[Determination of four phenolic endocrine-disrupting chemicals in water by dispersive solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry based on metal-organic skeleton porous carbon materials].

Phenolic endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with the endocrine system and disrupt normal cell functions upon entering a living organism, leading to reproductive and developmental toxicity. Therefore, the development of a rapid and efficient analytical method for detecting phenolic EDCs in environmental waters is crucial. Owing to the low concentration of phenolic EDCs in environmental water, appropriate sample pretreatment methods are necessary to remove interferences caused by the sample matrix and enrich the target analytes before instrumental analysis. Dispersive solid-phase extraction (DSPE) has gained considerable attention as a simple and rapid sample pretreatment method for environmental-sample analysis. In this method, an adsorbent material is uniformly dispersed in a sample solution and the target analytes are extracted through processes such as vortexing. Compared with traditional solid-phase extraction (SPE), DSPE increases the contact area between the adsorbent and sample solution, reduces the required amounts of adsorbent and organic solvents, and improves the extraction efficiency. The adsorbent material plays a critical role in DSPE because it determines the extraction efficiency of the method. Metal-organic frameworks (MOFs) are porous framework materials composed of metal clusters and multifunctional organic ligands. They possess many excellent properties such as tunable pore sizes, large surface areas, and good thermal and chemical stability, rendering them ideal adsorbent materials for sample pretreatment. MOF-derived porous carbon materials obtained through high-temperature carbonization not only increase the density of MOF materials for better separation but also retain the advantages of a large surface area, highly ordered porous structure, and high porosity. In this study, a porous carbon material derived from an MOF, named as University of Oslo-66-carbon (UiO-66-C), was synthesized using a solvothermal method and applied as an adsorbent to enrich four phenolic EDCs (bisphenol A, 4-tert-octylphenol, 4-nonylphenol, and nonylphenol) in water. A method combining DSPE with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to analyze these phenolic EDCs in water. The UiO-66-C dosage, pH of water sample, adsorption time, eluent type and volume, elution time, and ion strength were optimized. Gradient elution was performed using methanol-water as the mobile phase. The target analytes were separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and multiple reaction monitoring (MRM) was conducted in negative electrospray ionization mode. The method exhibited a linear correlation within the range of 0.5-100 µg/L for the four phenolic EDCs. The limits of detection (LODs) and quantification (LOQs) of the four phenolic EDCs were 0.01-0.13 µg/L and 0.03-0.42 µg/L, respectively. The precision of the method was evaluated through intra- and inter-day relative standard deviations (RSDs), with values ranging from 1.5% to 10.6% and from 6.1% to 13.2%, respectively. When applied to the detection of phenolic EDCs in tap and surface water, the spiked recoveries of the four phenolic EDCs were 77.1%-116.6%. Trace levels of 4-nonylphenol and nonylphenol were detected in surface water at levels of 1.38 and 0.26 µg/L, respectively. The proposed method exhibits good accuracy and precision; thus, it provides a new rapid, efficient, and sensitive approach for the detection of phenolic EDCs in environmental water.

Metal-Organic Framework-Based Composites for the Adsorption Removal of Per- and Polyfluoroalkyl Substances from Water.

The increasing health risks posed by per- and polyfluoroalkyl substances (PFASs) in the environment highlight the importance of implementing effective removal techniques. Conventional wastewater treatment processes are inadequate for removing persistent organic pollutants. Recent studies have increasingly demonstrated that metal-organic frameworks (MOFs) are capable of removing PFASs from water through adsorption techniques. However, there is still constructive discussion on the potential of MOFs in adsorbing and removing PFASs for large-scale engineering applications. This review systematically investigates the use of MOFs as adsorbents for the removal of PFAS in water treatment. This primarily involved a comprehensive analysis of existing literature to understand the adsorption mechanisms of MOFs and to identify factors that enhance their efficiency in removing PFASs. We also explore the critical aspects of regeneration and stability of MOFs, assessing their reusability and long-term performance, which are essential for large-scale water treatment applications. Finally, our study highlights the challenges of removing PFASs using MOFs. Especially, the efficient removal of short-chain PFASs with hydrophilicity is a major challenge, while medium- to long-chain PFASs are frequently susceptible to being captured from water by MOFs through multiple synergistic effects. The ion-exchange force may be the key to solving this difficulty, but its susceptibility to ion interference in water needs to be addressed in practical applications. We hope that this review can provide valuable insights into the effective removal and adsorption mechanisms of PFASs as well as advance the sustainable utilization of MOFs in the field of water treatment, thereby presenting a novel perspective.

