New solution for predicting the removal efficiency of organic contaminants by UV/ H2O2: From a case study of 1H-benzotriazole.

Rapid prediction of the removal efficiency and energy consumption of organic contaminants under various operating conditions is crucial for advanced oxidation processes (AOPs) in industrial application. In this study, 1H-Benzotriazole (BTZ, CAS: 95-14-7) is selected as a model micropollutant, a validated incorporated Computational Fluid Dynamics (CFD) model is employed to comprehensively investigate the impacts of initial concentrations of H2O2, BTZ and dissolved organic carbon (DOC) (i.e., [DOC]0, [BTZ]0 and [DOC]0), as well as the effective UV lamp power P and volumetric flow rate Qv. Generally, the operation performance depends on [DOC]0 and [BTZ]0 in similar trends, but with quantitatively different ways. The increase in [H2O2]0 and P/Qv can promote •OH generation, leading to the elimination of BTZ. It is worth noting that P/Qv is found to be linearly correlated with the removal order of BTZ (ROBTZ) under specific conditions. Based on this finding, the degradation of other potential organic contaminants with a wide range of rate constants by UV/H2O2 is further investigated. A model for predicting energy consumption for target removal rates of organic pollutants is established from massive simulation data for the first time. Additionally, a handy Matlab app is first developed for convenient application in water treatment. This work proposes a new operable solution for fast predicting operation performance and energy consumption for the removal of organic contaminants in industrial applications of advanced oxidation processes.

[Ozone Pollution Characteristics and Formation Mechanism in a Typical Tropical Seaside City].

To investigate the pollution characteristics and formation mechanism of ambient air ozone(O3) in a typical tropical seaside city, we conducted an observational experiment on O3 and its precursors at an urban site in Haikou, Hainan Province, from June to October 2019. The O3 pollution characteristics were analyzed comprehensively; the O3-NOx-VOCs sensitivities and key precursors were determined, and the control strategies for O3 pollution were carried out. The results were as follows:1 O3 pollution in Haikou mainly occurred in September and October, with daily maximum 8-h O3 concentrations in the range of 39-190 µg·m-3, and the daily variation in O3 was unimodal, peaking at approximately 14:00. 2 The concentrations of NO2 and VOCs were higher during O3 pollution episodes than their respective mean values in Haikou City. The increased O3 precursor concentrations were an important factor leading to O3 pollution, whereas O3 pollution was also influenced by regional transport, with pollutants mainly transported from the northeastern part of Haikou City. 3 O3-NOx-VOCs sensitivity in Haikou City was in the VOCs and NOx transitional regime, and the most sensitive precursors in various months were different. O3 formation in September was sensitive to anthropogenic VOCs the most; however, in October it was sensitive to NOx. 4 In the future, the reduction ratio of VOCs to NOx should be 1:1-4:1 to control O3 pollution effectively in Haikou.

Systematic characterization of the metabolites of defatted walnut powder extract in vivo and screening of the mechanisms against NAFLD by UPLC-Q-Exactive Orbitrap MS combined with network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored. AIM OF THE STUDY: The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway. MATERIALS AND METHODS: To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies. RESULTS: A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism. CONCLUSION: Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.

Role of epigenetic modifications in the development of crops essential traits.

Epigenetic modification refers to the chemical modifications of chromosomal DNA and histones, mainly including DNA methylation, histone modifications and non-coding RNAs. Without altering the DNA sequence, these heritable modifications can affect gene expression profiles by changing the chromatin state and play an important role in regulating the growth and development of plants. When the specific epigenetic modifications are changed, crops can obtain excellent phenotypes and stronger environmental adaptability. Therefore, artificially changing the epigenetic modifications are expected to obtain high-quality germplasm resources more suitable for agricultural production. In this review, we summarize the main types of plant epigenetic modifications, highlight the research progresses of functional plant epigenetic modifications on the important traits and responses to environmental stress, and identify the main problems that need be solved in the application of epigenetics in crop improvement, thereby providing new insights for the functional epigenetic modifications on crop breeding and improvement.

Anti-NAFLD effect of defatted walnut powder extract in high fat diet-induced C57BL/6 mice by modulating the gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel has the actions of removing meteorism, dissipating stagnation and removing blood stasis and is used after being defatted in TCM. Defatted walnut powder extract (DWPE) has the abilities of anti-oxidation and lowering lipid levels in vivo. However, the effects and the potential mechanisms of DWPE on NAFLD have not been explored. AIM OF THE STUDY: The study were to investigate the anti-NAFLD effect of DWPE in high fat diet-induced C57BL/6 mice and demonstrate that whether DWPE developed the effect on anti-NAFLD by remodeling the compositions and abundances of gut microbiota. MATERIALS AND METHODS: The inhibitory effect of DWPE on the development of NAFLD was conducted on C57BL/6 mice with a high fat diet and the regulation effect of DWPE on gut microbiota was verified on pseudo-sterile mice with treatment of broad spectrum antibiotics. RESULTS: The results showed that the oral administration of DWPE remarkably alleviated hepatic lipid accumulation by decreasing the levels of TG, TC, LDL, MDA and increasing HDL. Meanwhile, the expressions of NF-κB and MAPKs family proteins were reduced by DWPE compared with HFD group. Otherwise, the efficacy of anti-NAFLD of DWPE was significantly decreased after treatment of antibiotics, which indicated the key role of gut microbiota in the therapeutic process. Furthermore, sequencing of 16S rRNA gene revealed that DWPE could revert the decreased relative abundance of gut microbiota caused by the long term of a high fat diet. And the disordered microflora was remodeled by DWPE including the reduction of Erysipelotrichia, Firmicutes and Actinobacteria as well as the increment of Bacteroidetes, Clostridiales, Bacteroidales S24-7, Prevotellaceae and Bacteroides. CONCLUSION: Taken together, DWPE had a preventing effect on NAFLD, which might be associated with the regulation of gut microbiota.

