Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

Resourcefulness Among Initial Ischemic Stroke Patients: A Longitudinal Study of 12 Months.

Objective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness. Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (±1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories. Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2=6.805, P=0.009), education (x2=44.865, P=0.000), monthly income (x2=13.063, P=0.001), NIHSS scores (x2=44.730, P=0.000), mRS scores (x2=51.788, P=0.000), Hcy (x2=9.345, P=0.002), GSES (x2=56.933, P=0.000), FAD-GF (x2=41.305, P=0.000) and SSRS (x2=52.373, P=0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness. Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.

Influence of anthropogenic activities and loess dusts on the rainwater hydrochemistry in the Chinese Loess Plateau.

Rainwater hydrochemistry is an important indicator for tracing anthropogenic input on air quality. As the fastest economically developing city in the northwestern China and the Chinese Loess Plateau, rainwater chemistry, sources of dissolved solutes, and the influence of loess dust on rainwater chemistry in Xi'an city is unclear. Inorganic ions, δD and δ18O of two years' rainwater samples were measured to decipher the above issues. Rainwater samples were weakly alkaline (pH = 7.2) with the mean total dissolved solids (TDS) values of 43 mg/L. NH4+ and Ca2+ dominated in the cations and SO42- and NO3- dominated in the anions. The wet deposition of sulfur (S) and nitrogen (N) was 70.9 ± 67 mg·(m2·month)-1 and 244.8 ± 270.9 mg·(m2·month)-1, respectively. The meteoric water line in Xi'an was δD = 7.29δ18O+3.72 (R2 = 0.99). δD, δ18O, and d-excess analysis indicated the influence of evaporation on the dissolved solutes in rainwater, especially in the dry season. Rainwater acidity in the Xi'an city was mainly neutralized by Ca2+ and NH4+, and the neutralization ability in Xi'an city is higher than the southern China cities. Correlation analysis (CA), positive matrix factorization (PMF), and the backward air masses trajectory model identified high NH4+ and Ca2+ in rainwater were mainly originated from local agricultural activities and loess dust, while NO3- and SO42- were associated with local coal combustion and vehicle exhaust sources. High inputs of dusts and coal combustion in spring and winter resulted in elevated values of pH and major ions in Xi'an. Due to the air pollution control policy, air quality in Xi'an is getting better in recent years. Our study highlights the influence of anthropogenic activities and loess dusts on the rainwater hydrochemistry in Xi'an and provides important dataset for air pollution control for other cities in semi-arid and arid regions.

KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors.

KRAS mutations are broadly recognized as promising targets for tumor therapy. T cell receptors (TCRs) can specifically recognize KRAS mutant neoantigens presented by human lymphocyte antigen (HLA) and mediate T cell responses to eliminate tumor cells. In the present study, we identify two TCRs specific for the 9-mer KRAS-G12V mutant neoantigen in the context of HLA-A*11:01. The TCR-T cells are constructed and display cytokine secretion and cytotoxicity upon co-culturing with varied tumor cells expressing the KRAS-G12V mutation. Moreover, 1-2C TCR-T cells show anti-tumor activity in preclinical models in female mice. The 9-mer KRAS-G12V mutant peptide exhibits a distinct conformation from the 9-mer wildtype peptide and its 10-mer counterparts. Specific recognition of the G12V mutant by TCR depends both on distinct conformation from wildtype peptide and on direct interaction with residues from TCRs. Our study reveals the mechanisms of presentation and TCR recognition of KRAS-G12V mutant peptide and describes TCRs with therapeutic potency for tumor immunotherapy.

Development and psychometric appraisal of Head Nurse Research Leadership Scale.

AIM: To develop a Head Nurse Research Leadership Scale and evaluate its reliability and validity. DESIGN: A psychometric instrument validation study was conducted in two phases. METHODS: The item tool was generated based on a literature review, semi-structured interview and brainstorming. Twenty experts validated the content of the initial version for two rounds. Thirty-nine clinical nurses conducted the HNRLS-v3 to test the readability of the items in pilot study I. Items were screened based on the critical ratio, correlation coefficient analysis, Cronbach's α coefficient and factor analysis using the data collected from 265 nurses in pilot study II. A cross-sectional survey was conducted in six hospitals to evaluate the reliability and validity between 4 January 2022 and 15 January 2022. Three hundred and sixteen nurses participated in this survey, and 60 completed the questionnaire to validate the test-retest reliability between 1 February and 6 February. RESULTS: A 15-item Head Nurse Research Leadership Scale based on 5 dimensions was developed, and the content validity was satisfied. The 15 items accounted for 77.9% of the variance. Confirmatory factor analysis showed acceptable convergent validity and discriminant validity. The Cronbach's α coefficient, split-half reliability and test-retest reliability of the scale were 0.966, 0.9633 and 0.927, respectively.