Signaling pathways in brain ischemia: Mechanisms and therapeutic implications.

Ischemic stroke occurs when the arteries supplying blood to the brain are narrowed or blocked, inducing damage to brain tissue due to a lack of blood supply. One effective way to reduce brain damage and alleviate symptoms is to reopen blocked blood vessels in a timely manner and reduce neuronal damage. To achieve this, researchers have focused on identifying key cellular signaling pathways that can be targeted with drugs. These pathways include oxidative/nitrosative stress, excitatory amino acids and their receptors, inflammatory signaling molecules, metabolic pathways, ion channels, and other molecular events involved in stroke pathology. However, evidence suggests that solely focusing on protecting neurons may not yield satisfactory clinical results. Instead, researchers should consider the multifactorial and complex mechanisms underlying stroke pathology, including the interactions between different components of the neurovascular unit. Such an approach is more representative of the actual pathological process observed in clinical settings. This review summarizes recent research on the multiple molecular mechanisms and drug targets in ischemic stroke, as well as recent advances in novel therapeutic strategies. Finally, we discuss the challenges and future prospects of new strategies based on the biological characteristics of stroke.

Heart Sound Classification Network Based on Convolution and Transformer.

Electronic auscultation is vital for doctors to detect symptoms and signs of cardiovascular diseases (CVDs), significantly impacting human health. Although progress has been made in heart sound classification, most existing methods require precise segmentation and feature extraction of heart sound signals before classification. To address this, we introduce an innovative approach for heart sound classification. Our method, named Convolution and Transformer Encoder Neural Network (CTENN), simplifies preprocessing, automatically extracting features using a combination of a one-dimensional convolution (1D-Conv) module and a Transformer encoder. Experimental results showcase the superiority of our proposed method in both binary and multi-class tasks, achieving remarkable accuracies of 96.4%, 99.7%, and 95.7% across three distinct datasets compared with that of similar approaches. This advancement holds promise for enhancing CVD diagnosis and treatment.

Review of the Protective Mechanism of Paeonol on Cardiovascular Disease.

Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.

The Establishment of a Tobramycin-Responsive Whole-Cell Micro-Biosensor Based on an Artificial Ribozyme Switch.

In this study, a tobramycin concentration-dependent whole-cell micro-biosensor (tob-HHAz) was constructed by fusing a tobramycin aptamer with a hammerhead ribozyme (HHR) from Schistosoma mansoni. The biosensor was obtained by integrating all the modules into one complete RNA sequence, which was easily introduced into E. coli without suffering from harsh external environments. Three independent tobramycin-sensitive RNA structures were identified via high-throughput screening in vivo and were further verified in vitro to undergo the desired self-cleavage reaction. The computation prediction of the RNA structure was performed to help analyze the mechanisms of various conformations by performing a qualitative and rapid detection of tobramycin in practical samples; two sensors exhibited high responsiveness to spiked milk, with a detection limit of around 40 nM, which is below the EU's antibiotic maximum residual level. One of the structures provides a linear range from 30 to 650 nM with a minimum detection limit of 30 nM and showed relatively good selectivity in spiked urine. This study is the first in which in vivo screening was combined with computation analysis to optimize the pivotal structure of sensors. This strategy enables researchers to use artificial ribozyme-based biosensors not only for antibiotic detection but also as a generally applicable method for the further detection of substances in living cells.

The covalent organic framework based nylon membrane extraction coupled with UHPLC-MS/MS for highly efficiency determination of hexabromocyclododecanes in environmental water.

