Research on the 3D Reverse Time Migration Technique for Internal Defects Imaging and Sensor Settings of Pressure Pipelines.

Although pressure pipelines serve as a secure and energy-efficient means of transporting oil, gas, and chemicals, they are susceptible to fatigue cracks over extended periods of cyclic loading due to the challenging operational conditions. Their quality and efficiency directly affect the safe operation of the project. Therefore, a thorough and precise characterization approach towards pressure pipelines can proactively mitigate safety risks and yield substantial economic and societal benefits. At present, the current mainstream 2D ultrasound imaging technology faces challenges in fully visualizing the internal defects and topography of pressure pipelines. Reverse time migration (RTM), widely employed in geophysical exploration, has the capability to visualize intricate geological structures. In this paper, we introduced the RTM into the realm of ultrasonic non-destructive testing, and proposed a 3D ultrasonic RTM imaging method for internal defects and sensor settings of pressure pipelines. To accurately simulate the extrapolation of wave field in 3D pressure pipelines, we set the absorbing boundary and double free boundary in cylindrical coordinates. Subsequently, using the 3D ultrasonic RTM approach, we attained higher-precision 3D imaging of internal defects in the pressure pipelines through suppressing imaging artifacts. By comparing and analyzing the imaging results of different sensor settings, the design of the observation system is optimized to provide a basis for the imaging and interpretation of actual data. Both simulations and actual field data demonstrate that our approach delivers top-notch 3D imaging of pipeline defects (with an imaging range accuracy up to 97.85%). This method takes into consideration the complexities of multiple scattering and mode conversions occurring at the base of the defects as well as the optimal sensor settings.

Transcriptome Analysis and Functional Validation Identify a Putative bZIP Transcription Factor, Fpkapc, that Regulates Development, Stress Responses, and Virulence in Fusarium pseudograminearum.

Fusarium pseudograminearum is a soilborne, hemibiotrophic phytopathogenic fungus that causes Fusarium crown rot and Fusarium head blight in wheat. The basic leucine zipper proteins (bZIPs) are evolutionarily conserved transcription factors that play crucial roles in a range of growth and developmental processes and the responses to biotic and abiotic stresses. However, the roles of bZIP transcription factors remains unknown in F. pseudograminearum. In this study, a bZIP transcription factor Fpkapc was identified to localize to the nucleus in F. pseudograminearum. A mutant strain (Δfpkapc) was constructed to determine the role of Fpkapc in growth and pathogenicity of F. pseudograminearum. Transcriptomic analyses revealed that many genes involved in basic metabolism and oxidation-reduction processes were downregulated, whereas many genes involved in metal iron binding were upregulated in the Δfpkapc strain, compared with the wild type (WT). Correspondingly, the mutant had severe growth defects and displayed abnormal hyphal tips. Conidiation in the Fpkapc mutant was reduced, with more conidia in smaller size and fewer septa than in the WT. Also, relative to WT, the Δfpkapc strain showed greater tolerance to ion stress, but decreased tolerance to H2O2. The mutant caused smaller disease lesions on wheat and barley plants, but significantly increased TRI gene expression, compared with the WT. In summary, Fpkapc plays multiple roles in governing growth, development, stress responses, and virulence in F. pseudograminearum.

Ozone causes depressive-like response through PI3K/Akt/GSK3ß pathway modulating synaptic plasticity in young rats.

