Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury.

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.

Performance evaluation of the UV activated chlorite process on trimethoprim: Degradation efficiency, energy consumption and disinfection by-products formation.

As the primary inorganic by-product species of ClO2, chlorite is believed to have negative toxicological effects on human health and therefrom greatly limits the wide application of ClO2 in water treatment. The synergistic trimethoprim (TMP) removal concerning degradation efficiency, energy consumption and disinfection by-products (DBPs) formation in the UV activated chlorite process accompanied by the simultaneously elimination of chlorite was comprehensively evaluated. UV/chlorite integrated process removed TMP far more rapidly than UV (1.52%) or chlorite (3.20%) alone due to the endogenous radicals (Cl•, ClO• and •OH), the contributing proportions of which were 31.96%, 19.20% and 44.12%. The second-order rate constants of TMP reaction with Cl•, ClO• and •OH were determined to be 1.75 × 1010, 1.30 × 109 and 8.66 × 109 M-1 s-1. The effects of main water parameters including chlorite dosage, UV intensity, pH as well as water matrixes (nature organic matter, Cl- and HCO3-) were examined. kobs obeyed the order as UV/Cl2>UV/H2O2≈UV/chlorite>UV, and the cost ranking via electrical energy per order (EE/O, kWh m-3 order-1) parameter was UV/chlorite (3.7034) > UV/H2O2 (1.1625) >UV/Cl2 (0.1631). The operational scenarios can be optimized to achieve the maximum removal efficiencies and the minimum energy costs. The destruction mechanisms of TMP were proposed by LC-ESI-MS analysis. The overall weighted toxicity in subsequent disinfection was assessed as UV/Cl2>UV/chlorite > UV, the values of which in post-chlorination were 6.2947, 2.5806 and 1.6267, respectively. Owing to the vital roles of reactive chlorine species (RCS), UV/chlorite displayed far higher TMP degradation efficiency than UV, and concurrently presented much less toxicity than UV/Cl2. In an effort to determine the viability of the promising combination technology, this study was devoted to reduce and reuse chlorite and synchronously realize the contaminants degradation efficiently.

A novel gut-restricted RIPK1 inhibitor, SZ-15, ameliorates DSS-induced ulcerative colitis.

As a key mediator of cell death and inflammation, receptor-interacting protein kinase 1 (RIPK1) responds to a broad set of inflammatory and pro-death stimuli in human diseases. Inhibitors targeting RIPK1 are being investigated for the treatment of a wide range of human diseases, including ulcerative colitis. In the present study, we designed, synthesized, and investigated the anti-necroptosis and RIPK1-inhibition effects of SZ-15-a symmetrical high-molecular-weight (>500 Da) compound. SZ-15 effectively inhibited necroptosis in U937 and HT-29 cells at concentrations of 1 nM and 10 nM, respectively, and SZ-15 at a concentration of 10 nM almost completely blocked RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) protein phosphorylation induced by necrosis inducers. SZ-15 suppressed the pro-necroptosis function of RIPK1 by downregulating the mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. The activities of SZ-15 were effectively restricted to the gut: The percent recovery of the parent form of SZ-15 in mouse feces was 85.75%. Nevertheless, SZ-15 was effectively absorbed and detected in colon tissues after 1 h at a concentration of 3335 ± 868 ng/g, indicating that membrane permeability was maintained. SZ-15 alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in vivo by decreasing TNF-α, IL-1ß, IL-22, and IL-6 mRNA expression in colonic tissues. Our preclinical study describes a novel gut-restricted RIPK1 inhibitor that shows great potential for use in the clinical treatment of ulcerative colitis.

Comparison of UV-induced AOPs (UV/Cl2, UV/NH2Cl, UV/ClO2 and UV/H2O2 ) in the degradation of iopamidol: Kinetics, energy requirements and DBPs-related toxicity in sequential disinfection processes.