Hexabromocyclododecanes (HBCDs) have given their adverse effects on environment and human health, and highly sensitive analysis of HBCDs in water is urgent. In this study, a new method for the determination of trace HBCDs in water was established by covalent organic framework (COF) based nylon membrane extraction (ME) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The COF had been self-assembled onto the nylon membrane in a gentle strategy to fabricate COF nylon membrane. Several important ME parameters including the dosage of COF, pH, eluent condition and salinity were systematically investigated. The limits of detection and quantification were 0.011-0.014 and 0.038-0.047 ng/L for three HBCDs, respectively. The linear ranges were from 0.04 to 20 ng/L, and the relative standard deviations were 5.7-17.8 % (intra-day) and 5.2-14.1 % (inter-day). In addition, density functional theory (DFT) calculations on adsorption energy proved that the introduction of halogen bond (XB) made a key contribution to high extraction efficiency and excellent selectivity of COF nylon membrane for HBCDs. The 500 mL of samples, including tap water and reservoir water, could be extracted only in 23 min. The established method presented highly sensitive for ultra-trace analysis of HBCDs in environmental water.

[Determination of four fungicides in water by magnetic solid phase extraction-ultrahigh performance liquid chromatography-tandem mass spectrometry using covalent organic framework material].

Fungicides can lead to soil and plant diseases after long-term enrichment in the environment; they can also penetrate deeper into the soil and groundwater by rainwater or irrigation, threatening the water environment and human health. Therefore, it is crucial to develop a simple, rapid, efficient, and sensitive analytical method for the detection of fungicides in the water environment. Sample pretreatment is important for the extraction and enrichment of pollutants from environmental water. Magnetic solid phase extraction (MSPE) is a new sample pretreatment method, which uses magnetic materials as adsorbents dispersed in solution, and rapid separation can be achieved by the aid of external magnets. Because of its advantages of short analytical time, less organic solvent consumption, and easy separation of adsorbents, MSPE has attracted much attention. The key to MSPE is the preparation of highly selective magnetic adsorbents. Covalent organic frameworks have the advantages of large surface area, good chemical and thermal stability, tunable porous structure, low density, and easy functionalization, all of which are ideal for adsorbing fungicides. The concentration of fungicides in environmental water is low. Ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has high sensitivity and high selectivity, which is suitable for the analysis of fungicides. In this work, a magnetic covalent organic framework Fe3O4@TpBD was prepared by an in situ method, as the MSPE sorbent material to enrich of benzimidazole fungicides (thiabendazole, carbendazim, fuberidazole) and organic sulfur fungicide (isoprothiolane) in environmental water. An extraction method based on π-π conjugation, hydrogen bonding, and electrostatic interaction between Fe3O4@TpBD and the fungicides, in combination with UHPLC-MS/MS, was developed for the determination of four trace fungicides in water. Transmission electron microscopy (TEM), X-ray diffractometry (XRD), and Fourier transform-infrared spectroscopy (FT-IR) were performed to confirm the successful synthesis of Fe3O4@TpBD and to characterize this material. A series of experiments were carried out to decide the optimal extraction conditions, i. e., the magnetic ratio and dosage of Fe3O4@TpBD, pH of the water sample, adsorption time, type and volume of the eluent, elution time, and salinity. Gradient elution was carried out with methanol-water as the mobile phase. The target analytes were separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization mode. The ion source temperature and ion source voltage were set to 500 ℃ and 5 kV, respectively. The analytical method was established under the optimized extraction conditions. The four fungicides showed good linearity in the range of 3-1200 ng/L, with linear correlation coefficients greater than 0.998. The limits of detection (LODs) and limits of quantification (LOQs) of this developed method were 0.06-0.28 ng/L and 0.20-0.92 ng/L, respectively. Recovery tests were performed at three spiked levels of 15, 150, and 600 ng/L, with relative standard deviations of 2.8% to 10.0% (intra-day) and 4.4% to 15.7% (inter-day). The accuracy of the established analytical method was investigated by using it to test real water samples, and satisfactory recoveries for the four analytes were achieved within 77.1% to 119.1%. Trace amounts of carbendazim were detected in the reservoir water at 27.5 ng/L. The method has good sensitivity, accuracy, and precision, and the operation process is convenient.

Fu Fang Zhen Zhu Tiao Zhi Capsules Protect against Myocardial Ischemia by Inhibiting Cardiomyocyte Pyroptosis.