[Effect of Bushen Gujin Recipe on serum and synovia interleukin-1 and tumor necrosis factor-alpha of knee osteoarthritis model rabbits].

OBJECTIVE: To explore the effect of Bushen Gujin Recipe (BGR) on serum and synovial expression of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in knee osteoarthritis (KOA) model rabbits. METHODS: Totally 36 8-month-old healthy male New Zealand white rabbits were randomly divided into 4 groups, i.e., the normal control group, the model group, the Western medicine group (Meloxicam, at the daily dose of 6 mg/kg), and the TCM group (BGR, at the daily dose of 53 g/kg), 9 in each group. Modeling was performed in all rabbits except those in the normal control group by using Hulth A method. All medication was performed for 8 consecutive weeks. Contents of IL-1 and TNF-α were detected using ELISA from serum, partial synovial tissue of the front knee joint, cartilage and subchondral bone of the medial femoral condyle. RESULTS: The joint space became narrowed in the Western medicine group, ranging between the model group and the TCM group. The articular surface was rough with obvious osteophytes. The joint space was slightly narrower in the TCM group; the articular surface was slightly rough with mild osteophytes. Compared with the normal control group, contents of IL-1 and TNF-α in serum and synovial increased in the model group (P < 0.01). Compared with the model group, contents of IL-1 and TNF-α in serum and the synovial fluid decreased in the two treatment groups (P < 0.01). There was no statistical difference in contents of IL-1 and TNF-α between the Western medicine group and the TCM group. CONCLUSION: BGR promoted the synthesis of cartilage matrix and carti- lage repair through inhibiting the secretion of IL-1 and TNF-α, and prolonging cartilage degeneration.

The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.

Neuroprotective effects of ultra-low-molecular-weight heparin on cerebral ischemia/reperfusion injury in rats: involvement of apoptosis, inflammatory reaction and energy metabolism.

Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction.

Antagonistic effects of ultra-low-molecular-weight heparin on Aß25-35-induced apoptosis in cultured rat cortical neurons.

Low-molecular-weight heparin (LMWH) and ultra-low-molecular-weight heparin (ULMWH) are heparin's derivatives, having various pharmacological effects. The present study aims to investigate the effect of ULMWH on amyloid ß peptide (Aß25-35)-induced neurotoxicity in cultured rat cortical neurons, and LMWH was employed as a positive control agent. The neurons were incubated with Aß25-35 (35µM), Aß25-35 plus ULMWH (2, 10, 50 µg/ml) or LMWH (10 µg/ml) for 24h. The cell viability was assessed by MTT and LDH release. FITC-Annexin V/PI double staining, Hoechst 33258 staining, TUNEL and Western blotting for bcl-2 and caspase-3 were employed to measure the neuron apoptosis. Furthermore, the intracellular Ca(2+) concentration was measured by a fluorescent dye, Fura-2/AM. The results showed that ULMWH significantly increased cell viability and the protein expression levels of bcl-2 and decreased the LDH release, the number of apoptotic cells, the concentration of intracellular Ca(2+) and the protein expression levels of caspase-3 in cortical neurons, suggesting that ULMWH can obviously reduce Aß25-35-induced neurotoxic effects and might act as a potential agent for Alzheimer's disease.

Protective effect of ultra low molecular weight heparin on glutamate-induced apoptosis in cortical cells.

PURPOSE: To investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms. MATERIALS AND METHODS: Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca(2+)](i)) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot. RESULTS: Typical apoptotic morphological change in rat cortical cells treated with 100 micromol/L glutamate for 24h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca(2+)](i), down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate-induced apoptosis, attenuate the increase of [Ca(2+)](i) not only in medium containing Ca(2+) but also in Ca(2+)-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation. CONCLUSION: ULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca(2+) release and modulation of apoptotic processes.

Antagonistic effects of ultra-low-molecular-weight heparin against cerebral ischemia/reperfusion injury in rats.