The UV-induced advanced oxidation processes (AOPs, including UV/Cl2, UV/NH2Cl, UV/ClO2 and UV/H2O2 ) degradation kinetics and energy requirements of iopamidol as well as DBPs-related toxicity in sequential disinfection were compared in this study. The photodegradation of iopamidol in these processes can be well described by pseudo-first-order model and the removal efficiency ranked in descending order of UV/Cl2  > UV/H2O2  > UV/NH2Cl > UV/ClO2  > UV. The synergistic effects could be attributed to diverse radical species generated in each system. Influencing factors of oxidant dosage, UV intensity, solution pH and water matrixes (Cl- , NH4 + and nature organic matter) were evaluated in detail. Higher oxidant dosages and greater UV intensities led to bigger pseudo-first-order rate constants (Kobs) in these processes, but the pH behaviors exhibited quite differently. The presence of Cl- , NH4 + and nature organic matter posed different effects on the degradation rate. The parameter of electrical energy per order (EE/O) was adopted to evaluate the energy requirements of the tested systems and it followed the trend of UV/ClO2  > UV > UV/NH2Cl > UV/H2O2  > UV/Cl2 . Pretreatment of iopamidol by UV/Cl2 and UV/NH2Cl clearly enhanced the production of classical disinfection by-products (DBPs) and iodo-trihalomethanes (I-THMs) during subsequent oxidation while UV/ClO2 and UV/H2O2 exhibited almost elimination effect. From the perspective of weighted water toxicity, the risk ranking was UV/NH2Cl > UV/Cl2 > UV > UV/H2O2 > UV/ClO2 . Among the discussed UV-driven AOPs, UV/Cl2 was proved to be the most cost-effective one for iopamidol removal while UV/ClO2 displayed overwhelming advantages in regulating the water toxicity associated with DBPs, especially I-THMs. The present results could provide some insights into the application of UV-activated AOPs technologies in tradeoffs between cost-effectiveness assessment and DBPs-related toxicity control of the disinfected waters containing iopamidol.

Prediction of kidney transplant outcome based on different DGF definitions in Chinese deceased donation.

BACKGROUND: Delayed graft function (DGF) is an important complication of kidney transplantation and can be diagnosed according to different definitions. DGF has been suggested to be associated with the long-term outcome of kidney transplantation surgery. However, the best DGF definition for predicting renal transplant outcomes in Chinese donations after cardiac death (DCDs) remains to be determined. METHOD: A total of 372 DCD kidney transplant recipients from June 2013 to July 2017 in the First Affiliated Hospital of Xi'an Jiaotong University were included in this retrospective study to compare 6 different DGF definitions. The relationships of the DGF definitions with transplant outcome were analyzed, including graft loss (GL) and death-censored graft loss (death-censored GL). Renal function indicators, including one-year estimated glomerular filtration rate (eGFR) and three-year eGFR, and were compared between different DGF groups. RESULTS: The incidence of DGF varied from 4.19 to 35.22% according to the different DGF diagnoses. All DGF definitions were significantly associated with three-year GL as well as death-censored GL. DGF based on requirement of hemodialysis within the first week had the best predictive value for GL (AUC 0.77), and DGF based on sCr variation during the first 3 days post-transplant had the best predictive value for three-year death-censored GL (AUC 0.79). Combination of the 48-h sCr reduction ratio and classical DGF can improve the AUC for GL (AUC 0.85) as well as the predictive accuracy for death-censored GL (83.3%). CONCLUSION: DGF was an independent risk factor for poor transplant outcome. The combination of need for hemodialysis within the first week and the 48-h serum creatinine reduction rate has a better predictive value for patient and poor graft outcome.

Generation of functional hepatocyte-like cells from human bone marrow mesenchymal stem cells by overexpression of transcription factor HNF4α and FOXA2.

BACKGROUND: Our previous study showed that overexpression of hepatocyte nuclear factor 4α (HNF4α) could directly promote mesenchymal stem cells (MSCs) to differentiate into hepatocyte-like cells. However, the efficiency of hepatic differentiation remains low. The purpose of our study was to establish an MSC cell line that overexpressed HNF4α and FOXA2 genes to obtain an increased hepatic differentiation efficiency and hepatocyte-like cells with more mature hepatocyte functions. METHODS: Successful establishment of high-level HNF4α and FOXA2 co-overexpression in human induced hepatocyte-like cells (hiHep cells) was verified by flow cytometry, immunofluorescence and RT-PCR. Measurements of albumin (ALB), urea, glucose, indocyanine green (ICG) uptake and release, cytochrome P450 (CYP) activity and gene expression were used to analyze mature hepatic functions of hiHep cells. RESULTS: hiHep cells efficiently express HNF4α and FOXA2 genes and proteins, exhibit typical epithelial morphology and acquire mature hepatocyte-like cell functions, including ALB secretion, urea production, ICG uptake and release, and glycogen storage. hiHep cells can be activated by CYP inducers. The percentage of both ALB and α-1-antitrypsin (AAT)-positive cells was approximately 72.6%. The expression levels of hepatocyte-specific genes (ALB, AAT, and CYP1A1) and liver drug transport-related genes (ABCB1, ABCG2, and SLC22A18) in hiHep cells were significantly higher than those in MSCs-Vector cells. The hiHep cells did not form tumors after subcutaneous xenograft in BALB/c nude mice after 2 months. CONCLUSION: This study provides an accessible, feasible and efficient strategy to generate hiHep cells from MSCs.