Ozone pollution has been associated with several adverse effects, including memory impairment, intellectual retardation, emotional disturbances. However, the potential mechanisms remain uncertain. The present study aimed to investigate whether ozone (O3) regulates synaptic plasticity through PI3K/Akt/GSK3ß signaling pathway and induces neurobehavioral modifications among the young rats. In vivo, the newborn rats were used to construct the animal model of early postnatal O3 treatment. In vitro, this study measured the effect of different concentrations of serum from O3 treated rats on the viability of the PC12 cells, and investigated the modifications of synaptic plasticity and PI3K/Akt/GSK3ß signaling pathway in the hippocampus and PC12 cells after O3 treated. The results revealed significant depression-like behavior and increased hippocampal histopathological damage in the young rats after O3 treated. Compared with the control group, the expression levels of synaptic related proteins including Drebrin, PSD95, Synaptophysin and PIK3R1, p-Akt, and p-GSK3ß were decreased in the O3 treated group. In vitro assays, a significant reduction in Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß was found in PC12 cells after O3 serum treated. While 740Y-P (a specific PI3K activator) administered, the expression levels of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in the 740Y-P + O3 group were significantly elevated in vivo and vitro compared with the O3-only group. In addition, miRNAs modulating PIK3R1 were screened on bioinformatics website, the study found aberrant expression of miR-221-3p in the hippocampus and serum of O3 treated group. Inhibition of miR-221-3p expression effectively reversed the reduction of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in PC12 cells induced by O3 treatment. Altogether, these studies indicate that O3 restrained the expression of PI3K/Akt/GSK3ß signaling pathway and impaired synaptic plasticity that resulted in depressive-like behavior in young rats. Moreover, miR-221-3p plays an important role in this procedure by regulating PIK3R1.

JAK2/STAT3 pathway regulates microglia polarization involved in hippocampal inflammatory damage due to acute paraquat exposure.

OBJECTIVE: To explore the effects of acute paraquat (PQ) exposure on the phenotypic polarization of hippocampal microglia and its mechanism. METHODS: An acute PQ exposure rat model was established. Male SD rats were exposed to 0, 5, 25, and 50 mg/kg PQ, and brain hippocampal tissue was collected after 1, 3, and 7 days of exposure, respectively. Hippocampal pathological changes were examined by H&E staining, and immunohistochemistry (IHC) was used to detect changes in the number of Iba-1-positive cells, the average number of endpoints, and the average process length. The protein expression of Iba-1 was detected by western blotting. BV-2 microglia were treated with 0, 0.01, 0.025, 0.05, or 0.1 µmol/L PQ for 24 h. ELISA and western blotting assays were performed to detect the expression of TNF-α and IL-1ß in vivo and in vitro. The M1 microglia marker iNOS, the M2 microglia marker Arg-1, and the p-JAK2 and p-STAT3 protein were detected by western blotting. JAK2/STAT3 pathway activation role in regulating microglia phenotypic polarization was further validated in vivo and in vitro by JAK2-specific inhibitor AG490 administration. RESULTS: After acute PQ exposure, hippocampal neurons showed pathological changes such as loose arrangement and nuclear pyknosis, the number of Iba-1 positive cells and the expression of Iba-1 protein increased, and the average number of endpoints and average process length of microglia decreased. Histological examination revealed that compared with the control group, in the 50 mg/kg PQ group on the 3rd and 7th day, the expression of TNF-α, IL-1ß, and iNOS significantly increased, while that of Arg-1 significantly decreased. p-JAK2 and p-STAT3 expression significantly increased in the 50 mg/kg PQ group on the 1st, 3rd, and 7th day. In vitro, compared with the control group, the expression of TNF-α, IL-1ß, iNOS, p-JAK2, and p-STAT3 significantly increased, while Arg-1 expression was significantly reduced in the 0.025, 0.05, and 0.1 µmol/L PQ groups. After AG490 administration, the expression levels of p-JAK2, p-STAT3, iNOS, TNF-α, and IL-1ß in the AG490 +PQ group were significantly inhibited in vivo and in vitro compared with the PQ-only group. On the contrary, Arg-1 expression was significantly increased. CONCLUSION: Our results suggest that acute PQ exposure may induce M1-type polarization of hippocampal microglia by activating the JAK2/STAT3 pathway, which in turn releases pro-inflammatory factors such as TNF-α and IL-1ß, leading to hippocampal inflammatory damage.

Leveraging Wearable Sensors for Human Daily Activity Recognition with Stacked Denoising Autoencoders.

