Monte Carlo(MC) simulations have been performed to refine the estimation of the correction-toscaling exponent ω in the 2D φ^(4)model,which belongs to one of the most fundamental universality classes.If corrections h...Monte Carlo(MC) simulations have been performed to refine the estimation of the correction-toscaling exponent ω in the 2D φ^(4)model,which belongs to one of the most fundamental universality classes.If corrections have the form ∝ L^(-ω),then we find ω=1.546(30) andω=1.509(14) as the best estimates.These are obtained from the finite-size scaling of the susceptibility data in the range of linear lattice sizes L ∈[128,2048] at the critical value of the Binder cumulant and from the scaling of the corresponding pseudocritical couplings within L∈[64,2048].These values agree with several other MC estimates at the assumption of the power-law corrections and are comparable with the known results of the ε-expansion.In addition,we have tested the consistency with the scaling corrections of the form ∝ L^(-4/3),∝L^(-4/3)In L and ∝L^(-4/3)/ln L,which might be expected from some considerations of the renormalization group and Coulomb gas model.The latter option is consistent with our MC data.Our MC results served as a basis for a critical reconsideration of some earlier theoretical conjectures and scaling assumptions.In particular,we have corrected and refined our previous analysis by grouping Feynman diagrams.The renewed analysis gives ω≈4-d-2η as some approximation for spatial dimensions d <4,or ω≈1.5 in two dimensions.展开更多
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer（CRC）.The long-term use of non-steroidal anti-inflammatory drugs（NSAIDs） has been shown to reduce the...The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer（CRC）.The long-term use of non-steroidal anti-inflammatory drugs（NSAIDs） has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies.The NSA1 D sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC.The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity.Emerging evidence suggests that sulindac inhibits the growth of colon tumor cells by suppressing the activity of certain phosphodiesterase isozymes to activate cGMβ-dependent protein kinase,PKG,through the elevation of the second messenger cyclic guanosine monophosphote,cGMP.PKG activation has been shown to inhibit the nuclear translocation of β-catenin,reduce β-catenin mRNA and protein levels,and suppress the transcriptional activity of β-catenin.This review describes the relationship between the Wnt/β-catenin signaling cascade and the activation of PKG through PDE inhibition and elevation of intracellular cGMP levels.展开更多
AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induce...AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.展开更多
AIM To evaluate whether non-steroidal anti-inflammatory drugs(NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity.METHODS Gastric ulcer pain was induced by the oral admin...AIM To evaluate whether non-steroidal anti-inflammatory drugs(NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity.METHODS Gastric ulcer pain was induced by the oral administration of indomethacin to male,CD1 mice(n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential(TRP),sodium and acid-sensing ion channels(ASICs) as well as opioid receptors and guanylate cyclase C(GC-C). RESULTS Results showed that two opioids and a GC-C agonist,morphine,asimadoline and linaclotide,respectively,the TRP antagonists,AMG9810 and HC-030031 and the sodium channel blocker,carbamazepine,elicited a dose-and/or time-dependent attenuation of referred visceral hypersensitivity,while the ASIC blocker,amiloride,was ineffective at all doses tested. CONCLUSION Together,these findings implicate opioid receptors,GC-C,and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly,these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.展开更多
The mechanism of a retracting cantilevered beam has been investigated by the invariant and energy-based analysis. The time-varying parameter partial differential equation governing the transverse vibrations of a beam ...The mechanism of a retracting cantilevered beam has been investigated by the invariant and energy-based analysis. The time-varying parameter partial differential equation governing the transverse vibrations of a beam with retracting motion is derived based on the momentum theorem. The assumed-mode method is used to truncate the governing partial differential equation into a set of ordinary differential equations (ODEs) with time-dependent coefficients. It is found that if the order of truncation is not less than the order of the initial conditions, the assumed-mode method can yield accurate results. The energy transfers among assumed modes are discussed during retraction. The total energy varying with time has been investigated by numerical and analytical methods, and the results have good agreement with each other. For the transverse vibrations of the axially retracting beam, the adiabatic invariant is derived by both the averaging method and the Bessel function method. (C) 2016 Chinese Society of Aeronautics and Astronautics. Production and hosting by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.展开更多
Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protec...Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.展开更多
Objective In this study,the combined effect of two stressors,namely,electromagnetic fields(EMFs)from mobile phones and fructose consumption,on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP...Objective In this study,the combined effect of two stressors,namely,electromagnetic fields(EMFs)from mobile phones and fructose consumption,on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance.Methods Weaned Wistar rats(28 days old)were divided into 4 groups:Normal,Exposure Only(ExpO),Fructose Only(FruO),and Exposure and Fructose(EF).Each group was provided standard laboratory chow ad libitum for 8 weeks.Additionally,the control groups,namely,the Normal and FruO groups,had unrestricted access to drinking water and fructose solution(15%),respectively.Furthermore,the respective treatment groups,namely,the ExpO and EF groups,received EMF exposure(1,760 MHz,2 h/day x 8 weeks).In early adulthood,mitochondrial function,insulin receptor signaling,and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis.Result In the hypothalamic tissue of EF,SIRT1,FOXO 1,p-PI3K,p-AKT,ComplexⅢ,UCP2,MnSOD,and catalase expressions and OXPHOS and GSH activities were significantly decreased(P<0.05)compared to the Normal,ExpO,and FruO groups.In hepatic tissue of EF,the p-AMPKα,SIRT1,FOXO1,IRS1,p-PI3K,ComplexⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,UCP2,and MnSOD expressions and the activity of OXPHOS,SOD,catalase,and GSH were significantly reduced compared to the Normal group(P<0.05).Conclusion The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals,mitochondrial OXPHOS,and the antioxidant defense system in the hypothalamus and liver.展开更多
Interleukin-35(IL-35)is a novel protein comprising IL-12αand IL-27βchains.The IL12A and EBI3 genes are responsible for its production.The study of IL-35 has experienced a substantial increase in interest in recent y...Interleukin-35(IL-35)is a novel protein comprising IL-12αand IL-27βchains.The IL12A and EBI3 genes are responsible for its production.The study of IL-35 has experienced a substantial increase in interest in recent years,as demonstrated by many research papers.Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum.This is accompanied by a drop in the percentage of IL-35+Treg cells,regulatory B cells,and CD8+FOXP3+cells that produce IL-35.This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation.It demonstrates IL-35's ability to regulate cytokine proportions,modulate B cells,and protect against autoimmune diabetes.However,further investigation is necessary to ascertain the precise mechanism of IL-35,and meticulous planning is essential for clinical studies.展开更多
This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide der...This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.展开更多
Purpose: To investigate the association between the maximum cystometric capacity (MCC) and other cystometric parameters in lumbar canal stenosis (LCS) rats. Material and Methods: One small hole was drilled at the fift...Purpose: To investigate the association between the maximum cystometric capacity (MCC) and other cystometric parameters in lumbar canal stenosis (LCS) rats. Material and Methods: One small hole was drilled at the fifth lumbar vertebral arch (Sham), and a rectangular piece of silicone rubber was then placed in the epidural space (LCS) of Wister rats. Two weeks after surgery, awake cystometry was performed. LCS rats were divided into three groups: Group A (n = 5, MCC < 0.87 mL), Group B (n = 13, MCC 0.87 - 1.81 mL), and Group C (n = 14, MCC > 1.81 mL). Cystometric parameters were investigated in sham and LCS groups. Results: MCC did not significantly correlate to the frequency of non-voiding contractions (NVCs), voided volume (VV), or maximum intravesical pressure during voiding (Pmax), but significantly positively correlated to postvoid residual urine volume (PVR) and residual urine rate (RUR) (Spearman’s