Comparison of nighttime and daytime operation on outcomes of kidney transplant with deceased donors: a retrospective analysis.

BACKGROUND: Kidney transplant is always emergent operations and frequently need to be performed at nighttime to reduce cold ischemia time (CIT). Previous studies have revealed that fatigue and sleep deprivation can result in adverse consequences of medical procedures. This study aimed to evaluate whether nighttime operation has adverse impact on kidney transplant. METHODS: A retrospective analysis of recipients accepted kidney transplant from deceased donors in one center from 2014 to 2016 was performed. Daytime transplant was defined as operation started after 8 AM or ended before 8 PM and nighttime operation was defined as operation ended after 8 PM or started before 8 AM. The incidences of complications such as delayed graft function, acute rejection, surgical complications and nosocomial infections were compared between 2 groups. Student's t-test was used to analyze continuous variables such as serum creatinine (Scr) at 1-year of post-transplant. The Chi-square test was used to analyze categorical variables. Differences in recipients and graft survival were analyzed using Kaplan-Meier methodology and log-rank tests. RESULTS: Among the 443 recipients, 233 (52.6%) were classified into the daytime group and the others 210 (47.4%) were in the nighttime group. The 1-year survival rate of recipients was similar for the recipients in the daytime and nighttime groups (95.3% vs. 95.2%, P = 0.981). Although the 1-year graft survival rate in the nighttime group was slightly superior to that in the daytime group, the difference was not significant (92.4% vs. 88.4%, P = 0.164). Furthermore, Scr and incidence of complications were also not significantly different between the 2 groups. CONCLUSIONS: Our results suggested that operation time of kidney transplant with short CIT has no significant impact on the outcome of kidney transplant. Nighttime operation of kidney transplant with short CIT could be postponed to the following day to alleviate the burden on medical staffs and avoid the potential risk.

Photochemical degradation of iodate by UV/H2O2 process: Kinetics, parameters and enhanced formation of iodo-trihalomethanes during chloramination.

In this paper, it was demonstrated that UV/H2O2 process can not only obviously promote the degradation rate of IO3-, but also greatly enhance iodo-trihalomethanes (I-THMs) formation in sequential chloramination. UV/H2O2 exhibited much faster IO3- decomposition than either UV or H2O2 treatment alone due to the contribution of highly reactive species including O-, OH and eaq-. The degradation rate of IO3- was affected by H2O2 dosages, pH, UV intensity as well as the presence of natural organic matter (NOM). The calculated pseudo-first order rate constant gradually increased with H2O2 dosages and solution pH, but behaved directly proportional to the UV intensity. Although NOM remarkably reduced the degradation rate of IO3- in UV/H2O2 process, their presence greatly enhanced the formation of I-THMs during subsequent chloramination. The overwhelming majority of iodoform at high UV fluences was also observed, which indicated improved iodination degrees of the detected I-THMs. UV/H2O2 was proved to be more capable on the evolution of IO3- to I- as well as I-THMs than UV and thereby enhanced the toxicity of disinfected waters in the following chloramination process. This study was among the first to provide a comprehensive understanding on the transformation of IO3- as the emerging iodine precursor to form I-THMs via diverse advanced oxidation process technologies like UV/H2O2.

Predictive Score Model for Delayed Graft Function Based on Hypothermic Machine Perfusion Variables in Kidney Transplantation.

BACKGROUND: Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment. METHODS: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model. RESULTS: HMP duration (OR = 1.165, 95% confidence interval [CI]: 1.008-1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032-10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894-0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0-3, 4-7, 8-11, and 12-14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006). CONCLUSION: The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

A warning for Chinese academic evaluation systems: short-term bibliometric measures misjudge the value of pioneering contributions.