Activity recognition has received considerable attention in many research fields, such as industrial and healthcare fields. However, many researches about activity recognition have focused on static activities and dynamic activities in current literature, while, the transitional activities, such as stand-to-sit and sit-to-stand, are more difficult to recognize than both of them. Consider that it may be important in real applications. Thus, a novel framework is proposed in this paper to recognize static activities, dynamic activities, and transitional activities by utilizing stacked denoising autoencoders (SDAE), which is able to extract features automatically as a deep learning model rather than utilize manual features extracted by conventional machine learning methods. Moreover, the resampling technique (random oversampling) is used to improve problem of unbalanced samples due to relatively short duration characteristic of transitional activity. The experiment protocol is designed to collect twelve daily activities (three types) by using wearable sensors from 10 adults in smart lab of Ulster University, the experiment results show the significant performance on transitional activity recognition and achieve the overall accuracy of 94.88% on three types of activities. The results obtained by comparing with other methods and performances on other three public datasets verify the feasibility and priority of our framework. This paper also explores the effect of multiple sensors (accelerometer and gyroscope) to determine the optimal combination for activity recognition.

Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma.

BACKGROUND: Complement C3 has been shown to be highly expressed in cutaneous squamous cell carcinoma (cSCC) tumour tissues and is correlated with tumour cell growth. This study aimed to investigate the mechanism of C3 in cSCC malignant transformation. METHODS: C3 expression was analysed in cSCC cell lines A431, Tca8113, SCC13, HSC-5 and HSC-1 and in immortalized HaCaT keratinocytes. Proliferation and migration of cSCC were determined after C3a exposure. Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), pro-matrix metalloproteinase 1 (pro-MMP1), pro-matrix metalloproteinase 2 (pro-MMP2), stemness factors, GSK-3ß, and ß-catenin were analyzed. Tumour growth was examined in a murine xenograft model. RESULTS: C3 expression was much more highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment significantly promoted cSCC cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro-MMP1 and pro-MMP2 expression, which were impeded by the C3aR antagonist. Moreover, the expression of stemness factors Sox-2, Nanog, Oct-4, c-Myc and CD-44 was stimulated by C3a and slowed by C3aR disruption. Knockdown of Sox-2 by siRNA transfection suppressed cell proliferation and migration, constrained VEGF secretion and inhibited pro-MMP1 and pro-MMP2 expression. C3a also activated the Wnt and ß-catenin pathway in cSCC cells. Disruption of C3aR expression dampened tumour growth and the expression of Wnt-1, ß-catenin and Sox-2 in the xenograft model. CONCLUSIONS: C3a enhanced cell proliferation, migration and stemness in cSCC, and this activity was correlated with activation of the Wnt and ß-catenin pathway.

[Pollution level and health risk assessment of heavy metals and hazardous elements in Bombyx Batryticatus].

In order to comprehensively analyze the pollution level and bioaccessibility of different types of heavy metals and hazardous elements in animal medicine,this paper selected Bombyx Batryticatus as the research object,and used inductively coupled plasma mass spectrometry( ICP-MS) to detect As,Cu,Hg,Pb,Ni,Cr,Zn and Cd. Based on the artificial gastrointestinal digestion model and the health risk assessment model of Chinese medicinal materials,the pollution level,in vivo and in vitro transfer rate and health risk grade of eight harmful elements in the above-mentioned medicinal materials of Bombyx Batryticatus were obtained respectively. The test result was found that under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 50% for Bombyx Batryticatus,which including 2 batches of As and 4 batches of Cr exceeded the MRL. In artificial gastrointestinal digestion solution,the transfer rates of heavy metals As,Cu,Hg,Pb,Ni,Cr,Zn and Cd were 36. 849%,72. 372%,41. 152%,75. 354%,46. 603%,27. 981%,19. 707% and 76. 282%,respectively. The data of risk assessment model showed that the total THQ values of the most polluted batches for adults and children was 0. 021 548 and 0. 018 418,respectively. After digestion,the THQ values decreased to 0. 012 599 for adults and 0. 010 769 for children,which were still higher than the THQ standard values of animal medicine Bombyx Batryticatus. However,the CR value of carcinogenic risk is less than 1×10-6,so the potential non-carcinogenic risk caused by taking this batch of Bombyx Batryticatus medicines is higher and the carcinogenic risk can be ignored. To sum up,heavy metals and hazardous elements in Bombyx Batryticatus still exceed the standard,but the health risk level caused by heavy metals still needs to be investigated according to different medicinal materials,in order to provide data support for further improving the quality and safety of animal medicine.