Nursing adherence, barriers and facilitators to conduct post-stroke dysphagia screening and assessment: A study based on theoretical domain framework.

BACKGROUND: There are an increasing number of evidence-based recommendations for managing dysphagia in post-stroke patients. However, it is unclear whether nurses adopt these recommendations in their daily nursing practices. AIMS: This study aimed to explore nurses' adherence, barriers, facilitators and views on dysphagia screening and assessment of post-stroke dysphagia. METHODS: In this study, multiple methods were adopted. In Phase 1, a general information questionnaire and a knowledge-attitude-practice and barriers/facilitators questionnaire for dysphagia screening and assessment were distributed in 55 hospitals online. In Phase 2, semi-structured interviews were conducted to explore nurses' views on barriers. Descriptive and one-way variance analyses were used to analyse the quantitative data, while content analysis was used to analyse the qualitative data. This study adheres to STROBE and COREQ guidelines. RESULTS: Nine hundred and forty-two completed questionnaires were collected. Only 36.52% of the nurses screened for swallow function in patients as a guideline. The biggest barrier was 'memory, attention and decision process', with an average score of 3.22 (.74). The different stages of implementation had various types and degrees of barriers (p < .001). Five themes were extracted after interviews, namely 'Inadequate environment and resource support', 'Increased workload', 'Professional value perception', 'Organisational culture', and 'Poor knowledge and skill'. CONCLUSIONS: Nurses' practice of dysphagia screening and assessment of patients with dysphagia after stroke were inadequate, and the barriers originated from patients, leadership and the nurses themselves. RELEVANCE TO CLINICAL PRACTICE: This research extracted five barriers of guidance adherence for post-stroke dysphagia screening and assessment and identified the different kinds and degrees of barriers in five implementation stages, providing a basis for nursing managers to break through the bottleneck of guideline implementation. PATIENT OR PUBLIC CONTRIBUTION: The nurses recruited in this study completed validated questionnaires in the survey and suggestive answers in interviews.

Molecular Basis for the Recognition of HIV Nef138-8 Epitope by a Pair of Human Public T Cell Receptors.

Cross-recognized public TCRs against HIV epitopes have been proposed to be important for the control of AIDS disease progression and HIV variants. The overlapping Nef138-8 and Nef138-10 peptides from the HIV Nef protein are HLA-A24-restricted immunodominant T cell epitopes, and an HIV mutant strain with a Y139F substitution in Nef protein can result in immune escape and is widespread in Japan. Here, we identified a pair of public TCRs specific to the HLA-A24-restricted Nef-138-8 epitope using PBMCs from White and Japanese patients, respectively, namely TD08 and H25-11. The gene use of the variable domain for TD08 and H25-11 is TRAV8-3, TRAJ10 for the α-chain and TRBV7-9, TRBD1*01, TRBJ2-5 for the ß-chain. Both TCRs can recognize wild-type and Y2F-mutated Nef138-8 epitopes. We further determined three complex structures, including TD08/HLA-A24-Nef138-8, H25-11/HLA-A24-Nef138-8, and TD08/HLA-A24-Nef138-8 (2F). Then, we revealed the molecular basis of the public TCR binding to the peptide HLA, which mostly relies on the interaction between the TCR and HLA and can tolerate the mutation in the Nef138-8 peptide. These findings promote the molecular understanding of T cell immunity against HIV epitopes and provide an important basis for the engineering of TCRs to develop T cell-based immunotherapy against HIV infection.

Rhizobium cremeum sp. nov., isolated from sewage and capable of acquisition of heavy metal and aromatic compounds resistance genes.

