orientation, and the (200) surface facet was exposed, independently achieving 90% decomposition efficiency in a methyl orange (MO) solution for 100 min. This specialized method minimizes the recombination loss of electron-hole pairs by increasing the charge separation and transport efficiency of the bulk and surface of the Cu2O multifunctional absorption layer. These discoveries and comprehension not only offer valuable perspectives on mitigating self-photocorrosion in Cu2O absorbing layers but also provide a convenient and expeditious method for the mass production of water purification systems that harness unlimited solar energy. These properties enable significant energy saving and promote high-speed independent removal of organic pollutants (i.e., MO reduction) during the water purification process.
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Background: Hyperkalemia is a frequent and potentially lethal complication of chronic kidney disease (CKD). We retrospectively examined the potassium-lowering effect of oral fludrocortisone and its adverse effects in hyperkalemic CKD patients not yet on dialysis. Methods: Thirty-three patients (23 men and 10 women, ages 69±14 years) were included. To control hyperkalemia at the outpatient clinic, twenty-one patients (Group 1) received fludrocortisone (0.05-0.1 mg/day) without changes in angiotensin II receptor blockers (ARBs) and calcium polystyrene sulfonate (CPS), while twelve patients (Group 2) were treated with fludrocortisone in addition to stopping ARBs and/or adding low-dose CPS. Results: Fludrocortisone was administered for a median of 169 days (interquartile range, 47-445). At the first follow-up after fludrocortisone administration, serum potassium dropped from 6.14±0.32 mEq/L to 4.52±1.06 mEq/L (p<0.001) in Group 1 and from 6.37±0.35 mEq/L to 4.08±0.74 mEq/L (p<0.01) in Group 2. Ten patients in Group 1 and five patients in Group 2 measured serum potassium levels at four outpatient visits before and after fludrocortisone administration, respectively. The frequency of serum potassium ≥6.0 mEq/L decreased from 19/40 (48%) to 2/40 (5%) (p<0.001) in Group 1 and from 11/20 (55%) to 0/20 (0%) (p<0.001) in Group 2. Eleven patients experienced sodium retention-related problems after fludrocortisone administration: 7 with worsening leg edema, 2 with pleural effusions, and 2 with pulmonary edema. Conclusion: In pre-dialysis CKD patients, fludrocortisone at low doses effectively reduced serum potassium levels; however, sodium retention was a common adverse effect.
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PURPOSE: The objective of this study was to assess the feasibility of incorporating virtual reality/augmented reality (VR/AR) programs into practical tests administered as part of the Korean Radiological Technologists Licensing Examination (KRTLE). This evaluation is grounded in a comprehensive survey that targeted enrolled students in departments of radiology across the nation. METHODS: In total, 682 students from radiology departments across the nation were participants in the survey. An online survey platform was used, and the questionnaire was structured into 5 distinct sections and 27 questions. A frequency analysis for each section of the survey was conducted using IBM SPSS ver. 27.0. RESULTS: Direct or indirect exposure to VR/AR content was reported by 67.7% of all respondents. Furthermore, 55.4% of the respondents expressed that VR/AR could be integrated into their classes, which signified a widespread acknowledgment of VR among the students. With regards to the integration of a VR/AR or mixed reality program into the practical tests for purposes of the KRTLE, a substantial amount of the respondents (57.3%) exhibited a positive inclination and recommended its introduction. CONCLUSION: The application of VR/AR programs within practical tests of the KRTLE will be used as an alternative for evaluating clinical examination procedures and validating job skills.