[Determination of arsenic speciation in 17 commonly used traditional Chinese herbal medicines by HPLC-ICP-MS].

The element speciation analysis for heavy metals in herbal medicines is still in the beginning stage. In this study,the total amount of arsenic( As) in 103 batches of 17 commonly used Chinese medicines( including 16 plant medicines and 1 medicinal fungus) was detected by inductively coupled plasma mass spectrometry( ICP-MS). Furthermore,based on HPLC-ICP-MS,the simultaneous detection methods of six As speciation kinds in traditional Chinese medicines were established. An AS7 anion exchange column was selected and the As forms in 17 traditional Chinese medicines was systematically analyzed. The results showed that the method of pretreatment of medicinal materials by microwave digestion and the detection of total amount of As by ICP-MS was stable and reliable. As for the speciation analysis of As,the high-speed ultrasonic extraction method was adopted,and it showed that the linear relationship of the six As speciation was satisfied with the correlation coefficient R2>0. 999 9. The LOQ of six kinds of As speciation were 0. 20,0. 10,0. 15,0. 10,0. 25,0. 10 µg·L~(-1) for arsenic betaine( As B),arsenious acid [As( Ⅲ) ],dimethyl arsenic( DMA),arsenic choline( As C),monomethyl arsenic( MMA),arsenic acid[As( Ⅴ) ],respectively. The recoveries were between 84. 24% and 121. 5%,and the relative standard deviations were 2. 7% to 11%. Among the 103 batches of medicinal materials,only one batch of sample As exceeded the Chinese Pharmacopoeia limit standard; As( Ⅲ) and As( Ⅴ) had high detection rate in 103 batches of Chinese herbal medicines,within which As( Ⅴ) was the main detected form,and inorganic As accounted for the ratio reached 80. 90%-98. 73%; some samples detected DMA,MMA and As B,As C was not detected in any batch. This study established an analytical method suitable for the speciation of As in Chinese herbal medicines,and provided basic data for As residual residue in Chinese herbal medicines,which can provide important reference for the risk assessment and quality standards.

[Safety evaluation of heavy metals contaminated Astragalus membranaceus using health risk assessment model].

To evaluate the safety of heavy metals contaminated Astragalus membranaceus,an appropriate protocol was established to study the heavy metals pollution level by health risk assessment. This study provided a detailed procedure to assess the medicinal herbs in quality control and safety evaluation,and expected to create awareness among the public on the safety of consuming of A. membranaceus or any other kinds of medicinal herbs. The heavy metals content of Cu,As,Cd,Pb and Hg in a total of 45 batches of A. membranaceus were carefully analyzed with a developed inductively coupled plasma mass spectrometry( ICP-MS). Besides,the heavy metal contamination level was further evaluated through 4 main assessment parameters,including maximum residue limit( MRL) set by International Standard Organization,estimated daily intake( EDI) set by IUPAC,target hazard quotients( THQ) and Total THQ set by USEPA and total THQs in raw herbs of A. membranaceus. In addition,the recommended MRLs of 5 main heavy metals aimed to A. membranaceus were calculated based on the regulated consumption quantity. The result showed that,under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 8. 89% for A. membranaceus,which including 4 batches of A. membranaceus exceeded the MRL of As. Here,the standard THQ value of A. membranaceus was firstly proposed as 0. 02 and 0. 011 25 for adults and children,respectively,which were calculated with the recommended consumption quantity of 30 g and 9 g for adults and children. Furthermore,the values of THQ for As and total THQs in adults and children were exceeded the standard THQ in A. membranaceus,and the recommended MRLs of Pb,Cd,Hg and Cu in above medicinal materials that calculated based on health risk assessment model were higher than the regulated MRLs that set by ISO and Chinese Pharmacopeia. The research showed that the contents of heavy metals in A. membranaceus were not in the safe range and the certain non-carcinogenic risks to human body cannot be neglected. Based on above investigation result,it is easily known that the common evaluation method for raw herbs based on the comparison of MRL of heavy metals was not precise enough,and the international model of health risk assessment should be built for each medicinal herb. Above all,this study provided a more realistic research approach for safety evaluation of any other kinds of heavy metals contaminated medicinal herbs,including the establishment of heavy metals standard limit in a specified medicinal herb under recommended consumption quantity,and it is expected to create awareness among the public on the safety of consuming any other medicinal herbs.