Two strains of Rhizobia isolated from sewage collected from the Chinese Baijiu distillery were characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains W15T and W16 were grouped as a separate clade closely related to Rhizobium daejeonense L61T (98.6%). Multilocus sequence analysis (MLSA) with three housekeeping genes (recA, glnII and rpoA) also showed that strains W15T and W16 belonged to the genus Rhizobium. Average nucleotide identity and digital DNA-DNA hybridization values between genome sequences of strain W15T and the closely related species ranged from 77.0% to 87.8% and from 23.9% to 30.9%. The DNA G + C content of strain W15T was 61.6 mol%. Strain W15T contained Q-10 as the major ubiquinone and the dominant fatty acids were summed feature 8 (C 18:1ω7c and/or C 18:1ω6c; 73.1%) and C18:0 (7.6%). The main polar lipids are phosphatidylcholine, phosphatidylmethylethanolamine, phosphatidylethanolamine and phosphatidylglycerol. On the basis of the evidences presented in this study, strains W15T and W16 represents a novel species of the genus Rhizobium, for which the name Rhizobium cremeum sp. nov. is proposed. The type strain is W15T (= CGMCC 1.18731T = KACC 22344T).

Spatial distribution and potential sources of arsenic and water-soluble ions in the snow at Ili River Valley, China.

Trace elements and water-soluble ions in snow can be used as indicators to reveal natural and anthropogenic emissions. To understand the chemical composition, characteristics of snow and their potential sources in the Ili River Valley (IRV), snow samples were collected from 17 sites in the IRV from December 2018 to March 2019. Inverse distance weighting, enrichment factor (EF) analysis, and backward trajectory modelling were applied to evaluate the spatial distributions and sources of water-soluble ions and dissolved arsenic (As) in snow. The results indicate that Ca2+ and SO42- were the dominant ions, and the concentrations of As ranged from 0.09 to 0.503 µg L-1. High concentrations of As were distributed in the northwest and middle of the IRV, and the concentrations of the major ions were high in the west of the IRV. The strong correlation of As with F-, SO42-, and NO2- demonstrates that As mainly originated from coal-burning and agricultural activities. Principal component analysis showed that the ions originated from a combination of anthropogenic and crustal sources. The EFs showed that K+, SO42-, and Mg2+ were mainly influenced by human activities. Backward trajectory cluster analysis suggested that the chemical composition of snow was affected by soil dust transport from the western air mass, the unique terrain, and local anthropogenic activities. These results provide important scientific insights for atmospheric environmental management and agricultural production within the IRV.

Stability evaluation of gardenia yellow pigment in presence of different phenolic compounds.

Gardenia yellow pigment (GYP) may undergo chemical degradation under different conditions resulting in color fading. This study investigated the effects of different phenolic compounds (caffeic acid, rosmarinic acid, tannic acid, epicatechin, chlorogenic acid, epigallocatechin, and epigallocatechin gallate) on the physical and chemical stability of GYP under light and different temperatures. Furthermore, food models with GYP/phenolic compounds were simulated to evaluate the GYP stability under different cooking methods. The addition of phenolic compounds, especially tannic acid, epigallocatechin gallate, epigallocatechin, and rosmarinic acid, significantly improved the GYP stability during light and thermal treatments. Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy confirmed that the formation of hydrogen bonds between GYP and selected phenolic compounds (tannic acid, epigallocatechin gallate, epigallocatechin, and rosmarinic acid), which may lead to the enhancement of GYP stability. Moreover, these selected phenolic compounds provided potent protective effects on GYP under different cooking methods.

Electrochemical aptasensor based on Mo2C/Mo2N and gold nanoparticles for determination of chlorpyrifos.

Two-dimensional Mo2C/Mo2N composites were synthesized by high temperature ball milling and used as support materials for fabricating a chlorpyrifos (CPF) aptasensor. Gold nanoparticles (Au NPs) were electrodeposited on the surface of a Mo2C/Mo2N-modified electrode to connect with the ferrocene (Fc) probe via Au-S bonds. The Fc probe can hybridize with the aptamer probe to form a double-stranded structure. The addition of CPF made the double strands melt and the Fc probe approached the surface of the electrode, thereby resulting in amplification of the electrochemical response. The current response of the aptasensor for detecting CPF in solutions linearly varied from 0 to 400 ng mL-1 (with a maximum at 0.98 V vs. Ag/AgCl). The Au NPs/Mo2C/Mo2N composites exhibited satisfactory electrochemical behavior due to their excellent electrical conductivity and large surface area. This ultrasensitive aptasensor showed a low limit of detection of 0.036 ng mL-1. It was applied to determine CPF in real samples with acceptable recoveries from 94.7 to 116.7%, and the relative standard deviation was from 2.57 to 7.08%.Graphical abstract Schematic diagram of the manufacturing process of the aptasensor. Electrochemical aptasensor based on Mo2C/Mo2N/Au NP composites show excellent performance in detecting CPF.