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Realidade Virtual , Humanos , Estudantes , República da CoreiaRESUMO
A disintegrin and metalloprotease 10 (ADAM10) regulates the expression of cell surface receptors such as tumor necrosis factor receptor 1, toll-like receptor 4, and the receptor for advanced glycation end products (RAGE) by cleaving their extracellular regions. To function as a sheddase, ADAM10 should translocate from the intracellular compartments to the cell surface, but the translocation mechanism remains unclear. In this study, we explored the possible role of adenosine monophosphate-activated protein kinase (AMPK) in the induction of ADAM10 shedding activity. In cultured human aortic endothelial cells (HAECs), 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an AMPK activator, boosted ADAM10 cell surface translocation and ectodomain shedding of RAGE. ADAM10 inhibition with GI 254023X and ADAM10 siRNA silencing both prevented AICAR-induced RAGE ectodomain shedding. AICAR increased AMPK phosphorylation as well. Both Compound C-mediated AMPK inhibition and AMPKα1-siRNA-mediated AMPK depletion suppressed AICAR-induced ADAM10 cell surface translocation and RAGE ectodomain shedding. On the other hand, siRNA knockdown of Rab14, a small GTPase that facilitates the intracellular trafficking of transmembrane proteins, prevented AICAR-induced ADAM10 cell surface translocation and RAGE ectodomain shedding. In conclusion, AMPK activation is an obvious inducer of ADAM10 shedding activity. Our findings suggest that AMPK boosts ADAM10 shedding activity in HAECs by promoting Rab14-dependent ADAM10 cell surface translocation.
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Proteínas Quinases Ativadas por AMP , Células Endoteliais , Humanos , Células Endoteliais/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteína ADAM10/metabolismo , Membrana Celular/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/metabolismo , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
OBJECTIVE: Kidney biopsy is essential for the diagnosis and classification of lupus nephritis. Percutaneous biopsy has a risk of bleeding-related complications; however, data on the risk of percutaneous kidney biopsy in patients with systemic lupus erythematosus (SLE) are scarce. In this study, we aimed to investigate the rate of bleeding-related complications and to examine the risk factors for complications of kidney biopsy in patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively reviewed the medical records of patients with SLE who underwent ultrasound-guided percutaneous kidney biopsy between 2002 and 2020 at a tertiary referral center. Minor complications were defined as hematoma and passing hematuria not requiring an intervention. Major complications included bleeding events that required interventions after the biopsy. Statistical analysis with a multivariate logistic regression model was performed. RESULTS: In a total of 277 patients with SLE, the rate of overall bleeding-related complications after kidney biopsy was 19.9% (minor 13.0%; major 6.9%). Among patients with major complications, 84.2% needed blood transfusion alone without embolization or surgery, whereas the remaining three patients needed embolization for bleeding control. Multivariate analysis revealed that thrombocytopenia (odds ratio [OR] 7.186, 95% confidence interval [CI] 2.315-22.300), and low eGFR (OR 3.478, 95% CI 1.094-11.056) were significantly associated with the risk of major bleeding-related complications after kidney biopsy. CONCLUSION: Percutaneous kidney biopsy is accompanied by the risk of bleeding-related complications; however, most events in our study did not require vascular intervention for bleeding control. Low platelet count and low estimated glomerular filtration rate (eGFR) significantly increase the risk of complications after kidney biopsy in patients with SLE. Key Points ⢠The rate of overall bleeding-related complications after kidney biopsy was about 20% of patients with SLE. ⢠The most commonly observed events were gross hematuria followed by blood transfusion. ⢠Thrombocytopenia and poor kidney function areis an important risk of bleeding-related complications after kidney biopsy.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Trombocitopenia , Humanos , Hematúria/etiologia , Estudos Retrospectivos , Rim/patologia , Hemorragia/complicações , Biópsia/efeitos adversos , Biópsia Guiada por Imagem/efeitos adversos , Trombocitopenia/complicaçõesRESUMO
Dual-phasic (DP)-TiO2 -based composites are considered attractive anode materials for high lithium-ion storage because of the synergetic contribution from dual-phases in lithium-ion storage. However, a comprehensive investigation on more efficient architectures and platforms is necessary to develop lithium-storage devices with high-rate capability and long-term stability. Herein, for the first time, a rationally designed bronze-rich DP-TiO2 -embedded amorphous carbon nanoarchitecture, denoted as DP-TiO2 @C, from sacrificial Ti-metal-organic frameworks (Ti-MOFs) via a two-step pyrolysis process is proposed. The bronze/anatase DP-TiO2 @C nanocomposites are successfully synthesized using a unique pyrolysis process, which decomposes individually the metal clusters and organic linkers of Ti-MOFs. DP-TiO2 @C exhibits a significantly high density and even distribution of nanoparticles (<5 nm), enabling the formation of numerous heterointerfaces. Remarkably, the bronze-rich DP-TiO2 @C shows high specific capacities of 638 and 194 mAh g-1 at current densities of 0.1 and 5 A g-1 , respectively, owing to the contribution of the synergetic interfacial structure. In addition, reversible specific capacities are observed at a high rate (5 A g-1 ) during 6000 cycles. Thus, this study presents a new approach for the synthesis of DP-TiO2 @C nanocomposites from a sacrificial Ti-MOF and provides insights into the efficient control of the volume ratio in DP-TiO2 anode architecture.