Topovectorial mechanisms control the juxtamembrane proteolytic processing of Nrf1 to remove its N-terminal polypeptides during maturation of the CNC-bZIP factor.

The topobiological behaviour of Nrf1 dictates its post-translational modification and its ability to transactivate target genes. Here, we have elucidated that topovectorial mechanisms control the juxtamembrane processing of Nrf1 on the cyto/nucleoplasmic side of endoplasmic reticulum (ER), whereupon it is cleaved and degraded to remove various lengths of its N-terminal domain (NTD, also refolded into a UBL module) and acidic domain-1 (AD1) to yield multiple isoforms. Notably, an N-terminal ~12.5-kDa polypeptide of Nrf1 arises from selective cleavage at an NHB2-adjoining region within NTD, whilst other longer UBL-containing isoforms may arise from proteolytic processing of the protein within AD1 around PEST1 and Neh2L degrons. The susceptibility of Nrf1 to proteolysis is determined by dynamic repositioning of potential UBL-adjacent degrons and cleavage sites from the ER lumen through p97-driven retrotranslocation and -independent pathways into the cyto/nucleoplasm. These repositioned degrons and cleavage sites within NTD and AD1 of Nrf1 are coming into their bona fide functionality, thereby enabling it to be selectively processed by cytosolic DDI-1/2 proteases and also partiality degraded via 26S proteasomes. The resultant proteolytic processing of Nrf1 gives rise to a mature ~85-kDa CNC-bZIP transcription factor, which regulates transcriptional expression of cognate target genes. Furthermore, putative ubiquitination of Nrf1 is not a prerequisite necessary for involvement of p97 in the client processing. Overall, the regulated juxtamembrane proteolysis (RJP) of Nrf1, though occurring in close proximity to the ER, is distinctive from the mechanism that regulates the intramembrane proteolytic (RIP) processing of ATF6 and SREBP1.

[Research progress of chromium and its speciation analysis].

Chromium has been discovered for more than two hundred years, and it has advantages of wear-resisting, high temperature, corrosion resistance and so on. Chromium has been widely used in industrial production and received extensive attention in China and abroad. Detailed limit standards have been set for chromium in food and fishery product, and chromium can also be enriched in many traditional Chinese medicines. Besides, the toxicities of different chromium speciation are quite different, and thus morphological analysis is necessary. However, the transformation or migration is easily happened among different speciation which brings difficulties to research and analysis. This article summarizes the research status of chromium and its aims to provide reference for scientific research and pollution prevention of chromium.

R- and S-terbutaline activate large conductance and Ca2+ dependent K+ (BKCa) channel through interacting with ß2 and M receptor respectively.

This study investigated the effect of the ß2 receptor agonist terbutaline on the single channel activity of BKCa channel. The effects of racemate and two isomers of terbutaline were all assessed. ß2 adrenoceptors were stably overexpressed on HEK293 cells by lentiviral transduction method and chicken BKCa channels were transiently expressed on normal HEK293 cell line or HEK293 cells overexpressing ß2 receptors. Data showed that terbutaline significantly increased the single channel open probability of BKCa channel within 10min. The channel activating effects of terbutaline are stereoselective and mainly stay with the R-enantiomers. The opening probability of BKCa channel at 10min after drug application normalized to that just before drug application (Po10/Po0s) for R- and S-terbutaline were 7.85±3.20 and 1.06±0.45 respectively at 1µM concentration, corresponding to 28.37±9.96 and 2.68±1.09 at the higher concentration of 10µM. ICI 118551 blocked the effect of R- but not S-terbutaline (10µM), whereas atropine blocked the channel activating effects of S-terbutaline of higher concentration. In addition, the muscarinic receptor agonist carbachol increased the BKCa channel activity in an atropine-sensitive manner as an positive control experiment, which indicate the involvement of M receptor in the channel activating effect of S-terbutaline.