Background: Fu Fang Zhen Zhu Tiao Zhi (FTZ) is a traditional Chinese herbal prescription widely used to treat dyslipidemia, metabolic diseases, and diabetic coronary disorders. Cardiomyocyte death and loss of regenerative ability cause cardiac dysfunction and heart failure. FTZ can effectively treat diabetic cardiomyopathy and macrovascular diseases; however, the mechanism behind the phenomenon is still unclear. Here, we determined the mechanism of action of FTZ in treating myocardial infarction. Methods: Male C57BL/6 mice were treated with 2.4 or 1.2 g/kg FTZ, or administered saline by oral gavage daily for four weeks, and a 24-hour ligation was administered to the artery. Echocardiography was used to evaluate cardiac function. Hematoxylin and eosin and Evans blue/triphenyltetrazolium chloride staining were carried out by staining the cardiac tissue, used to evaluate cardiac function and infarct size. Using western blotting and reverse transcriptase-polymerase chain reaction, we determined the relative levels of NOD-like receptor protein (NLRP) 3, ASC, cleaved caspase-l (C-Caspase-1), GSDMD, and GSDMD-N. TUNEL, immunohistochemical, and immunofluorescence staining were used to determine cell death and NLRP3 expression. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-1ß and IL-18. Results: FTZ reduced ischemia-induced cardiomyocyte cell death in vivo and H2O2-induced cell death in vitro by maintaining cardiac architecture and restoring cardiac function. FTZ decreased the NLRP3 expression and inhibited pyroptosis-correlated genes, including NLRP3, ASC, GSDMD, C-Caspase-1, and GSDMD-N. NLRP3 overexpression impaired the efficacy of FTZ by inducing pyroptosis. Conclusion: FTZ could preserve cardiac function resulting from ischemic insult by inhibiting pyroptosis, which was partially reversed by NLRP3 overexpression, indicating that NLRP3 could be a potential target of FTZ in treating myocardial infarction.

[Progress in sample pretreatment and detection methods of hexabromocyclododecanes].

Hexabromocyclododecanes (HBCDs) are a group of brominated flame retardants that are extensively employed in the industrial production of plastics, furniture, and construction materials. Due to their regular use and massive emissions, HBCDs have been distributed in the environment (air, water, soil, and sediments). Due to their high toxicity, persistent and long-distance transport, and bioaccumulation, HBCDs were listed in the Stockholm Convention in 2013. Thus, the accurate analysis and strict control of the pollution levels of HBCDs in environmental samples are critical to the government's long-term environmental supervision mechanism. However, the concentration levels of HBCDs in real samples are low, combined with complex matrices, which seriously limits the determination of HBCDs. The target isomers are particularly transformed or degraded, which makes analysis challenging due to the high temperatures and specific organic solvents. The physicochemical features, toxic and environmental dangers, usage, and standard limitations of HBCDs are briefly discussed herein. Sample pretreatment and instrument detection of HBCDs in various matrices are summarized (i. e., soil, sediment, food, electronics, atmosphere, animals, and water). More than 70 research papers (2000-2022) from the Science Citation Index (SCI) and Chinese core publications are cited herein. First, the entire process of extraction, purification, separation, and enrichment of HBCDs is compared, including soxhlet extraction (SE), ultrasonic-assisted extraction (UAE), accelerated solvent extraction(ASE), supercritical fluid extraction (SFE), solid phase extraction (SPE), dispersed solid phase extraction (DSPE), liquid-liquid extraction (LLE), dispersive liquid-liquid microextraction (DLLME), and solid phase microextraction (SPME). In the literature, UAE is the most commonly employed process, accounting for a quarter of all HBCDs sample pretreatments. Additionally, SPE sample pretreatment technology can completely separate the targets and impurities to reduce the effect of matrix; and enrich the targets to improve sensitivity of method. By using SPE technology, the enrichment factor can be increased due to the massive sample volume, thus enabling detect HBCDs concentrations (nanogram per liter level) in water. Second, the advantages and disadvantages of instrument approaches are examined and discussed, including gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS), which offer a reference for meeting the requirements in the determination of HBCDs in real samples, i. e., the total HBCDs can be detected by GC or GC-MS and three HBCD isomers (α-HBCD, ß-HBCD, γ-HBCD) can be determined by LC or LC-MS. By using the triple quadrupole mass spectrometer, the sensitivity of the method can be improved. Till date, LC-MS/MS has been chosen as an instrument for the determination of HBCDs in various matrices (i. e., seawater, marine sediment, marine organisms, toys, and electronic products) in China. However, there are several challenges. The sample pretreatment is tedious; large sample volumes and organic solvent utilization. These challenges point to the development trends of analytical approaches for HBCDs. The development of green, automated, low-cost, fast, and efficient sample pretreatment approaches for new adsorption materials is the main development direction in the analysis of HBCDs in the future.