correlation coefficients (ρ) = 0.8973 (p < 0.0001) and 0.4915 (p = 0.0068), respectively). Compared with the sham rats, LCS rats in each group revealed significantly smaller VV, larger RUR, and lower Pmax. On the other hand, among LCS rats, VV, RUR, and Pmax were not significantly different. The frequency of NVCs in each LCS group was not significantly different from that in sham-operated rats (Tukey-Kramer’s HSD test). However, a Jonckheere-Terpstra trend test revealed a significant trend toward higher NVCs in the order of sham, Groups C, B, and A (p = 0.036). Conclusions: LCS rats showed the same degree of detrusor underactivity regardless of MCC. NVCs did not significantly increase in LCS rats with decreased MCC, but the trend toward higher NVCs with smaller MCC was significant.展开更多
ATP-binding cassette（ABC） transporters ABCC1（MRP1）,ABCB1（P-gp）,and ABCG2（BCRP） contribute to chemotherapy failure.The primary goals of this study were to characterize the efficacy and mechanism of the nonstero...ATP-binding cassette（ABC） transporters ABCC1（MRP1）,ABCB1（P-gp）,and ABCG2（BCRP） contribute to chemotherapy failure.The primary goals of this study were to characterize the efficacy and mechanism of the nonsteroidal anti-inflammatory drug（NSAID）,sulindac sulfide,to reverse ABCC1 mediated resistance to chemotherapeutic drugs and to determine if sulindac sulfide can influence sensitivity to chemotherapeutic drugs independently of drug efflux.Cytotoxicity assays were performed to measure resistance of ABC-expressing cell lines to doxorubicin and other chemotherapeutic drugs.NSAIDs were tested for the ability to restore sensitivity to resistance selected tumor cell lines,as well as a large panel of standard tumor cell lines.Other experiments characterized the mechanism by which sulindac sulfide inhibits ABCC1 substrate and co-substrate（GSH） transport in isolated membrane vesicles and intact cells.Selective reversal of multi-drug resistance（MDR）,decreased efflux of doxorubicin,and fluorescent substrates were demonstrated by sulindac sulfide and a related NSAID,indomethacin,in resistance selected and engineered cell lines expressing ABCC 1,but not ABCB 1 or ABCG2.Sulindac sulfide also inhibited transport of leukotriene C_4 into membrane vesicles.Sulindac sulfide enhanced the sensitivity to doxorubicin in 24 of 47 tumor cell lines,including all melanoma lines tested（7-7）.Sulindac sulfide also decreased intracellular GSH in ABCC1 expressing cells,while the glutathione synthesis inhibitor,BSO,selectively increased sensitivity to sulindac sulfide induced cytotoxicity.Sulindac sulfide potently and selectively reverses ABCC1-mediated MDR at clinically achievable concentrations.ABCC1 expressing tumors may be highly sensitive to the direct cytotoxicity of sulindac sulfide,and in combination with chemotherapeutic drugs that induce oxidative stress.展开更多
Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly con...Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.展开更多
[ Objective ] This study aimed to investigate the optimal method for extracting RNA from roots of medicinal plant herba violae by comparing the effects of liquid nitrogen grinding method and low-temperature sectioning...[ Objective ] This study aimed to investigate the optimal method for extracting RNA from roots of medicinal plant herba violae by comparing the effects of liquid nitrogen grinding method and low-temperature sectioning method on RNA extraction. [ Method] Roots of herba violae were respectively crushed by using liquid nitrogen grinding method and low-temperature sectioning method to extract RNA. The extraction effects of these two methods were compared based on detec- tion of RNA concentration, purity and integrity and amplification of GAPDH gene by RT-PCR. [Result] The concentration of RNA extracted by liquid nitrogen grinding method and low-temperature sectioning method was 1.21 and 3.57 p^g/~, respectively. Both RNA extracted by these two methods showed two distinct bands after agarose gel electrophoresis. The ratio of brightness of the 28S rRNA to the 18S rRNA bands was greater than 1. PCR amplification showed that the length of GAPDH gene was about 230 bp, which was consistent with the expected result. [ Conclusion ] The experimental results indicated that using low-tempera ture sectioning method to crush the roots of herba violae can meet the needs of most molecular biological experiments including gene cloning and expression analysis, which is an effective and simple method for extracting RNA from plant roots.展开更多