Degradation and mechanism analysis of chloroxylenol in aqueous solution by gas-liquid discharge plasma combined with ozonation.

Gas-liquid discharge non-thermal plasma (NTP) coupled with an ozonation reactor was used to investigate the removal of a broad-spectrum antibacterial agent, chloroxylenol (PCMX), from aqueous solution. Under the same experimental conditions (discharge power of 50.25 W, the initial concentration of PCMX of 60 mg L-1, oxygen flow of 1.0 L min-1 and PCMX solution flow of 150 mL min-1), the PCMX degradation rates in the ozonation-only, NTP-only and NTP/O3 systems were 29.25%, 67.04% and 79.43%, respectively. Correspondingly, the energy efficiency has also been greatly improved, and increased to 0.45, 1.03 and 1.21 g kW-1 h-1. In addition, the effects of the initial concentration of PCMX, initial pH, the flow rate of oxygen, the addition of H2O2 and the addition of a radical scavenger on the degradation rate of PCMX were investigated in the NTP/O3 system. The degradation rate in acidic solutions was higher than that in alkaline solutions. During the removal process of PCMX, the rate of degradation was strongly increased with the addition of H2O2 and acutely decreased with the addition of the radical scavenger. Compared with deionized water the degradation rates of PCMX in secondary effluent were inhibited. Four main intermediates of PCMX degradation by the NTP/O3 system were identified by gas chromatography-mass spectrometry (GC-MS) and a possible degradation pathway of PCMX was proposed. The changes in toxicity of the PCMX solution during the NTP/O3 system oxidation process were also evaluated using bioluminescent bacteria and Quantitative Structure Activity Relationship (QSAR) models with the help of the ECOSAR software.

Microfiber from textile dyeing and printing wastewater of a typical industrial park in China: Occurrence, removal and release.

Microfibers (MFs) are fibrous micro particles of longitude <5 mm, including natural fibers and fibrous microplastics. Microplastic pollution has become a world issue. As the major section of fiber production and processing, textile industry is an important potential source of microfibers, while receiving limited attention. To better understand the source and fate of textile microfibers, in this study, a typical textile industrial park in China is selected as the studying site. Microfibers in textile wastewater from typical textile mills and centralized wastewater treatments plants (WWTPs) of the park, and microfibers in nearby surface water were identified and characterized. The main results showed that the microfiber concentration in textile printing and dyeing wastewater could reach as high as 54,100 MFs/L. Although the removal efficiencies of microfibers by existing wastewater treatment processes can be over 85%, the average microfiber concentration in the effluents from the centralized WWTPs of the industrial park still reached 537.5 MFs/L, releasing 430 billion microfiber items per day. Microfiber release from textile wastewater is considerably higher than that from municipal sewage treatment plants, making it a significant contributor to microfibers in natural water bodies. Small-sized and colored microfibers increased in proportion in the treated effluents. Given the complex textile wastewater constituents, the potential negative environmental impacts of textile microfibers may be intensified by the enhanced adsorption and transfer of textile pollutants through these microfibers.

Relationships Among Character Strengths, Self-efficacy, Social Support, Depression, and Psychological Well-being of Hospital Nurses.

PURPOSE: From the perspective of positive psychology, our study aimed to explore depressive symptoms and psychological well-being among Chinese nurses, as well as analyze the impacts of character strengths, self-efficacy and social support on the mental health of nurses. METHODS: A cross-sectional and descriptive design using five self-reported questionnaires was used to investigate a cohort of 4238 nurses during 2018. A structural equation modeling analysis was used to verify a hypothetical model linking character strengths, self-efficacy, social support, depressive symptoms, and psychological well-being. RESULTS: The prevalence of depression among this cohort of Chinese nurses was 58.1%. The mean scores for caring, inquisitiveness, and self-control were 19.93 (SD = 2.82), 15.94 (SD = 3.00), and 16.34 (SD = 2.95), respectively. The hypothesized model was a good fit of the data (χ2/df = 1.77, p = .183, root mean square error of approximation = 0.04, goodness of fit index = 1.00, comparative fit index = 1.00, Tucker-Lewis index = 1.00). Except for the path from self-control to depression, the other hypothetical paths investigated were statistically significant. CONCLUSION: Character strengths were directly and positively associated with psychological well-being. Inquisitiveness was the strongest direct protective factor for depression. In addition, character strengths indirectly alleviated depression and increased psychological well-being through mediating variables of social support and self-efficacy. This study should alert nurse managers that more attention should be paid to the character strengths and mental health of nurses. This study provides evidence for interventions based on character strengths as a management strategy to support the mental health of nurses.