Treadmill training improves respiratory function in rats after spinal cord injury by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway.

OBJECTIVE: To investigate the effects of treadmill training on lung injury and HMGB1/TLR4/NF-κB after spinal cord injury (SCI) in rats. METHODS: A total of 108 female SD rats were randomly divided into three groups: sham operation group, SCI brake group, and SCI exercise group. The rats in the SCI exercise group began treadmill training on the 3rd day after the operation. The rats in the SCI brake group underwent braking treatment. The lung tissues were obtained on the 3rd, 7th, and 14th days after exercise. Locomotor functional recovery was determined using the BBB scores and inclined plane test. Respiratory function was determined via abdominal aortic blood gas analysis. HE staining was used to detect pathological changes in rat lung tissue. RNA sequencing was used to identify differentially expressed genes at different phases in each group of lung tissues. HMGB1, TLR4, and NF-κB in lung tissue were detected using immunohistochemistry and immunofluorescence. Detection of HMGB1 levels in serum, spinal cord tissues and lung tissues by ELISA. HMGB1, TLR4, NF-κB, IL-1ß, IL-6, TNF-α mRNA, and protein expression levels were detected via qRT PCR and western blot. RESULTS: Motor and respiratory functions significantly decreased after SCI (P < 0.05). However, locomotion and respiratory functions were significantly improved after treadmill training intervention (P < 0.05). HE staining showed that interstitial thickening, inflammatory cells, and erythrocyte infiltration occurred in lung tissue of rats after SCI (P < 0.05). Moreover, inflammatory reaction in lung tissue was significantly reduced after treadmill training intervention (P < 0.05). A total of 428 differentially expressed mRNAs [(|log2(FC)| > 2, P < 0.05)] were identified in the intersection of the three groups. KEGG analysis identified five enriched signal pathways, including NF-kappa B. ELISA results showed that treadmill training could significantly reduce the levels of HMGB1 in serum, spinal cord tissue and lung tissue that were elevated after SCI (P < 0.05). Immunohistochemistry, immunofluorescence, qRT PCR, and Western blot showed that HMGB1, TLR4, IL-1ß, IL-6, TNF-α, and NF-κB expressions were significantly up-regulated at the 3rd, 7th and 14th days after SCI, compared with the sham group. Besides, inflammatory cytokines were significantly lower in the SCI exercise group than in the SCI brake group at all time points after intervention (P < 0.05). CONCLUSION: Treadmill training alleviates lung tissue inflammation and promotes recovery of motor and respiratory functions by inhibiting the HMGB1/TLR4/NF-κB signaling pathway after SCI in rats.

Simultaneous preconcentration and pre-column derivatization for rapid analysis of nitrilotriacetic acid in environmental waters by high performance liquid chromatography.