Heparin and low-molecular-weight heparin have long been proposed for stroke treatment. This study was conducted to demonstrate the antagonistic effects of ultra-low-molecular-weight heparin (ULMWH) on cerebral ischemic injury in rats and the mechanisms underlying the effects. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion for 24h. ULMWH (0.5, 1 mg kg(-1), i.v.) was administered after the MCAO and reperfusion. Twenty-four hours after the reperfusion, neurological deficit scores, body weight and infarct volume were assessed. Spectrophotometric assay was used to determine the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) of the brain. Furthermore, the intracellular Ca(2+) concentration ([Ca(2+)]i) was measured. The results showed that vein injection of ULMWH at doses of 0.5 and 1.0 mg kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, reducing the infarct volume. At the same time, ULMWH significantly decreased MDA content, and increased SOD activity in ischemic brain. Compared with model group, ULMWH decreased the intracellular calcium concentration remarkably. All these findings suggest that ultra-low-molecular-weight heparin might act as a neuroprotective agent useful in the treatment in focal cerebral ischemia.

Identification and characterization of a neutralizing monoclonal antibody for the epitope on HM-1 killer toxin.

Killer toxin-neutralizing monoclonal antibody (nmAb-KT) against HM-1 killer toxin (HM-1) produced by yeast Williopsis saturnus var. mrakii IFO 0895 reduces both the killing and glucan synthase inhibitory activity of HM-1. nmAb-KT is classified as IgG1kappa and has been shown to be ineffective against HYI killer toxin produced by the related yeast W. saturnus var. saturnus IFO 0117. To determine the epitope for nmAb-KT, overlapping peptides were synthesized from the primary structure of HM-1. nmAb-KT reacted with peptides P5 (33NVHWMVTGGST43), P6 (39TGGSTDGKQG48) and P7 (44DGKQGCATIWEGS56), which represent the middle region of the HM-1 sequence. P6 reacted most strongly with nmAb-KT. Combined analysis by immunoblotting, surface plasmon resonance (SPR) analysis and yeast growth inhibition assay showed that nmAb-KT recognizes a specific epitope within peptide P6. The K(d) value of nmAb-KT against HM-1 and P6 were determined to be 5.48 x 10(-9) M and 1.47 x 10(-6) M by SPR analysis, respectively. These results strongly indicate that nmAb-KT binds to HM-1 at the sequence 41GSTDGK46, and not to HYI at the same position. The potential active site of HM-1 involved in the killing activity against sensitive yeast is discussed.

Beneficial effects of melatonin in experimental models of Alzheimer disease.

Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxidant and free radical scavenger. Additionally, melatonin stimulates several antioxidative enzymes and improves mitochondrial energy metabolism. These findings led us to study amyloid precursor protein transgenic mice, ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe whether melatonin had any effect on Alzheimer's symptoms or pathological changes. We found that melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of beta-amyloid (Abeta) deposition and Abeta fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation. These actions may potentially slow down or stop the progression of dementia.

Monoclonal antibodies and sandwich ELISA for quantitation of HM-1 killer toxin.

To establish a method for quantitative analysis of HM-1 killer toxin (HM-1), two purified mouse monoclonal antibodies, 1F1 and 4A2, and rabbit polyclonal antiserum against HM-1 were prepared. Both monoclonal antibodies were classified as IgG1(kappa) subtype, and did not neutralize the killing activity of HM-1. By SPOTs analysis, the epitope of 1F1 was found in the sequence of CDPNTG with a corresponding sequence of 11-16 from N-terminal amino acid residues of HM-1, but the epitope of 4A2 was not determined. Using 4A2 and polyclonal antiserum, the sandwich enzyme-linked immunosorbent assay (ELISA) was applied to establish the quantitative determination of HM-1. The concentration of HM-1 was determined successfully at the range of 2.5-100 ng/ml. But in the case of 1F1, the method was not established. Genes were constructed to apply the system to the measurement of the secreted concentrations of mutant HM-1, and it was evident that the production of mutant toxins varied among HM-1 mutant genes. The findings of this study are unique in determinimg the epitope of monoclonal antibody against HM-1, and in quantifying the HM-1 using the spot analysis and sandwich ELISA methods.

Effects of diacetyl guan-fu base A on pacemaker cells in sinoatrial node of rabbits.

AIM: To study the electrophysiological effects of diacetyl guan-fu base A (DGFA) on pacemaker cells in sinoatrial (SA) node. METHODS: Intracellular microelectrode method was used to record parameters of action potential (AP) in SA node of rabbits. RESULTS: DGFA could not only slow down spontaneous firing frequency (SFF), mean rate of repolarization (MRR), and rate of diastolic depolarization (RDD), but also prolong diastolic interval (DI) and duration of action potential (APD) in a concentration-dependent manner in SA node. Furthermore, DGFA markedly decreased the maximum rate of depolarization (MRD) with a slight reduce of the amplitude of action potential (APA) and there was no significant effect on the maximal diastolic potential (MDP). The decrease in SFF caused by DGFA was not affected by atropine (0.05 mg/L). CONCLUSION: The effects might be due to the reduction of calcium influx and potassium efflux, and the muscarinic receptors were not involved.