An easy, safe, solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide （C...An easy, safe, solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide （C-200） in high yield within short span of time. All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide （C-200）. Results are also compared with sodium hydroxide and potassium hydroxide.展开更多
We established a QT interval assessment system that uses human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indic...We established a QT interval assessment system that uses human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. To investigate the applicability of the hES-CMC system to drug safety assessment, we investigated short-term variability in FPDc (STVFPDc) (beat rate rhythmicity) as a marker of torsadogenic risk. We investigated the FPDc and STVFPDc of hES-CMCs treated with hERG channel blockers (E-4031 or cisapride) or with our proprietary compounds X, Y, and Z. We also evaluated the electrocardiograms and hemodynamics of dogs treated with compound X, Y, or Z. The torsadogenic hERG channel blockers increased STVFPDc and prolonged FPDc. Compounds X, Y, and Z had hERG inhibitory activity. Compound X prolonged FPDc with increased STVFPDc, whereas compounds Y and Z tended to shorten FPDc in the hES-CMC system. In the in vivo canine study, compound X prolonged corrected QT (QTc), and compounds Y and Z tended to shorten QTc, showing a good correlation with the results in hES-CMCs. These findings suggest that combined assessment of FPDc and STVFPDc in the hES-CMC system increases the predictability of torsadogenic risk.展开更多
Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given tha...Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.展开更多
Engineered nanomaterials have attracted significantly attention as one of the most promising antimicrobial agents for against multidrug resistant infections.The toxicological responses of nano mate rials are closely r...Engineered nanomaterials have attracted significantly attention as one of the most promising antimicrobial agents for against multidrug resistant infections.The toxicological responses of nano mate rials are closely related to their physicochemical properties,and establishment of a structure-activity relationship for nanomaterials at the nano-bio interface is of great significance for deep understanding antibacterial toxicity mechanisms of nanomaterials and designing safer antibacterial nanomaterials.In this study,the antibacterial behaviors of well-defined crystallographic facets of a series of Au nanocrystals,including{100}-facet cubes,{110}-facet rhombic dodecahedra,{111}-facet octahedra,{221}-facet trisoctahedra and{720}-facet concave cubes,was investigated,using the model bacteria Staphylococcus aureus.We find that Au nanocrystals display substantial facet-dependent antibacterial activities.The low-index facets of cubes,octahedra,and rhombic dodecahedra show considerable antibacterial activity,whereas the high-index facets of trisoctahedra and concave cubes remained inert under biological conditions.This result is in stark contrast to the previous paradigm that the high-index facets were considered to have higher bioactivity as compared with low-index facets.The antibacterial mechanism studies have shown that the facet-dependent antibacterial behaviors of Au nanocrystals are mainly caused by differential bacterial membrane damage as well as inhibition of cellular enzymatic activity and energy metabolism.The faceted Au nanocrystals are unique in that they do not induce generation of reactive oxygen species,as validated for most antibiotics and antimicrobial nanostructures.Our findings may provide a deeper understanding of facet-dependent toxicological responses and suggest the complexities of the na no material-cell interactions,shedding some light on the development of high performance Au nanomaterials-based antibacterial therapeutics.展开更多
Given the important roles of miRNAs in post-transcriptional gene regulation, identification of differentially expressed miRNAs will facilitate the elucidation of molecular mechanisms underlying kernel development. In ...Given the important roles of miRNAs in post-transcriptional gene regulation, identification of differentially expressed miRNAs will facilitate the elucidation of molecular mechanisms underlying kernel development. In this study, we constructed a small RNA library to comprehensively represent the full complement of individual small RNAs and to characterize miRNA expression profiles in pooled ears of maize(Zea mays L.) at 10, 15,20, 22, 25 and 30 days after pollination(DAP). At least 21 miRNAs were differentially expressed. The differential expression of