A simplified sample pretreatment procedure was developed for quantitative measurement of nitrilotriacetic acid (NTA) in environmental water. On the basis of coordination capacity between NTA and metal ions, aluminum-based metal organic framework (MOF, MIL-53(Al)) was adopted for the adsorption of NTA, followed by stripping with copper sulfate as the eluent. The adsorbed NTA was converted into Cu-NTA during the desorption process, which facilitated the ensuing measurement by high performance liquid chromatography (HPLC). A linear range within 0.10 - 10 mg L-1 was achieved, along with a limit of detection (LOD, S/N=3, n=7) of 0.03 mg L-1 and an enrichment factor of 10.4. The developed method was validated by the analysis of sea water, influent of wastewater treatment plant and industrial wastewater, with satisfactory recoveries (90.2 - 91.1%) obtained.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against atherosclerosis by suppressing EndMT via modulating Akt1/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi (FTZ) is a traditional Chinese herbal prescription that has been used to treat dyslipidemia, nonalcoholic fatty liver disease, atherosclerosis, diabetes and its complications in the clinic for almost ten years. Endothelial-mesenchymal transition (EndMT) is the key driver of atherosclerosis. However, the effects of FTZ on endothelial dysfunction and EndMT remain unknown. AIM OF THE STUDY: To evaluate the therapeutic effects of FTZ against EndMT and the underlying mechanisms. MATERIALS AND METHODS: An in vivo model of atherosclerosis was established by feeding ApoE-/- mice with a high-fat diet (HFD). The body weight, lipid levels, plaque area, lipid deposition and EndMT were evaluated using standard assays 12 weeks after intragastric administration of FTZ and simvastatin. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to simulate EndMT in vitro. The degree of EndMT was assessed after treating the cells with FTZ or transfection with si-Akt1. The expression levels of genes involved in EndMT were quantified by real-time PCR or western blotting. RESULTS: FTZ ameliorated dyslipidemia and endothelial dysfunction in the atherosclerotic mice. In addition, FTZ reduced body weight and the total cholesterol, triglycerides and low-density lipoprotein levels, and increased that of high-density lipoproteins. FTZ also upregulated the expression of endothelial markers (CD31 and VE-cadherin) and decreased that of mesenchymal markers (ɑ-SMA and FSP1), indicating that it inhibits EndMT. Knocking down Akt1 exacerbated EndMT and reversed the therapeutic effect of FTZ. CONCLUSION: FTZ delayed atherosclerosis by inhibiting EndMT via the Akt1/ß-catenin pathway.

Metabolic dysfunction-associated fatty liver disease and liver fibrosis: Prevalence and associated factors in the middle-aged and older US population.

AIM: The global burden of chronic liver disease is substantial. Limited studies have reported the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis among middle-aged and older people. Therefore, we aimed to determine the nationwide prevalence of and associated factors for MAFLD and fibrosis in adults aged 45-79 years from the United States. METHODS: This cross-sectional study utilized data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey conducted with a nationally representative sample of the civilian, noninstitutionalized US population. Hepatic steatosis and fibrosis were assessed by transient elastography with controlled attenuation parameter and liver stiffness measurement, respectively. RESULTS: A total of 1186 eligible participants aged 45-79 years were finally included in the analyses. The estimated prevalence of MAFLD, significant fibrosis (F ≥ F2), and advanced fibrosis (F ≥ F3) was 48.6% (95% confidence interval [CI], 43.1%-54.0%), 9.5% (95% CI, 6.8%-12.7%), and 6.7% (95% CI, 4.1%-10.1%), respectively. Multivariable logistic regression revealed an increased MAFLD predisposition in subjects with metabolic disorders including overweight/obesity, abdominal obesity, hypertension, and diabetes mellitus. Moreover, the presence of depression was an independent and strong predictor of MAFLD risk (odds ratio = 3.23; 95% CI, 1.37-7.11). Elevated liver enzymes, hypertension, diabetes mellitus, hepatitis virus infection, and steatosis were associated with a high risk of significant fibrosis. CONCLUSIONS: Newly defined MAFLD is highly prevalent in the US middle-aged and older population. Approximately 1 in 10 people has significant liver fibrosis. In addition to metabolic disorders, the presence of depression potentially increases the risk of MAFLD.

Determination of nitric oxide using light-emitting diode-based colorimeter with tubular porous polypropylene membrane cuvette.