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We investigated the clinical characteristics, neuroimaging findings, and final diagnosis of patients with acute isolated or prominent dysarthria who visited the emergency department (ED) between 1 January 2020 and 31 December 2021. Of 2028 patients aged ≥ 18 years with neurologic symptoms treated by a neuro-emergency expert, 75 with acute isolated or predominant dysarthria within 1 week were enrolled. Patients were categorized as having isolated dysarthria (n = 28, 37.3%) and prominent dysarthria (n = 47, 62.7%). The causes of stroke were acute ischemic stroke (AIS) (n = 37, 49.3%), transient ischemic attack (TIA) (n = 14, 18.7%), intracerebral hemorrhage (n = 1, 1.3%), and non-stroke causes (n = 23, 30.7%). The most common additional symptoms were gait disturbance or imbalance (n = 8, 15.4%) and dizziness (n = 3, 13.0%) in the stroke and non-stroke groups, respectively. The isolated dysarthria group had a higher rate of TIA (n = 7, 38.9%), single and small lesions (n = 10, 83.3%), and small-vessel occlusion in Trial of Org 101072 in acute stroke treatment (n = 8, 66.7%). Acute isolated or prominent dysarthria in the ED mostly presented as clinical symptoms of AIS, but other non-stroke and medical causes were not uncommon. In acute dysarthria with ischemic stroke, multiple territorial and small and single lesions are considered a cause.
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AIMS: Glucagon-like peptide-1 alleviates the deleterious effects of advanced glycation end products (AGEs), but the underlying mechanisms are not fully understood. In this study, we investigated the protective mechanism using liraglutide, a glucagon-like peptide-1 receptor agonist, in cultured human aortic endothelial cells (HAECs). MAIN METHODS: Following liraglutide treatment in HAECs, the receptor for AGEs (RAGE) was measured in both cell lysate and culture supernatant, the cytosolic free Ca2+ level was monitored using Fluo-4 AM, the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was analyzed, and immunofluorescence staining was used to visualize a disintegrin and metalloprotease 10 (ADAM10) on the cell surface. KEY FINDINGS: Liraglutide (100 nM) induced ectodomain shedding of RAGE within 30 min and inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) induced by AGEs of bovine serum albumin (AGE-BSA). Further experiments revealed that liraglutide rapidly increases extracellular Ca2+ influx through L-type calcium channels and activates AMPK, resulting in the translocation of ADAM10 to the cell surface, whereas siRNA-mediated ADAM10 depletion prevents liraglutide-induced ectodomain shedding of RAGE and eliminates liraglutide's inhibitory effect on AGE-BSA-induced ICAM-1 expression. Moreover, compound C-mediated AMPK inhibition and siRNA-mediated AMPK depletion both prevented ADAM10 translocation to the cell surface and ADAM10-mediated ectodomain shedding of RAGE. SIGNIFICANCE: Liraglutide reduces the number of intact RAGE on the cell surface by inducing ADAM10-mediated ectodomain shedding, which decreases the inflammatory effects of AGEs. AMPK activated by extracellular Ca2+ influx is critically involved in the translocation of ADAM10 to the cell surface, where it cleaves RAGE.
