HNRNPA2B1 stabilizes NFATC3 levels to potentiate its combined actions with FOSL1 to mediate vasculogenic mimicry in GBM cells.

BACKGROUND: Vasculogenic mimicry (VM) is an enigmatic physiological feature that influences blood supply within glioblastoma (GBM) tumors for their sustained growth. Previous studies identify NFATC3, FOSL1 and HNRNPA2B1 as significant mediators of VEGFR2, a key player in vasculogenesis, and their molecular relationships may be crucial for VM in GBM. AIMS: The aim of this study was to understand how NFATC3, FOSL1 and HNRNPA2B1 collectively influence VM in GBM. METHODS: We have investigated the underlying gene regulatory mechanisms for VM in GBM cell lines U251 and U373 in vitro and in vivo. In vitro cell-based assays were performed to explore the role of NFATC3, FOSL1 and HNRNPA2B1 in GBM cell proliferation, VM and migration, in the context of RNA interference (RNAi)-mediated knockdown alongside corresponding controls. Western blotting and qRT-PCR assays were used to examine VEGFR2 expression levels. CO-IP was employed to detect protein-protein interactions, ChIP was used to detect DNA-protein complexes, and RIP was used to detect RNA-protein complexes. Histochemical staining was used to detect VM tube formation in vivo. RESULTS: Focusing on NFATC3, FOSL1 and HNRNPA2B1, we found each was significantly upregulated in GBM and positively correlated with VM-like cellular behaviors in U251 and U373 cell lines. Knockdown of NFATC3, FOSL1 or HNRNPA2B1 each resulted in decreased levels of VEGFR2, a key growth factor gene that drives VM, as well as the inhibition of proliferation, cell migration and extracorporeal VM activity. Chromatin immunoprecipitation (ChIP) studies and luciferase reporter gene assays revealed that NFATC3 binds to the promoter region of VEGFR2 to enhance VEGFR2 gene expression. Notably, FOSL1 interacts with NFATC3 as a co-factor to potentiate the DNA-binding capacity of NFATC3, resulting in enhanced VM-like cellular behaviors. Also, level of NFATC3 protein in cells was enhanced through HNRNPA2B1 binding of NFATC3 mRNA. Furthermore, RNAi-mediated silencing of NFATC3, FOSL1 and HNRNPA2B1 in GBM cells reduced their capacity for tumor formation and VM-like behaviors in vivo. CONCLUSION: Taken together, our findings identify NFATC3 as an important mediator of GBM tumor growth through its molecular and epistatic interactions with HNRNPA2B1 and FOSL1 to influence VEGFR2 expression and VM-like cellular behaviors.

Extrapolation study for determining the time since injury in a rat subcutaneous hematoma model utilizing ATR-FTIR spectroscopy.

The determination of the time of an injury has been a major problem in forensic science due to the lack of objective, reliable and portable methods. In this study, a subcutaneous hemorrhage model in rats was established over six days, and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy coupled with chemometrics was used to determine the time since injury. Initial principal component analysis (PCA) showed variance among hematoma sites. Subsequently, spectral data were acquired to establish a dependable partial least square (PLS) regression model with predictive abilities. The root mean square error of cross-validation (RMSECV) and the root mean square error of prediction (RMSEP) values produced by a genetic algorithm (GA) were 0.64 d (R2 = 0.88) and 0.57 d (R2 = 0.90), respectively. Few variables were involved in the model, and significantly better results were obtained in comparison to the conventional full-spectrum PLS model. In combination with the results of variable importance in projection (VIP) scores, all components, including proteins, nucleic acids and phospholipids, provided inferences regarding the samples at different time points; additionally, amide I and II bands represented the secondary structure of proteins and provided the largest contribution. Based on our preliminary study, the combination of swift and nondamaging ATR-FTIR spectroscopy with chemometrics could prove to be an advantageous approach for gauging the age of an injury in the forensic field.

Facile synthesis of nitrogen-doped carbon dots for ultrasensitive detection of anticancer drug gefitinib based on IFE.

Gefitinib, a highly significant antitumor drug, is now commonly employed in clinical settings as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer, colon cancer, and breast cancer. Herein, a convenient, rapid, and accurate fluorescence method based on nitrogen-doped carbon dots (NCDs) was designed for ultrasensitive detection of gefitinib. The NCDs were easily synthesized through one-pot hydrothermal process using p-phenylenediamine and D-glutamic acid as the precursors. The sensing strategy relied on the fluorescence of NCDs at 345 nm, which was selectively reduced by gefitinib based on the inner filter effect (IFE). With a broad linear range of 0.025-30 µg/mL and a low limit of detection of 5.5 ng/mL, the probe was successfully applied to the detection of gefitinib in human serum samples, demonstrating strong practicality, affordability, and high accuracy. The proposed sensor is simple in design, fast in detection and cost-effective, and exhibits promising application in drug real-time analysis.

Examining the utility and accuracy of the interRAI Emergency Department Screener in identifying high-risk older emergency department patients: A Canadian multiprovince prospective cohort study.