On the basis of the Griess-Saltzman (GS) reaction, an optical device for nitric oxide (NO) detection in exhaled breath and atmosphere was developed by employing the light-emitting diode (LED, 560 nm) as the light source, light-to-voltage converter (LVC) as the detector, and porous polypropylene membrane tube (PPMT) as the cuvette. The PPMT was filled with GS reagents and covered with a coaxial jacket tube for gas collection and color reaction; two ends of the PPMT were connected with the LED and LVC to detect the change of light transmissivity in the wavelength range of 530 to 590 nm mainly. A gas absorber filled with GS reagents was installed prior to another absorber filled with KMnO4 solution to eliminate the interference of coexisting NO2. Under the optimized experimental conditions, the device achieved a limit of detection (3σ/k) of 4.4 ppbv for NO detection. The linearity range of this device was divided into two segments, i.e., 25 to 100 ppbv and 50 to 1000 ppbv, with both coefficients of determination > 0.99. The relative standard deviation was 2.7% (n = 9, c = 100 ppbv), and the analytical time was 5.5 min per detection. The minimum detectable quantity was decreased to 1.18 ng, which was ~ 100 times lower than the original GS method (115 ng). The present device was applied for determination of NO in exhaled breath, vehicle exhaust, and air. In addition to satisfactory spiking recoveries (i.e., 103% and 107%), the analytical results of the present device were in agreement with the results obtained by the standard method. These results assured the practicality of the developed device for NO detection in real environmental samples.

Covalent organic framework-graphene oxide composite: A superior adsorption material for solid phase microextraction of bisphenol A.

Novel materials with high adsorption and desorption efficiencies are significant for studying compounds at ultra-trace level. Herein, covalent organic framework-graphene oxide (COF-GO) composite materials are synthesized, and tested for solid phase microextraction (SPME) of bisphenol A (BPA) at ultra-trace level. With GO modified successively by 3-aminopropyltriethoxysilane, 1,3,5-triformylphloroglucinol (Tp), and different ratios of COF monomers (Tp and benzidine (BD)), the composites of TpBD-GO-n (n = 1-4) are synthesized. By coating the composites on a glass fiber, the extraction performances of the composites for BPA are tested with constant flow desorption ionization mass spectrometry (CFDI-MS). The extraction efficiency of the composite TpBD-GO-2 is 2.2 and 4.7 times higher than those of TpBD and GO, respectively. The chromatographic separation becomes a non-essential step for detection of BPA, the analysis time for each sample is reduced to 8 min. The limits of detection and quantification of MS for BPA analysis are improved to be 22.2 and 73.9 ng L-1. The linear range is extended to be 10.0 µg L-1 (R2 = 0.9990), and the relative standard deviations of one fiber (n = 11) and fiber-to-fiber (n = 8) are 4.3% and 5.6% (1 µg L-1), respectively. With this method, ultra-trace levels of BPA present in river water and sea water samples can be successfully detected and quantified. The results indicate that the TpBD-GO-n composites possess superior extraction performance, and their various applications could be expected.

Oryza sativa RNA-Dependent RNA Polymerase 6 Contributes to Double-Strand Break Formation in Meiosis.

RNA-dependent RNA polymerase 6 (RDR6) is a core component of the small RNA biogenesis pathway, but its function in meiosis is unclear. Here, we report a new allele of OsRDR6 (Osrdr6-meiosis [Osrdr6-mei]), which causes meiosis-specific phenotypes in rice (Oryza sativa). In Osrdr6-mei, meiotic double-strand break (DSB) formation is partially blocked. We created a biallelic mutant with more severe phenotypes, Osrdr6-bi, by crossing Osrdr6-mei with a knockout mutant, Osrdr6-edit In Osrdr6-bi meiocytes, 24 univalents were observed, and no histone H2AX phosphorylation foci were detected. Compared with the wild type, the number of 21-nucleotide small RNAs in Osrdr6-mei was dramatically lower, while the number of 24-nucleotide small RNAs was significantly higher. Thousands of differentially methylated regions (DMRs) were discovered in Osrdr6-mei, implying that OsRDR6 plays an important role in DNA methylation. There were 457 genes downregulated in Osrdr6-mei, including three genes, CENTRAL REGION COMPONENT1, P31 comet , and O. sativa SOLO DANCERS, related to DSB formation. Interestingly, the downregulated genes were associated with a high level of 24-nucleotide small RNAs but less strongly associated with DMRs. Therefore, we speculate that the alteration in expression of small RNAs in Osrdr6 mutants leads to the defects in DSB formation during meiosis, which might not be directly dependent on RNA-directed DNA methylation.