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of Ito is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for Ito and ICaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of Ito and ICaL are correlated to the alterations of the mRNA transcription level.

Inhibition of rapid delayed rectifier potassium current (IKr) by ischemia/reperfusion and its recovery by vitamin E in ventricular myocytes.

Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium (IKr) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of IKr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na2S2O4) in ventricular myocytes of guinea pigs. The IKr current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of IKr is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100µmol/L). The value of IKr tail current density increased from 0.516±0.040 pA/pF in I/R to 0.939±0.091 pA/pF when treated with vitamin E. Moreover, we also demonstrated that QTc interval was increased by I/R and reversed by Vitamin E in isolated guinea pig hearts. In conclusion, the inhibition of IKr is one of the underlying mechanisms of prolongation of QT interval and APD in I/R. Vitamin E might have a benefit in coronary reperfusion therapy.

[Advances on nanoparticles-tagged visual test strips for the rapid detection of pesticides].

The residue of the pesticides affects seriously the quality and safety of traditional Chinese medicine. Pesticide residue has caused ever-growing attention of people at home and abroad. Rapid detection techniques used for rapid screening of pesticide residues have expanded in a fast progress. As one of the fast development methods of rapid detection, visualization test strip based on nanoparticle has received much concern in recent years. This article focused on the classification of detection test strips and key factors on the fabrication of nanoparticle-based visualization test strips used in small molecule pesticides. Moreover, a wide application of nanoparticles-tagged test strips on pesticide residue was reviewed including single residue detection, multi residue detection, as well as quantitative analysis. Finally, the future application of visual test strip for detecting of pesticide residues in traditional Chinese medicine was forecasted, intending to provide the reference for rapid detection techniques on pesticide residues screening in herbal medicine industry.

[Research progresses and formulation development of natural anti-mildew agents based on Chinese herbal medicines].

Owing to the intrinsic factors and some extrinsic environmental conditions, many foods, agricultural products and Chinese materia medicas (CMMs), if not handled properly in the processes of growth, harvesting, processing and storage, can be easily contaminated by all kinds of molds to produce mycotoxins of serious toxicity, which will not only affect the quality, safety and effectiveness of CMMs, but also result in potential threatens to human and animal's health and life. Therefore, in recent decades, it has become the focus on how to prevent and control the foods, agricultural products and CMMs from being moldy and producing toxicity for scientific preservation. Many Chinese herbal medicines (CHMs) especially those with high content of volatile oils with strong antifungal activities have been applied for the scientific preservation of foods, agricultural products and CMMs. Based on these situations, natural anti-mildew agents have been further developed and made into some useful dosage forms, such as tablets, aerosol, liposomes and inclusion, which will not only greatly expand the application scope of CHMs to make the use of anti-mildew agents more convenient, but also achieve the sustained or controlled release of the antifungal effect for scientific preservation of foods, agricultural products and CMMs.

[In vitro effect and mechanistic study of compound E23869 on lipid metabolism].