Objectives: We set out to determine the accuracy of the interRAI Emergency Department (ED) Screener in predicting the need for detailed geriatric assessment in the ED. Our secondary objective was to determine the discriminative ability of the interRAI ED Screener for predicting the odds of discharge home and extended ED length of stay (>24 hours). Methods: We conducted a multiprovince prospective cohort study in Canada. The need for detailed geriatric assessment was determined using the interRAI ED Screener and the interRAI ED Contact Assessment as the reference standard. A score of ≥5 was used to classify high-risk patients. Assessments were conducted by emergency and research nurses. We calculated the sensitivity, positive predictive value, and false discovery rate of the interRAI ED Screener. We employed logistic regression to predict ED outcomes while adjusting for age, sex, academic status, and the province of care. Results: A total of 5629 older ED patients across 11 ED sites were evaluated using the interRAI ED Screener and 1061 were evaluated with the interRAI ED Contact Assessment. Approximately one-third of patients were discharged home or experienced an extended ED length of stay. The interRAI ED Screener had a sensitivity of 93%, a positive predictive value of 82%, and a false discovery rate of 18%. The interRAI ED Screener predicted discharge home and extended ED length of stay with fair accuracy. Conclusion: The interRAI ED Screener is able to accurately and rapidly identify individuals with medical complexity. The interRAI ED Screener predicts patient-important health outcomes in older ED patients, highlighting its value for vulnerability screening.

How carbon trading policy should be integrated with carbon tax policy-laboratory evidence from a model of the current state of carbon pricing policy in China.

China is planning to introduce carbon tax policy to control the carbon emissions of the country better and achieve the "3060 goals", but there is still widespread discussion about how to introduce it and how to combine it with cap and trade. China has already established a national carbon emission trading market; however, there is also disagreement on whether to impose the carbon tax on companies and projects that have been included in scope of cap and trade. This paper adopts the research method of experimental economics to study the effect on social economy and social emission reduction under cap and trade, carbon tax, and carbon tax-carbon trading policies, and analyzes average prices of carbon market under cap and trade and carbon tax-carbon trading policies. The study finds that under the carbon tax-carbon trading policy, carbon emissions cannot be reduced significantly; but the profits of manufacturers will be reduced significantly; meanwhile, this reduction effect is even more severe for high consumption manufacturers; and it will be resulting in a lower average carbon market price under the carbon tax-carbon trading policies than under the cap and trade policy. This paper will provide theoretical suggestions for introducing carbon tax policy into China in the future and make policy recommendations for the better development of China's carbon market.

Fluorescent lanthanide metal-organic framework for rapid and ultrasensitive detection of methcathinone in human urine.

Methcathinone (MC), a new and easily abused psychoactive substance, not only has a rigorous impact on public security, but also endangers people's health. Herein, novel fluorescent europium metal-organic frameworks (Eu-MOF) were synthesized through a facile one-step solvothermal strategy and utilized as an effective "signal-off" sensing platform for rapid and ultrasensitive detection of MC. The as-fabricated Eu-MOF possessed superior optical properties encompassing bright red fluorescence and good photostability. In the presence of MC, the fluorescence of Eu-MOF was significantly quenched, mainly attributing to the internal filtering effect between Eu-MOF and MC. The fluorescent signal showed high selectivity for MC over other illicit drugs, and offered two linear ranges of 1-100 ng/mL and 100-4000 ng/mL with a detection limit of 0.40 ng/mL. Strikingly, the nanoprobe could be applied for the assay of MC in human urine with satisfactory recoveries and acceptable results. This work provides a promising route for MC detection to effectively control illicit drug pandemic worldwide.

Performance of nitrogen removal in an alternating activated sludge reactor for full-scale applications.

A novel wastewater treatment process, known as an alternating activated sludge reactor (AASR), is proposed to treat wastewater in full-scale operations. The AASR is a technical development based on the sequencing batch reactor (SBR) and cyclic activated sludge technology (CAST). The performance of AASR was evaluated in this study and found to be effective for the removal of pollutants. The average effluent NH4+-N, TN, TP, and COD concentrations were 0.5, 17, 0.8, and 40 mgL-1, respectively. The corresponding average removal efficiencies were 97%, 59%, 83%, and 83%, respectively, indicating that the AASR was also a successful operating system for the removal of organic matter. The AASR has many advantages, such as successive filling, high removal efficiency, high stability and reliability, low area requirement, no sludge circulation reflux, and low construction costs. The operation mode of the alternating anoxic, anaerobic, and aerobic conditions displayed a higher efficiency for nitrification than that of conventional SBR. The effective mode for denitrification was a step-feed. The control program of the AASR is highly flexible and can easily be modified by a plant manager to meet various loading requirements.

Association between management of metabolic syndrome and progression of early-stage chronic kidney disease: an observational cohort study.