Astragaloside IV inhibits palmitate-mediated oxidative stress and fibrosis in human glomerular mesangial cells via downregulation of CD36 expression.

BACKGROUND: The increased influx of free fatty acids (FFAs) into the kidney is a risk factor for diabetes nephropathy (DN). In the present study we investigated the effects of astragaloside IV (AS-IV) on FFA-induced lipid accumulation, oxidative stress, and activation of TGF-ß1 signaling in human glomerular mesangial cells (HMCs). METHODS: A DN model was induced in Sprague Dawley rats by the administration of a high-fat diet and streptozocin, and HMCs were stimulated with palmitate. Lipid accumulation and FFA uptake were detected using Oil Red O and BODIPY™ FL C16 staining, respectively. The expression levels of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, p22phox, and CD36 were evaluated by western blotting or immunofluorescence/immunohistochemistry. The level of reactive oxygen species (ROS) was detected using 2',7'-dichlorofluorescein diacetate and dihydroethidium. RESULTS: Exposure to palmitate induced marked lipid accumulation in HMCs, whereas co-treatment with AS-IV significantly attenuated this phenomenon. Moreover, AS-IV suppressed palmitate-induced expression of TGF-ß1, p-Smad2/3, FN, Col4 A1, NOX4, and p22phox, in addition to ROS production. Notably, AS-IV reduced the palmitate-induced expression of CD36 in HMCs and DN rats. Treatment of HMCs with the CD36 inhibitor, sulfo-N-succinimidyl oleate (SSO), significantly attenuated FFA uptake, oxidative stress, and fibrosis. Nevertheless, the combined use of SSO and AS-IV did not enhance the efficacy. CONCLUSION: AS-IV inhibited palmitate-induced HMCs oxidative stress and fibrosis via the downregulation of CD36 expression, mediating FFA uptake and lipid accumulation.

Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats.

Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Renal tubular injury plays an important role in the development and progression of DN. And apoptosis of renal tubular epithelial cells (RTEC) contribute to the loss of renal function, increased levels of serum creatinine (SCr), blood urea nitrogen (BUN), urine total protein to urine creatinine and microalbuminuria and reduction of creatinine clear rate (CCr). Moreover, recent findings suggested that endoplasmic reticulum (ER) stress may lead to apoptosis of renal cells. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-apoptosis. Thus, in this study we investigated the effects and mechanisms of AS-IV on apoptosis of RTEC in high-fat diets (HFD) and low-dose streptozotocin (STZ)-induced type 2 DN rats. The results showed that AS-IV (40, 80 mg/kg) could alleviate RTEC apoptosis in DN rats. Furthermore, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney were also improved by AS-IV. And AS-IV could reduce the expression of apoptosis-related proteins cleaved caspase-3, Bax/Bcl-2 ratio. ER stress-related proteins GRP78, p-PERK, ATF4 and CHOP were also inhibited by AS-IV in kidney of DN rats. Taken together, our study suggests that the protective effects of AS-IV may be related to inhibit ER stress-induced apoptosis through down-regulating the expression of p-PERK, ATF4 and CHOP. And our study provides a new theoretical basis for the clinical treatment of patients with kidney diseases.

Astragalosides IV protected the renal tubular epithelial cells from free fatty acids-induced injury by reducing oxidative stress and apoptosis.