Publication citation-based research evaluation, even if only in support of peer review, is not everywhere, on every level, or for everyone suitable, because of differences in scientific research, patterns of research output, stages of scientific evolution, and merits-scientific or societal-of scientific results.

Heat shock factor C2a serves as a proactive mechanism for heat protection in developing grains in wheat via an ABA-mediated regulatory pathway.

High temperature at grain filling can severely reduce wheat yield. Heat shock factors (Hsfs) are central regulators in heat acclimation. This study investigated the role of TaHsfC2a, a member of the monocot-specific HsfC2 subclass, in the regulation of heat protection genes in Triticum aestivum. Three TaHsfC2a homoeologous genes were highly expressed in wheat grains during grain filling and showed only transient up-regulation in the leaves by heat stress but were markedly up-regulated by drought and abscisic acid (ABA) treatment. Overexpression of TaHsfC2a-B in transgenic wheat resulted in up-regulation of a suite of heat protection genes (e.g. TaHSP70d and TaGalSyn). Most TaHsfC2a-B target genes were heat, drought and ABA inducible. Transactivation analysis of two representative targets (TaHSP70d and TaGalSyn) showed that TaHsfC2a-B activated expression of reporters driven by these target promoters. Promoter mutagenesis analyses revealed that heat shock element is responsible for transactivation by TaHsfC2a-B and heat/drought induction. TaHsfC2a-B-overexpressing wheat showed improved thermotolerance but not dehydration tolerance. Most TaHsfC2a-B target genes were co-up-regulated in developing grains with TaHsfC2a genes. These data suggest that TaHsfC2a-B is a transcriptional activator of heat protection genes and serves as a proactive mechanism for heat protection in developing wheat grains via the ABA-mediated regulatory pathway.

In Vivo Bioluminescence Imaging of Transplanted Mesenchymal Stromal Cells and Their Rejection Mediated by Intrahepatic NK Cells.

PURPOSE: Mesenchymal stromal cells (MSCs) hold promise in the treatment of liver disease. However, short survival time of MSCs after intrahepatic transplantation limits their value; therefore, understanding the basis of MSCs survival and rejection may increase their utility. This study was aimed at determining the role of intrahepatic natural killer (NK) cells on MSCs survival and their retention in the liver shortly after transplant. PROCEDURES: Human MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R), and the residence time and survival of MSCs-R xenografts after intrahepatic transplantation were evaluated by in vivo bioluminescence imaging (BLI). Coculture of MSCs and NK cells was performed to assess cytotoxicity. To evaluate the role of NK cells in rejection of the xenografted cells, the fates of transplanted MSCs-R were then assessed in vivo by BLI after activation of intrahepatic NK cells. RESULTS: We observed a linear correlation between luciferase activity from live MSCs-R and cell number in vitro (R 2 = 0.9956). In vivo, we observed a gradual decline in bioluminescent signals from transplanted MSCs-R over a region corresponding to the liver in both the control group and the NK-activated group. However, the survival time and retention of intrahepatic MSCs-R decreased more rapidly in the NK-activated group of mice compared to the control group. This indicated that activated NK cells accelerate the elimination of transplanted MSCs. Also, we found that the number of hepatic NK cells and the expression of NK activation markers significantly increased after intrahepatic delivery of MSCs. This suggested that resident NK cells, in a resting state, were activated by intrahepatic transplantation of human MSCs. Taken together, the data suggests that activated hepatic NK cells mediate, in part, rejection of the MSCs xenografts. Cytotoxicity assays showed that activated NK cells may inhibit the proliferation of MSCs and, to a certain extent, induce MSCs death. CONCLUSION: Human MSCs could be followed dynamically in vivo by BLI, and the role of murine hepatic NK cells, especially activated NK cells, could be inferred from the loss of signals from MSCs. This finding may have practical clinical implications in MSCs transplantation in treating liver disease.

Phototransformation of iodate by UV irradiation: Kinetics and iodinated trihalomethane formation during subsequent chlor(am)ination.