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Aorta , Células Epiteliais , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Liraglutida/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , HumanosRESUMO
The 90 kDa ribosomal S6 kinases (RSKs) are serine threonine kinases comprising four isoforms. The isoforms can have overlapping functions in regulation of migration, invasion, proliferation, survival, and transcription in various cancer types. However, isoform specific differences in RSK1 versus RSK2 functions in gene regulation are not yet defined. Here, we delineate ribosomal S6 kinases isoform-specific transcriptional gene regulation by comparing transcription programs in RSK1 and RSK2 knockout cells using microarray analysis. Microarray analysis revealed significantly different mRNA expression patterns between RSK1 knockout and RSK2 knockout cell lines. Importantly some of these functions have not been previously recognized. Our analysis revealed RSK1 has specific roles in cell adhesion, cell cycle regulation and DNA replication and repair pathways, while RSK2 has specific roles in the immune response and interferon signaling pathways. We further validated that the identified gene sets significantly correlated with mRNA datasets from cancer patients. We examined the functional significance of the identified transcriptional programs using cell assays. In alignment with the microarray analysis, we found that RSK1 modulates the mRNA and protein expression of Fibronectin1, affecting cell adhesion and CDK2, affecting S-phase arrest in the cell cycle, and impairing DNA replication and repair. Under similar conditions, RSK2 showed increased ISG15 transcriptional expression, affecting the immune response pathway and cytokine expression. Collectively, our findings revealed the occurrence of RSK1 and RSK2 specific transcriptional regulation, defining separate functions of these closely related isoforms.
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Endosomal trafficking of cell surface receptors is essential to their function. Integrins are transmembrane receptors that integrate adhesion to the extracellular matrix with engagement of the cytoskeleton. Ligated integrins mediate diverse signals that regulate matrix assembly, cell survival, cell morphology, and cell motility. Endosomal trafficking of integrins modulates these signals and contributes to cell motility and is required for cancer cell invasion. The phosphoprotein PEA-15 modulates integrin activation and ERK MAP Kinase signaling. To elucidate novel PEA-15 functions we utilized an unbiased proteomics approach. We identified several binding partners for PEA-15 in the endosome including clathrin and AP-2 as well as integrin ß1 and other focal adhesion complex proteins. We confirmed these interactions using proximity ligation analysis, immunofluorescence imaging, pull-down and co-immunoprecipitation. We further found that PEA-15 is enriched in endosomes and was required for efficient endosomal internalization of α5ß1 integrin and cellular migration. Importantly, PEA-15 promotion of migration was dependent on PEA-15 phosphorylation at serines 104 and 116. These data support a novel endosomal role for PEA-15 in control of endosomal trafficking of integrins through an association with the ß1 integrin and clathrin complexes, and thereby regulation of cell motility.
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Proteínas Reguladoras de Apoptose/metabolismo , Endocitose/fisiologia , Endossomos/metabolismo , Integrina alfa5beta1/metabolismo , Fosfoproteínas/metabolismo , Proteínas Reguladoras de Apoptose/genética , Adesão Celular , Linhagem Celular Tumoral , Humanos , Espectrometria de Massas , Proteômica/métodosRESUMO
Hematuria, either glomerular or extraglomerular, is defined as 3 or more red blood cells (RBCs)/high power field. Currently, urinalyses are commonly performed using automated urine sediment analyzers. To assess whether RBC counting by automated urine sediment analyzers is reliable for defining hematuria in glomerular disease, random specimen urinalyses of men with nephritic glomerular disease (7674 urinalyses) and bladder cancer (12,510 urinalyses) were retrospectively reviewed. Urine RBCs were counted by an automated urine sediment analyzer based on flow cytometry (UF-1000i, Sysmex Corporation) or digital image analysis (Cobas 6500, Roche Diagnostics GmbH). In about 20% of urine specimens, the specific gravity was less than 1.010, making the RBC counts unreliable. In the urine specimens with specific gravity ≥ 1.010, RBC counts measured using either UF-1000i or Cobas 6500 were well correlated with the positive grades in the dipstick blood test. However, at a trace, 1+, or higher positive dipstick tests for blood, RBC counts were graded significantly lower in glomerular disease than in bladder cancer. The findings suggest that RBC counting by UF-1000i or Cobas 6500 underestimates the severity of hematuria in glomerular disease, possibly because dysmorphic RBCs in glomerular disease are susceptible to hemolysis and/or fail to be properly recognized.