OBJECTIVES: To analyze the effect of treating metabolic syndrome (MetS) on further kidney function decline in patients with early-stage chronic kidney disease (CKD). METHODS: In a study period of 24 months, 162 patients with early stage CKD were enrolled. Baseline and follow-up data related to the occurrence of MetS and glomerular filtration rate (GFR) were assessed. Subjects were classified into controlled MetS (group 1) and uncontrolled MetS (group 2). Furthermore, they were subdivided into four subgroups: (A) controlled MetS at baseline and at follow-up, (B) uncontrolled MetS at baseline but controlled MetS at follow-up visits, (C) controlled MetS at baseline but uncontrolled MetS at follow-up visits, and (D) uncontrolled MetS at baseline and follow-up visits. RESULTS: Final GFR was lower in group 2 versus group 1 (69.21 ± 20.20 vs. 82.86 ± 22.33 mL/min/1.73 m(2), p <0.001). The presence of MetS had high risk to develop late-stage CKD (HR = 3.279, 95% CI: 1.545-6.958, p = 0.002). Moreover, subgroup D (HR = 2.982, 95% CI: 1.287-6.908, p = 0.011) and the presence of three (p = 0.026) or four (p = 0.049) metabolic components had high risk to develop late-stage CKD. CONCLUSION: Treating MetS slows CKD progression in patients with early-stage of CKD.

MS2 bacteriophage reduction and microbial communities in biosand filters.

This study evaluated the role of physical and biological filter characteristics on the reduction of MS2 bacteriophage in biosand filters (BSFs). Three full-scale concrete Version 10 BSFs, each with a 55 cm sand media depth and a 12 L charge volume, reached 4 log10 reduction of MS2 within 43 days of operation. A consistently high reduction of MS2 between 4 log10 and 7 log10 was demonstrated for up to 294 days. Further examining one of the filters revealed that an average of 2.8 log10 reduction of MS2 was achieved within the first 5 cm of the filter, and cumulative virus reduction reached an average of 5.6 log10 after 240 days. Core sand samples from this filter were taken for protein, carbohydrate, and genomic extraction. Higher reduction of MS2 in the top 5 cm of the sand media (0.56 log10 reduction per cm vs 0.06 log10 reduction per cm for the rest of the filter depth) coincided with greater diversity of microbial communities and increased concentrations of carbohydrates. In the upper layers, "Candidatus Nitrosopumilus maritimus" and "Ca. Nitrospira defluvii" were found as dominant populations, while significant amounts of Thiobacillus-related OTUs were detected in the lower layers. Proteolytic bacterial populations such as the classes Sphingobacteria and Clostridia were observed over the entire filter depth. Thus, this study provides the first insight into microbial community structures that may play a role in MS2 reduction in BSF ecosystems. Overall, besides media ripening and physical reduction mechanisms such as filter depth and long residence time (45 min vs 24 ± 8.5 h), the establishment of chemolithotrophs and proteolytic bacteria could greatly enhance the reduction of MS2.

Thrombotic microangiopathy complicating newly diagnosed Sjögren's syndrome in a dialysis patient.

Thrombotic microangiopathy (TMA) is rarely associated with Sjögren's syndrome (SS). This is the first documented case of a patient undergoing chronic hemodialysis with SS who developed TMA. TMA is an infrequent, life-threatening multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. It is important to make a quick diagnosis of TMA to cure the reported case as early as possible. The patients with TMA should be diagnosed quickly, and in this case plasma exchange and corticosteroids in combination with cyclophosphamide have been associated with a recurrence free period. Cyclophosphamide has led to the development of treatment protocols using alternative immunosuppressive agents in patients with SS showing a poor response to plasmapheresis and potentially life-threatening manifestations. Further research is required to ascertain the sensitivity, specificity, efficacy, timing, cost-benefit ratio, and necessity of cyclophosphamide in the setting of TMA complicating SS.

Roles of singlet oxygen and triplet excited state of dissolved organic matter formed by different organic matters in bacteriophage MS2 inactivation.

Inactivation of bacteriophage MS2 by reactive oxygen species (ROS) and triplet excited state of dissolved organic matter ((3)DOM*) produced by irradiation of natural and synthetic sensitizers with simulated sunlight of wavelengths greater than 320 nm was investigated. Natural sensitizers included purified DOM isolates obtained from wastewater and river waters, and water samples collected from Singapore River, Stamford Canal, and Marina Bay Reservoir in Singapore. Linear correlations were found between MS2 inactivation rate constants (kobs) and the photo-induced reaction rate constants of 2,4,6-trimethylphenol (TMP), a probe compound shown to react mainly with (3)DOM*. Linear correlations between MS2 kobs and singlet oxygen ((1)O2) concentrations were also found for both purified DOM isolates and natural water samples. These correlations, along with data from quenching experiments and experiments with synthetic sensitizers, Rose Bengal (RB), 3'-methoxyacetophenone (3'-MAP), and nitrite [Formula: see text] , suggest that (1)O2, (3)DOM*, and hydroxyl radicals ((•)OH) could inactivate bacteriophage MS2. Linear correlations between MS2 kobs and Specific Ultraviolet Absorption determined at 254 nm (SUVA254) were also found for both purified DOM isolates and natural samples. These results suggest the potential use of TMP as a chemical probe and SUVA254 as an indicator for virus inactivation in natural and purified DOM water samples.