three of these miRNAs, i.e., miR528a, miR167a and miR160b, at each stage was verified by qRT-PCR. The results indicated that these miRNAs might be involved in kernel development. In addition, the predicted functions of target genes indicated that most of the target genes are involved in signal transduction and cell communication pathways, particularly the auxin signaling pathway. The expression of candidate germination-associated miRNAs was analyzed by hybridization to a maize genome microarray, and revealed differential expression of genes involved in plant hormone signaling pathways. This finding suggests that phytohormones play a critical role in the development of maize kernels. We found that in combination with other miRNAs, miR528a regulated a putative laccase, a Ring-H2 zinc finger protein and a MADS box-like protein, whereas miR167a and miR160b regulated multiple target genes,including ARF(auxin response factor), a member of the B3 transcription factor family. All three miRNAs are important for ear germination, development and physiology. The small RNA transcriptomes and mRNA obtained in this study will help us gain a betterunderstanding of the expression and function of small RNAs in the development of maize kernel.展开更多
The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive ...The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.展开更多
文摘Monte Carlo(MC) simulations have been performed to refine the estimation of the correction-toscaling exponent ω in the 2D φ^(4)model,which belongs to one of the most fundamental universality classes.If corrections have the form ∝ L^(-ω),then we find ω=1.546(30) andω=1.509(14) as the best estimates.These are obtained from the finite-size scaling of the susceptibility data in the range of linear lattice sizes L ∈[128,2048] at the critical value of the Binder cumulant and from the scaling of the corresponding pseudocritical couplings within L∈[64,2048].These values agree with several other MC estimates at the assumption of the power-law corrections and are comparable with the known results of the ε-expansion.In addition,we have tested the consistency with the scaling corrections of the form ∝ L^(-4/3),∝L^(-4/3)In L and ∝L^(-4/3)/ln L,which might be expected from some considerations of the renormalization group and Coulomb gas model.The latter option is consistent with our MC data.Our MC results served as a basis for a critical reconsideration of some earlier theoretical conjectures and scaling assumptions.In particular,we have corrected and refined our previous analysis by grouping Feynman diagrams.The renewed analysis gives ω≈4-d-2η as some approximation for spatial dimensions d <4,or ω≈1.5 in two dimensions.
文摘The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer（CRC）.The long-term use of non-steroidal anti-inflammatory drugs（NSAIDs） has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies.The NSA1 D sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC.The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity.Emerging evidence suggests that sulindac inhibits the growth of colon tumor cells by suppressing the activity of certain phosphodiesterase isozymes to activate cGMβ-dependent protein kinase,PKG,through the elevation of the second messenger cyclic guanosine monophosphote,cGMP.PKG activation has been shown to inhibit the nuclear translocation of β-catenin,reduce β-catenin mRNA and protein levels,and suppress the transcriptional activity of β-catenin.This review describes the relationship between the Wnt/β-catenin signaling cascade and the activation of PKG through PDE inhibition and elevation of intracellular cGMP levels.
文摘AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.
文摘AIM To evaluate whether non-steroidal anti-inflammatory drugs(NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity.METHODS Gastric ulcer pain was induced by the oral administration of indomethacin to male,CD1 mice(n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential(TRP),sodium and acid-sensing ion channels(ASICs) as well as opioid receptors and guanylate cyclase C(GC-C). RESULTS Results showed that two opioids and a GC-C agonist,morphine,asimadoline and linaclotide,respectively,the TRP antagonists,AMG9810 and HC-030031 and the sodium channel blocker,carbamazepine,elicited a dose-and/or time-dependent attenuation of referred visceral hypersensitivity,while the ASIC blocker,amiloride,was ineffective at all doses tested. CONCLUSION Together,these findings implicate opioid receptors,GC-C,and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly,these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.