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Hematúria/diagnóstico , Nefropatias/urina , Neoplasias da Bexiga Urinária/urina , Idoso , Estudos de Casos e Controles , Contagem de Eritrócitos , Feminino , Citometria de Fluxo , Humanos , Nefropatias/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/sangueRESUMO
We aimed to evaluate the overall clinical characteristics of patients treated by a neuro-emergency expert dedicated to the emergency department (ED) as an attending neurologist during the COVID-19 pandemic. We included adult patients who visited the ED between 1 January and 31 December 2020 and were treated by a neuro-emergency expert. We retrospectively obtained and analyzed the data on patients' clinical characteristics and outcome. The neuro-emergency expert treated 1155 patients (mean age, 62.9 years). The proportion of aged 18-40 years was the lowest, and the most common modes of arrival were public ambulance (50.6%) and walk-in (42.3%). CT and MRI examinations were performed in 94.4 and 33.1% of cases, respectively. The most frequent complaints were dizziness (31.8%), motor weakness (24.2%), and altered mental status (15.8%). The ED diagnoses were acute ischemic stroke (19.8%), benign paroxysmal positional vertigo (14.2%), vestibular neuritis (9.9%), and seizure (8.8%). The mean length of stay in the ED was 207 min. Of the patients, 55.0% were admitted to the hospital, and 41.8% were discharged for outpatient follow-up. Despite the longer stay and the complexity and difficulty of neurological diseases during the COVID-19 pandemic, the accurate diagnosis and treatment provided by a neuro-emergency expert can be presented as a good model in the ED.
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Isquemia Encefálica , COVID-19 , Acidente Vascular Cerebral , Adulto , Vertigem Posicional Paroxística Benigna , Serviço Hospitalar de Emergência , Humanos , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
A series of gold(I) complexes with the general formula [Au(L2)(L')] (L2=4-phenyl-N-(prop-2-yn-1-yl)quinazoline-2-carboxamide, L'=PPh3 (triphenylphosphine), 1; TPA (1,3,5-triaza-7-phosphaadamantane), 2, and Me2-imy (1,3-dimethylimidazol-2-ylidene), 3) were synthesized and fully characterized by spectroscopic methods. The alkynyl ligand L2 belongs to the quinazoline carboxamide class of ligands that are known to bind to the translocator protein (TSPO) at the outer mitochondrial membrane. 1 and 2 exert cytotoxic effects in bladder cancer cells with IC50 values in the low micromolar range. Further mechanistic analysis indicated that the two complexes both act by inducing reactive oxygen species and caspase-mediated apoptosis. The complexes inhibit thioredoxin reductase, an established target of anticancer gold(I) complexes. Docking studies confirmed that after ligand exchange the free ligand L2 can interact with the TSPO binding site.
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OBJECTIVE: Recent studies have suggested that deep-learning models can satisfactorily assist in fracture diagnosis. We aimed to evaluate the performance of two of such models in wrist fracture detection. METHODS: We collected image data of patients who visited with wrist trauma at the emergency department. A dataset extracted from January 2018 to May 2020 was split into training (90%) and test (10%) datasets, and two types of convolutional neural networks (i.e., DenseNet-161 and ResNet-152) were trained to detect wrist fractures. Gradient-weighted class activation mapping was used to highlight the regions of radiograph scans that contributed to the decision of the model. Performance of the convolutional neural network models was evaluated using the area under the receiver operating characteristic curve. RESULTS: For model training, we used 4,551 radiographs from 798 patients and 4,443 radiographs from 1,481 patients with and without fractures, respectively. The remaining 10% (300 radiographs from 100 patients with fractures and 690 radiographs from 230 patients without fractures) was used as a test dataset. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DenseNet-161 and ResNet-152 in the test dataset were 90.3%, 90.3%, 80.3%, 95.6%, and 90.3% and 88.6%, 88.4%, 76.9%, 94.7%, and 88.5%, respectively. The area under the receiver operating characteristic curves of DenseNet-161 and ResNet-152 for wrist fracture detection were 0.962 and 0.947, respectively. CONCLUSION: We demonstrated that DenseNet-161 and ResNet-152 models could help detect wrist fractures in the emergency room with satisfactory performance.