CYCLIC NUCLEOTIDE-GATED ION CHANNELs 14 and 16 Promote Tolerance to Heat and Chilling in Rice.

Calcium signaling has been postulated to be critical for both heat and chilling tolerance in plants, but its molecular mechanisms are not fully understood. Here, we investigated the function of two closely related cyclic nucleotide-gated ion channel (CNGC) proteins, OsCNGC14 and OsCNGC16, in temperature-stress tolerance in rice (Oryza sativa) by examining their loss-of-function mutants generated by genome editing. Under both heat and chilling stress, both the cngc14 and cngc16 mutants displayed reduced survival rates, higher accumulation levels of hydrogen peroxide, and increased cell death. In the cngc16 mutant, the extent to which some genes were induced and repressed in response to heat stress was altered and some Heat Shock factor (HSF) and Heat Shock Protein (HSP) genes were slightly more induced compared to the wild type. Furthermore, the loss of either OsCNGC14 or OsCNGC16 reduced or abolished cytosolic calcium signals induced by either heat or chilling stress. Therefore, OsCNGC14 and OsCNGC16 are required for heat and chilling tolerance and are modulators of calcium signals in response to temperature stress. In addition, loss of their homologs AtCNGC2 and AtCNGC4 in Arabidopsis (Arabidopsis thaliana) also led to compromised tolerance of low temperature. Thus, this study indicates a critical role of CNGC genes in both chilling and heat tolerance in plants, suggesting a potential overlap in calcium signaling in response to high- and low-temperature stress.

Transforming growth factor-ß inhibits IQ motif containing guanosine triphosphatase activating protein 1 expression in lung fibroblasts via the nuclear factor-κB signaling pathway.

IQ motif containing guanosine triphosphatase activating protein 1 (IQGAP1) is associated with idiopathic pulmonary fibrogenesis (IPF); however, characterization of the expression of IQGAP1 in lung fibroblasts has remained elusive. The present study therefore evaluated IQGAP1 expression in mouse and human lung fibroblasts under fibrotic conditions via western blot analysis. It was revealed that IQGAP1 expression levels were significantly decreased in lung fibroblasts isolated from bleomycin-challenged mice than in those of control mice. Transforming growth factor-ß (TGF-ß) induced differentiation, as well as decreased expression of IQGAP1 in WI-38 cells human lung fibroblasts. Furthermore, inhibition of nuclear factor (NF)-κB activation restored the TGF-ß-induced inhibition of IQGAP1 expression in WI-38 cells. In lysophosphatidic acid (LPA)-challenged WI-38 cells, the expression of IQGAP1 was also decreased, while neutralized anti-TGF-ß antibody treatment restored the LPA-induced inhibition of IQGAP1 expression. These data indicated that TGF-ß inhibited IQGAP1 expression in lung fibroblasts via the NF-κB signaling pathway, presenting a potential novel therapeutic target for the treatment of IPF.

Transforming growth factor-Beta inhibits heme oxygenase-1 expression in lung fibroblast through nuclear factor-kappa-B-dependent pathway.

BACKGROUND: Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic conditions has not been studied. METHODS: This study was conducted to investigate the expression of HO-1 in lung fibroblasts from mice and humans under fibrotic conditions by Western blot. RESULTS: We found that the expression of HO-1 was significantly decreased in lung fibroblasts isolated from bleomycin-challenged mice in comparison with control mice. Transforming growth factor-ß (TGF-ß) inhibited HO-1 expression and induced differentiation in human lung fibroblasts. Pretreatment with nuclear factor-κB (NF-κB) activation inhibitor or knockdown of the NF-κB p65 subunit attenuated TGF-ß-induced inhibition of HO-1 expression and differentiation in human lung fibroblasts. Similarly, lysophosphatidic acid (LPA) induced TGF-ß expression and decreased HO-1 expression in human lung fibroblasts. Interestingly, pretreatment with neutralized anti-TGF-ß antibody attenuated LPA effects in human lung fibroblasts. CONCLUSION: These data suggested that TGF-ß inhibited HO-1 expression in human lung fibroblasts through activation of NF-κB.