基金supported by the National Natural Science Foundation of China (Nos. 11322214, 11172010, 11290152 and 11402007)supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canada Research Chair (CRC) Program+1 种基金the Bizkaia Talent Grant under the Basque Government through the BERC 2014–2017 ProgramSpanish Ministry of Economy and Competitiveness MINECO:BCAM Severo Ochoa excellence accreditation SEV-2013-0323
文摘The mechanism of a retracting cantilevered beam has been investigated by the invariant and energy-based analysis. The time-varying parameter partial differential equation governing the transverse vibrations of a beam with retracting motion is derived based on the momentum theorem. The assumed-mode method is used to truncate the governing partial differential equation into a set of ordinary differential equations (ODEs) with time-dependent coefficients. It is found that if the order of truncation is not less than the order of the initial conditions, the assumed-mode method can yield accurate results. The energy transfers among assumed modes are discussed during retraction. The total energy varying with time has been investigated by numerical and analytical methods, and the results have good agreement with each other. For the transverse vibrations of the axially retracting beam, the adiabatic invariant is derived by both the averaging method and the Bessel function method. (C) 2016 Chinese Society of Aeronautics and Astronautics. Production and hosting by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
基金financially supported by the Natural Science Foundation of Education Department of Sichuan Province of China,No.14ZB0152the Joint Research Program of Luzhou and Southwest Medical University,in China,No.14JC0120
文摘Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.
基金supported by the Indian Council of Medical Research(ICMR)in New Delhi.(Sanction NO:5/10/FR/13/2015-RBMH)。
文摘Objective In this study,the combined effect of two stressors,namely,electromagnetic fields(EMFs)from mobile phones and fructose consumption,on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance.Methods Weaned Wistar rats(28 days old)were divided into 4 groups:Normal,Exposure Only(ExpO),Fructose Only(FruO),and Exposure and Fructose(EF).Each group was provided standard laboratory chow ad libitum for 8 weeks.Additionally,the control groups,namely,the Normal and FruO groups,had unrestricted access to drinking water and fructose solution(15%),respectively.Furthermore,the respective treatment groups,namely,the ExpO and EF groups,received EMF exposure(1,760 MHz,2 h/day x 8 weeks).In early adulthood,mitochondrial function,insulin receptor signaling,and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis.Result In the hypothalamic tissue of EF,SIRT1,FOXO 1,p-PI3K,p-AKT,ComplexⅢ,UCP2,MnSOD,and catalase expressions and OXPHOS and GSH activities were significantly decreased(P<0.05)compared to the Normal,ExpO,and FruO groups.In hepatic tissue of EF,the p-AMPKα,SIRT1,FOXO1,IRS1,p-PI3K,ComplexⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,UCP2,and MnSOD expressions and the activity of OXPHOS,SOD,catalase,and GSH were significantly reduced compared to the Normal group(P<0.05).Conclusion The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals,mitochondrial OXPHOS,and the antioxidant defense system in the hypothalamus and liver.
文摘Interleukin-35(IL-35)is a novel protein comprising IL-12αand IL-27βchains.The IL12A and EBI3 genes are responsible for its production.The study of IL-35 has experienced a substantial increase in interest in recent years,as demonstrated by many research papers.Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum.This is accompanied by a drop in the percentage of IL-35+Treg cells,regulatory B cells,and CD8+FOXP3+cells that produce IL-35.This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation.It demonstrates IL-35's ability to regulate cytokine proportions,modulate B cells,and protect against autoimmune diabetes.However,further investigation is necessary to ascertain the precise mechanism of IL-35,and meticulous planning is essential for clinical studies.
基金National Institute of Technology Karnataka,India for the financial support and laboratory facility
文摘This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.