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OBJECTIVE: This study aimed to clarify the relative prognostic value of each History, Electrocardiography, Age, Risk Factors, and Troponin (HEART) score component for major adverse cardiac events (MACE) within 3 months and validate the modified HEART (mHEART) score. METHODS: This study evaluated the HEART score components for patients with chest symptoms visiting the emergency department from November 19, 2018 to November 19, 2019. All components were evaluated using logistic regression analysis and the scores for HEART, mHEART, and Thrombolysis in Myocardial Infarction (TIMI) were determined using the receiver operating characteristics curve. RESULTS: The patients were divided into a derivation (809 patients) and a validation group (298 patients). In multivariate analysis, age did not show statistical significance in the detection of MACE within 3 months and the mHEART score was calculated after omitting the age component. The areas under the receiver operating characteristics curves for HEART, mHEART and TIMI scores in the prediction of MACE within 3 months were 0.88, 0.91, and 0.83, respectively, in the derivation group; and 0.88, 0.91, and 0.81, respectively, in the validation group. When the cutoff value for each scoring system was determined for the maintenance of a negative predictive value for a MACE rate >99%, the mHEART score showed the highest sensitivity, specificity, positive predictive value, and negative predictive value (97.4%, 54.2%, 23.7%, and 99.3%, respectively). CONCLUSION: Our study showed that the mHEART score better detects short-term MACE in high-risk patients and ensures the safe disposition of low-risk patients than the HEART and TIMI scores.
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Ras mutations are present in only a subset of sporadic human cutaneous squamous cell carcinomas (cSCC) even though Ras is activated in most. This suggests that other mechanisms of Ras activation play a role in the disease. The aberrant expression of RasGRP1, a guanyl nucleotide exchange factor for Ras, is critical for mouse cSCC development through its ability to increase Ras activity. However, the role of RasGRP1 in human keratinocyte carcinogenesis remains unknown. Here we report that RasGRP1 is significantly elevated in human cSCC and that high RasGRP1 expression in human primary keratinocytes triggered activation of endogenous Ras and significant morphological changes including cytoplasmic vacuole formation and growth arrest. Moreover, RasGRP1-expressing cells were autophagic as indicated by LC3-II increase and the formation of LC3 punctae. In an in vitro organotypic skin model, wild type keratinocytes generated a well-stratified epithelium, while RasGRP1-expressing cells failed to do so. Finally, RasGRP1 induced transformation-like changes in skin cells from Li-Fraumeni patients with inactivating p53 mutations, demonstrating the oncogenic potential of this protein. These results support a role for RasGRP1 in human epidermal keratinocyte carcinogenesis and might serve as an important new therapeutic target.
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BACKGROUND: Glycosuria is one of the manifestations of acute tubulointerstitial nephritis (ATIN), but may also be observed in other renal diseases. In this study, we investigated the value of non-diabetic glycosuria as a diagnostic clue for ATIN. METHODS: We retrospectively reviewed the medical records of adult patients who underwent a kidney biopsy as an evaluation for serum creatinine > 1.4 mg/dL. Patients with proteinuria in the nephrotic range, diabetes mellitus, or transplanted kidney were excluded. The laboratory abnormalities suggestive of tubular injury were compared between 28 patients (14 men and 14 women, mean age 48.5 ± 14.1 years) with ATIN and 116 patients (76 men and 40 women, mean age 53.1 ± 15.0 years) with other diagnoses. RESULTS: In ATIN, glycosuria (≥ 1+ on dipstick; 68%) was more frequent than hypophosphatemia (18%), hypouricemia (18%), hypokalemia (18%), and tubular proteinuria (40%). In other diagnoses, glycosuria (≥ 1+) was detected in 7 (6%) patients; 6 of them had the histological diagnosis of antineutrophil cytoplasmic antibody-associated glomerulonephritis. The presence of glycosuria (≥ 1+) had 68% sensitivity and 94% specificity for ATIN, with the positive likelihood ratio of 11.24 and the negative likelihood ratio of 0.34. Pyuria and low total CO2 were equally and more sensitive (68% and 71%, respectively) than glycosuria (≥ 1+), but had no diagnostic value due to low specificities (58% and 60%, respectively). CONCLUSION: In non-diabetic, non-nephrotic patients undergoing a kidney biopsy for azotemia, 1+ or higher glycosuria, if present, was a good predictor of the diagnosis of ATIN.