This study was designed to identify inducers of ATP-binding cassette transporter A1(ABCA1) and CD36 and lysosomal integral membrane protein-II analogous-1(CLA-1) and to evaluate the in vitro effect of the active compound on lipid metabolism. Among 20 000 compounds screened, E23869 was found as a positive hit using cell-based high throughput screening models. The up-regulating activities of E23869 in ABCA1p-LUC and CLA-1p-LUC Hep G2 cells were 196% and 198%, respectively. The EC(50) values of E23869 in ABCA1p- LUC and CLA-1p-LUC Hep G2 cells were 0.25 µmol·L(-1) and 0.66 µmol·L(-1), respectively. E23869 significantly upregulated the protein levels of ABCA1, scavenger receptor class B type I(SR-BI)/CLA-1 and ATP-binding cassette transporter G1(ABCG1) in both macrophages RAW264.7 and L02 cells by Western blotting analysis. Foam cell assay showed that E23869 inhibited lipids accumulations in macrophages RAW264.7. Cholesterol efflux assay showed that E23869 induced HDL-mediated cholesterol efflux in macrophages RAW264.7. Moreover, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions through activation of PPARα and PPARγ. In addition, E23869 weakly promoted in vitro differentiation of mouse preadipocytes 3T3-L1. In conclusion, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions to promote cholesterol efflux, which is a good leading compound for regulation of lipid metabolism.

Effect of inserting charged peptide at NH(2)-terminal on N-type inactivation of Kv1.4 channel.

Rapid inactivation of voltage-gated potassium channel plays an important role in shaping the electrical signaling in neurons and other excitable cells. N-type ("ball and chain") inactivation, as the most extensively studied inactivation model, is assumed to be the inactivation mechanism of Kv1.4 channel. The inactivation ball inactivates the channel by interacting with the hydrophobic wall of inner pore and occluding it. Recently, we have proved that the electrostatic interaction between two charged segments in the NH(2)-termainal plays an important role through promoting the inactivation process of the Kv1.4 channel. This study investigates the effect of inserting negatively or positively charged short peptides at NH(2)-terminal on the inactivation of Kv1.4 channel. The results that inserting negatively-charged peptide (either myc or D-peptide) at different sites of NH(2)-terminal, deceleraes inactivation process of Kv1.4 channel to a different extent with inserting site changing and that the mutant Kv1.4-D50 exhibits a more slower inactivation rate than Kv1.4-K50 further identified the role of electrostatic interactions in the "ball and chain" inactivation mechanism.

Electrostatic interaction between inactivation ball and T1-S1 linker region of Kv1.4 channel.

Inactivation of potassium channels plays an important role in shaping the electrical signaling properties of nerve and muscle cells. The rapid inactivation of Kv1.4 has been assumed to be controlled by a "ball and chain" inactivation mechanism. Besides hydrophobic interaction between inactivation ball and the channel's inner pore, the electrostatic interaction has also been proved to participate in the "ball and chain" inactivation process of Kv1.4 channel. Based on the crystal structure of Kv1.2 channel, the acidic T1-S1 linker is indicated to be a candidate interacting with the positively charged hydrophilic region of the inactivation domain. In this study, through mutating the charged residues to amino acids of opposite polar, we identified the electrostatic interaction between the inactivation ball and the T1-S1 linker region of Kv1.4 channel. Inserting negatively charged peptide at the amino terminal of Kv1.4 channel further confirmed the electrostatic interaction between the two regions.

Water security assessment and driving mechanism in the ecosystem service flow condition.

Water resources are the foundation of human survival and development. Thus, it is essential to quantify the relationship between water supply and demand and assess water security to ensure sustainable use of water resources. In this study, we quantified the relationship between water supply and demand in the Yiluo River Basin (YRB) using the InVEST model, constructed a spatial flow model of water provision service at the sub-watershed scale, and analyzed the water security index (WSI) under static and dynamic conditions. Subsequently, we used geographic detectors to identify the explanatory power of the main influencing factors of the WSI. The results showed that (1) from 2005 to 2018, the water supply decreased continuously and the water demand first increased and then decreased in the YRB; (2) the spatial pattern of WSI showed that it was high in the southwest and low in the northeast, wherein the highest and lowest WSI values occurred in 2005 and 2018, respectively. From 2005 to 2018, the mean values of the static and dynamic WSI decreased from 0.77 to 0.60 and 1.56 to 1.20, respectively. (3) The precipitation factor from the supply dimension and the gross domestic product (GDP) factor from the demand dimension had the strongest explanatory power for the static WSI. For the dynamic WSI, the flow quantity of the water provision service flow had the strongest explanatory power. This study provided a reference for governments to formulate sustainable water resource management.