文摘Purpose: To investigate the association between the maximum cystometric capacity (MCC) and other cystometric parameters in lumbar canal stenosis (LCS) rats. Material and Methods: One small hole was drilled at the fifth lumbar vertebral arch (Sham), and a rectangular piece of silicone rubber was then placed in the epidural space (LCS) of Wister rats. Two weeks after surgery, awake cystometry was performed. LCS rats were divided into three groups: Group A (n = 5, MCC < 0.87 mL), Group B (n = 13, MCC 0.87 - 1.81 mL), and Group C (n = 14, MCC > 1.81 mL). Cystometric parameters were investigated in sham and LCS groups. Results: MCC did not significantly correlate to the frequency of non-voiding contractions (NVCs), voided volume (VV), or maximum intravesical pressure during voiding (Pmax), but significantly positively correlated to postvoid residual urine volume (PVR) and residual urine rate (RUR) (Spearman’s correlation coefficients (ρ) = 0.8973 (p < 0.0001) and 0.4915 (p = 0.0068), respectively). Compared with the sham rats, LCS rats in each group revealed significantly smaller VV, larger RUR, and lower Pmax. On the other hand, among LCS rats, VV, RUR, and Pmax were not significantly different. The frequency of NVCs in each LCS group was not significantly different from that in sham-operated rats (Tukey-Kramer’s HSD test). However, a Jonckheere-Terpstra trend test revealed a significant trend toward higher NVCs in the order of sham, Groups C, B, and A (p = 0.036). Conclusions: LCS rats showed the same degree of detrusor underactivity regardless of MCC. NVCs did not significantly increase in LCS rats with decreased MCC, but the trend toward higher NVCs with smaller MCC was significant.
文摘ATP-binding cassette（ABC） transporters ABCC1（MRP1）,ABCB1（P-gp）,and ABCG2（BCRP） contribute to chemotherapy failure.The primary goals of this study were to characterize the efficacy and mechanism of the nonsteroidal anti-inflammatory drug（NSAID）,sulindac sulfide,to reverse ABCC1 mediated resistance to chemotherapeutic drugs and to determine if sulindac sulfide can influence sensitivity to chemotherapeutic drugs independently of drug efflux.Cytotoxicity assays were performed to measure resistance of ABC-expressing cell lines to doxorubicin and other chemotherapeutic drugs.NSAIDs were tested for the ability to restore sensitivity to resistance selected tumor cell lines,as well as a large panel of standard tumor cell lines.Other experiments characterized the mechanism by which sulindac sulfide inhibits ABCC1 substrate and co-substrate（GSH） transport in isolated membrane vesicles and intact cells.Selective reversal of multi-drug resistance（MDR）,decreased efflux of doxorubicin,and fluorescent substrates were demonstrated by sulindac sulfide and a related NSAID,indomethacin,in resistance selected and engineered cell lines expressing ABCC 1,but not ABCB 1 or ABCG2.Sulindac sulfide also inhibited transport of leukotriene C_4 into membrane vesicles.Sulindac sulfide enhanced the sensitivity to doxorubicin in 24 of 47 tumor cell lines,including all melanoma lines tested（7-7）.Sulindac sulfide also decreased intracellular GSH in ABCC1 expressing cells,while the glutathione synthesis inhibitor,BSO,selectively increased sensitivity to sulindac sulfide induced cytotoxicity.Sulindac sulfide potently and selectively reverses ABCC1-mediated MDR at clinically achievable concentrations.ABCC1 expressing tumors may be highly sensitive to the direct cytotoxicity of sulindac sulfide,and in combination with chemotherapeutic drugs that induce oxidative stress.