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Azotemia/etiologia , Glicosúria/etiologia , Rim/patologia , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/urina , Adulto , Idoso , Biópsia , Creatinina/sangue , Feminino , Humanos , Hipopotassemia/etiologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/sangue , Nefrite Intersticial/patologia , Proteinúria/etiologia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Effective pharmacological treatments for patients with advanced clear cell renal carcinoma (ccRCC) are limited. Bimetallic titanium-gold containing compounds exhibit significant cytotoxicity against ccRCC in vitro and in vivo and inhibit invasion and angiogenisis in vitro and markers driving these phenomena. However, in vivo preclinical evaluations of such compounds have not examined their pharmacokinetics, pathology, and hematology. Here we use NOD.CB17-Prkdc SCID/J mice bearing xenograft ccRCC Caki-1 tumors to evaluate the in vivo efficacies of two titanium-gold compounds Titanocref and Titanofin (based on auranofin analogue scaffolds) accompanied by pharmacokinetic and pathology studies. A therapeutic trial was performed over 21 days at 5 mg/kg/72h of Titanocref and 10 mg/kg/72h of Titanofin tracking changes in tumor size. We observed a significant reduction of 51% and 60%, respectively (p < 0.01) in tumor size in the Titanocref- and Titanofin-treated mice compared to the starting size, while the vehicle-treated mice exhibited a tumor size increase of 138% (p < 0.01). Importantly, no signs of pathological complication as a result of treatment were found. In addition, Titanocref and Titanofin treatment reduced angiogenesis by 38% and 54%, respectively. Microarray and qRT-PCR analysis of ccRCC Caki-1 cells treated with Titanocref revealed that the compound alters apoptosis, JNK MAP kinase, and ROS pathways within 3 h of treatment. We further show activation of apoptosis by Titanocref and Titanofin in vivo by caspase 3 assay. Titanocref is active against additional kidney cancer cells. Titanocref and Titanofin are therefore promising candidates for further evaluation toward clinical application in the treatment of ccRCC.
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An 8 ton/day solid refuse fuel gasification process with air oxidant was operated under various conditions to generate electricity. Solid refuse fuels with fluff type feedstock were fabricated from municipal solid wastes. The tested experimental conditions included feedstock charging rate into the gasifier, equivalence ratio, and oxygen enrichment; varying these conditions resulted in different gasification characteristics, such as cold gas efficiency and carbon conversion ratio. Optimum conditions were a charging rate of 50 to 60% by volume (504.71 to 605.65 kg/Sm2) of feedstock in the gasifier, equivalence ratio of 0.21 to 0.33, and no oxygen enrichment. Average cold gas efficiency and carbon conversion ratio were 71.30% and 72.07%, respectively, at optimum conditions. Pollutants such as dust, tar, and gases, were analyzed at the outlet of the cleaning facility and gasifier, and their low concentrations in the producer gas were sufficient to allow for operation of the gas engine. The gasification process exhibited stable operation over 288 h, which included the facility check period. The average gasifier temperature was 825 °C, 17.14% by volume of producer gas was syngas, and gas engine power generation was 235 kWh during this period; power consumption of the entire system was 68 kWh. These results demonstrate that the gasification process for converting solid waste to energy can be operated at a commercial scale.