The photodegradation of IO3- at 254nm and the formation of iodinated trihalomethanes (I-THMs) during subsequent chlorination or chloramination in the presence of natural organic matter (NOM) were investigated in this study. The thermodynamically stable IO3- can be degraded by UV irradiation with pseudo-first order kinetics and the quantum yield was calculated as 0.0591moleinstein-1. Solution pH posed no remarkable influence on the photolysis rate of IO3-. The UV phototransformation of IO3- was evidenced by the determination of iodide (I-) and hypoiodous acid (HOI) in solution. NOM sources not only enhanced the photodegradation rate of IO3- by photoejecting solvated electrons, but also greatly influenced the production I-THMs in subsequent chlor(am)ination processes. In UV irradiation and sequential oxidation processes by chlorine or chloramine, the I-THMs formation was susceptible to NOM sources, especially the two major fractions of aqueous humic substances (humic acid and fulvic acid). The toxicity of disinfected waters greatly increased in chloramination over chlorination of the UV photodecomposed IO3-, as far more I-THMs especially CHI3, were formed. As "the fourth iodine source" of iodinated disinfection by-products, the occurrence, transportation and fate of IO3- in aquatic environment should be of concern instead of being considered a desired iodine sink.

[The Preparation and Properties Study of Micellar Thiacalixarenes Self-Assembled Fluorescent Chemosensor].

A novel ON-OFF micelle-based fluorescent chemosensor for Cu²âº ions was prepared through the micellar self-assembling in water solutions with p-tert-butylthiacalix[4]arene (TCA) as receptor, perylene as fluorophore and Sodium dodecylbenzenesulphonate (SDBS) as self-assembling template. Several effecting factors, such as the quantities of the receptor TCA, the concentrations of the self-assembling template SDBS, the concentrations of the Cu²âº ions and the co-current metal ions, were investigated for the systematical investigation on the detecting capabilities of the micelle-based fluorescent chemosensor for Cu²âº ions through measuring the quenching of the fluorescent emission of the fluorophore. As the results indicated, when the molar concentration ratio value of the receptor TCA to the fluorophore was equal to 1 000 and the concentrations of the self-assembling template SDBS reached 50 mmol · L⁻¹, the Cu²âº ions could be detected preferably by the prepared micelle-based fluorescent chemosensor. The concentrations of the Cu²âº ions could be almost linearly measured according to the quenching ratios of the fluorescent emission in a certain range of concentration. Furthermore, the detecting capabilities of the micelle-based fluorescent chemosensor for the Cu²âº ions were almost not influenced by the co-existing metal ions such as Pb²âº, Cd²âº, Mn²âº, Na⁺ , K⁺, Ca²âº,Mg2²âº A1l³âº NiZ²âºand Zn2²âºions. The selective detecting capabilities of the obtained micelle-based fluorescent chemose5nor for the Cu²âºions could be mainly attributed to the recognition of the receptor TCA in the surfactant micelle with the Cu2²âºions, and the quenching of the fluorescent emission of the fluorophore was estimated to be based on an intramicellar electron-transfer or energy-transfer mechanism.

[Derivative fluorescence probe recognition results of the light physical mechanism of metal ions].

As people deeply study the electronic spectra of fluorescent compounds and photophysical behavior, enormous progress has been made in the aspect of changes and states of different systems in the use of fluorescent molecules as probes. PTC-DA is a kind of typical fluorescent molecular probe that is highly sensitive and selective in water environment. This paper makes a research on the physical mechanism of light of PTCDA by TDF (Density Functional Theory), calculates the optimal configuration the charge population and excitation spectra of PTCDA molecules under ideal condition and acquires PTCDA fluorescence emission spectra then analyses that PTCDA is a kind of quenching and dual colorimetric signal probe response. Its optical signal response mechanism belongs to ICT (Intramolecular Charge Transfer) mechanism. According to the results, this perylene derivatives is fitted with Cu2+ excited state absorption spectra. Before and after the combination with Cu2+, the peak shape of absorption spectrum is similar. When copper is added, the overall absorption peak position occurred redshift, quenching discoloration happens. By comparing with experimental values, the calculated molecular configuration is reasonable and effective and the peak of excitation spectra is realistic. Analysis shows that: PTCDA molecules divalent copper ions have better fluorescence detection activity, the optical signal response mechanisms are intramolecular charge transfer (ICT) mechanisms. When a molecule receives divalent copper ions, the absorption spectrum peak position redshifts, intramolecular charge transfer direction and intensity changes. There occur both quenching signal and discoloration signal. It is a kind of fluorescent probe material with double quenching and discoloration fluorescent signal, which has great potential for development. This paper makes an early-stage exploration of the physical mechanism of light response mechanism analysis in molecular fluorescent probe field and can be a systematically valuable theoretical reference for this field.