Renal tubular injury is associated with the development of diabetic nephropathy (DN) and the end-stage renal disease (ESRD). Free fatty acids (FFAs)-associated lipotoxicity contributes to injury of proximal renal tubular epithelial (HK-2) cells in diabetes. Palmitic acid (PA) which is the most abundant saturated fatty acid in FFAs is closely associated with the gradual decline of renal function. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-inflammation and anti-oxidation. In the current study, we investigated the effects of AS-IV on PA-induced apoptosis of HK-2 cells and the underlying mechanisms. The results showed that AS-IV (10, 20, 40 µmol/L) could alleviate PA-induced apoptosis of HK-2 cells. We found that AS-IV reduced the expression of Bax and cleaved-caspase3, but increased the expression of Bcl-2 and phosphorylated Nrf2 in HK-2 cells. Moreover, AS-IV reduced the level of reactive oxygen species (ROS) in the cells. Our study suggests that AS-IV could protect against PA-induced apoptosis in HK-2 cells by inhibiting ROS generation and apoptotic protein expression. This study may provide a new theoretical option for the patients with type 2 diabetes.

Electrochemical mineralization pathway of quinoline by boron-doped diamond anodes.

Boron-doped diamond anodes were selected for quinoline mineralization, and the resulting intermediates, phenylpropyl aldehyde, phenylpropionic acid, and nonanal were identified and followed during quinoline oxidation by gas chromatography-mass spectrometry and high-performance liquid chromatography. The evolutions of formic acid, acetic acid, oxalic acid, NO2(-), NO3(-), and NH4(+) were quantified. A new reaction pathway for quinoline mineralization by boron-doped diamond anodes has been proposed, where the pyridine ring in quinoline is cleaved by a hydroxyl radical giving phenylpropyl aldehyde and NH4(+). Phenylpropyl aldehyde is quickly oxidized into phenylpropionic acid, and the benzene ring is cleaved giving nonanal. This is further oxidized to formic acid, acetic acid, and oxalic acid. Finally, these organic intermediates are mineralized to CO2 and H2O. NH4(+) is also oxidized to NO2(-) and on to NO3(-). The results will help to gain basic reference for clearing intermediates and their toxicity.

In situ induced metal-enhanced fluorescence: a new strategy for biosensing the total acetylcholinesterase activity in sub-microliter human whole blood.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (i.e., total AChE) in human blood are biomarkers for theranostic monitoring of organophosphate neurotoxin-poisoned patients. We developed an ultra-sensitive method to detect the total AChE activity in sub-microliter human whole blood based on in situ induced metal-enhanced fluorescence (MEF). Both AChE and BChE can catalyze the hydrolysis of the acetylthiocholine (ATCh) substrate and produce positively-charged thiocholine (TCh). TCh can reverse the negatively-charged surface of core-shell Ag@SiO2 nanoparticles (NPs). The negatively-charged fluorescent dye (8-hydroxypyrene-1,3,6-trisulfonic acid, HPTS) is then confined to the surface of Ag@SiO2 NPs and generates an enhanced fluorescence signal in situ. Changes in the surface charge of Ag@SiO2 NPs are monitored by Zeta potential, and the MEF effect is confirmed by the measurements of fluorescence time decay. AChE activity has a dynamic range of 0 U/mL to 0.005 U/mL and a detection limit of 0.05 mU/mL. The total AChE activity in the sub-microliter human whole blood could be determined; the results were further validated. Therefore, combining the AChE catalytic reaction with MEF provides a simple, ultra-sensitive, and cost-effective "in situ MEF" approach to determine the total AChE activity in human whole blood sample down to sub-microliters without matrix interferences. The strategy also allows potential usage in other tissues and other fields.

Label-free fluorometric detection of S1 nuclease activity by using polycytosine oligonucleotide-templated silver nanoclusters.

S1 nuclease has an important function in DNA transcription, replication, recombination, and repair. A label-free fluorescent method for the detection of S1 nuclease activity has been developed using polycytosine oligonucleotide-templated silver nanoclusters (dC12-Ag NCs). In this assay, dC12 can function as both the template for the stabilization of Ag NCs and the substrate of the S1 nuclease. Fluorescent Ag NCs could be effectively formed using dC12 as the template without S1 nuclease. In the presence of S1 nuclease, dC12 is degraded to mono- or oligonucleotide fragments, thereby resulting in a reduction in fluorescence. S1 nuclease with an activity as low as 5×10(-8)Uµl(-1) (signal/noise=3) can be determined with a linear range of 5×10(-7) to 1×10(-3)Uµl(-1). The promising application of the proposed method in S1 nuclease inhibitor screening has been demonstrated using pyrophosphate as the model inhibitor. Furthermore, the S1 nuclease concentrations in RPMI 1640 cell medium were validated. The developed method for S1 nuclease is sensitive and facile because its operation does not require any complicated DNA labeling or laborious fluorescent dye synthesis.