Integrated water resources management and water users' associations in the arid region of northwest China: a case study of farmers' perceptions.

Water scarcity is a critical policy issue in the arid regions of northwest China. The local government has widely adopted integrated water resources management (IWRM), but lacks support from farmers and farm communities. We undertook a case study in the Minqin oasis of northwest China to examine farmers' responses to IWRM and understand why farmer water users' associations (WUAs) are not functioning effectively at the community level. Results of quantitative and qualitative surveys of 392 farmers in 27 administrative villages showed that over 70% of farmers disapprove of the IWRM market-based reforms. In particular, the failure of farmer WUAs can be attributed to overlapping organizational structures between the WUAs and the villagers' committees; mismatches between the organizational scale of the WUAs and practical irrigation management by the farmers themselves; marginalization of rural women in water decision-making processes; and the inflexibility of IWRM implementation. An important policy implication from this study is that rebuilding farmer WUAs is key to overcoming the difficulties of IWRM. The current water governance structure, which is dominated by administrative systems, must be thoroughly reviewed to break the vicious cycle of tension and distrust between farmers and the government.

[A TDDFT study on the photophysical mechanism of optical quenching of a new type fluorescent probe molecule].

3-hydroxyl flavone (3-HF), a typical representative of the second generation new fluorescence molecular probe, was studied by high-accuracy quantum chemical methods, density functional theory (DFT), in the present paper. The photo-physics mechanism of 3-HF as fluorescence molecular probe was studied by the calculation of the optimum geometry structure, charge population and excitation spectrum, in the ideal condition. Then the calculation results were analyzed, and the photo-physics looping graph was plotted for the elucidation of the mechanism. Compared with the experiments, the geometry structure obtained by our calculation is in good agreement, and the errors in the calculated excitation spectrum are in a reasonable limitation. As in this paper, it is only a tentative research work in the field of molecule fluorescence probe with the method of quantum chemistry calculation, and we hope that it could provide systematically valuable theoretical reference in this field in the future.

Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease.

A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aß aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aß aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Generation and neuronal differentiation of induced pluripotent stem cells in Cdyl-/- mice.

Chromodomain on Y-like (CDYL) is a chromodomain protein that has sequence homology to members of the enoyl CoA hydratase family. Although the chromodomain of CDYL has been implicated in chromatin remodeling during mammalian spermatogenesis, the function of the Cdyl gene remains unclear. Recently, induced pluripotent stem cells (iPS cells) have been derived from somatic cells by the forced expression of several transcription factors. iPS cells resemble embryonic stem cells in many respects. Therefore, iPS cells represent a powerful tool for the study of gene function. In this study, we have investigated whether iPS cells derived from Cdyl-/- and Cdyl+/+ fibroblasts have different characteristics. Our results showed that both Cdyl-/- and Cdyl+/+ fibroblasts could be induced to become iPS cells, but the spontaneous neuronal differentiation capacity of Cdyl-/- iPS cells was much greater than that of the Cdyl+/+ iPS cells. These results provide some insight into the molecular function of the Cdyl gene, showing that it inhibited the neuronal differentiation of iPS cells.

α-Glucosidase inhibitors via green pathway: biotransformation for bicoumarins catalyzed by Momordica charantia peroxidase.

Peroxidase extracted from Momordica charantia catalyzed the H(2)O(2)-dependent oxidative coupling of 7-hydroxy-4-methylcoumarin to form four new dimers (1-4) and two known ones (5, 6). The structures, including the absolute configurations of axially chiral compounds, were unambiguously characterized by NMR spectroscopy, online HPLC-CD, and a variety of computational methods. Bioactive experiments demonstrated that compounds 1 and 2 had significant inhibitory effects on yeast α-glucosidase, much better than the controls. Noncompetitive binding mode was found by the graphical analysis of steady-state inhibition data. The mechanism of enzymatic inhibition confirmed in some depth that the inhibitors altered the secondary structure of α-glucosidase by decreasing the α-helix and increasing the ß-sheet content. In summary, bicoumarins 1 and 2 might be exploited as the lead compounds for further research of antidiabetic agents, and this research provided a "green" method to synthesize compounds with the chiral biaryl axis generally calling for multistep reactions in organic chemistry.