文摘Alzheimer’s disease (AD) is caused by synaptic failure and the excessive accumulation of misfolded proteins especially Aβ and tau, and associated with memory loss and cognitive impairment. Treatment of AD mainly consists of symptomatic therapy and disease-modifying therapy (DMT). Several monotherapies including small molecules or antibodies have been evaluated through multiple clinical trials, but a very few have been approved by the USFDA to intervene the disease’s pathogenesis. Past research has shown multifactorial nature of AD, therefore, multi-target drugs were proposed to target different pathways at the same time, however, currently no rationally designed multi-target directed ligand (MTDL) has been clinically approved. Different combinations and bispecific antibodies are also under development. Novel approaches like stem cell-based therapies, microRNAs, peptides, ADCs and vaccines cast a new hope for AD treatment, however, a number of questions remained to be answered prior to their safe and effective clinical translation. This review explores the small molecules, MTDL, and antibodies (monospecific and bispecific) for the treatment of AD. Finally, future perspectives (stem cell therapy, PROTAC approaches, microRNAs, ADC, peptides and vaccines) are also discussed with regard to their clinical applications and feasibility.
基金Supported by National Natural Science Foundation of China(81001700)Project of Sichuan Provincial Education Department(11ZB227,11ZB124)Research Project for the Application Foundation of Sichuan Provincial Science and Technology Department(2012JY0081)
文摘[ Objective ] This study aimed to investigate the optimal method for extracting RNA from roots of medicinal plant herba violae by comparing the effects of liquid nitrogen grinding method and low-temperature sectioning method on RNA extraction. [ Method] Roots of herba violae were respectively crushed by using liquid nitrogen grinding method and low-temperature sectioning method to extract RNA. The extraction effects of these two methods were compared based on detec- tion of RNA concentration, purity and integrity and amplification of GAPDH gene by RT-PCR. [Result] The concentration of RNA extracted by liquid nitrogen grinding method and low-temperature sectioning method was 1.21 and 3.57 p^g/~, respectively. Both RNA extracted by these two methods showed two distinct bands after agarose gel electrophoresis. The ratio of brightness of the 28S rRNA to the 18S rRNA bands was greater than 1. PCR amplification showed that the length of GAPDH gene was about 230 bp, which was consistent with the expected result. [ Conclusion ] The experimental results indicated that using low-tempera ture sectioning method to crush the roots of herba violae can meet the needs of most molecular biological experiments including gene cloning and expression analysis, which is an effective and simple method for extracting RNA from plant roots.
文摘An easy, safe, solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide （C-200） in high yield within short span of time. All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide （C-200）. Results are also compared with sodium hydroxide and potassium hydroxide.
文摘We established a QT interval assessment system that uses human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. To investigate the applicability of the hES-CMC system to drug safety assessment, we investigated short-term variability in FPDc (STVFPDc) (beat rate rhythmicity) as a marker of torsadogenic risk. We investigated the FPDc and STVFPDc of hES-CMCs treated with hERG channel blockers (E-4031 or cisapride) or with our proprietary compounds X, Y, and Z. We also evaluated the electrocardiograms and hemodynamics of dogs treated with compound X, Y, or Z. The torsadogenic hERG channel blockers increased STVFPDc and prolonged FPDc. Compounds X, Y, and Z had hERG inhibitory activity. Compound X prolonged FPDc with increased STVFPDc, whereas compounds Y and Z tended to shorten FPDc in the hES-CMC system. In the in vivo canine study, compound X prolonged corrected QT (QTc), and compounds Y and Z tended to shorten QTc, showing a good correlation with the results in hES-CMCs. These findings suggest that combined assessment of FPDc and STVFPDc in the hES-CMC system increases the predictability of torsadogenic risk.
文摘Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.
基金the National Key Research and Development Program of China(No.2017YFA0205300)the National Natural Science Foundation of China(Nos.21675023 and 91753106)the Scientific Research Foundation of Southwest Medical University(No.19120200037)。
文摘Engineered nanomaterials have attracted significantly attention as one of the most promising antimicrobial agents for against multidrug resistant infections.The toxicological responses of nano mate rials are closely related to their physicochemical properties,and establishment of a structure-activity relationship for nanomaterials at the nano-bio interface is of great significance for deep understanding antibacterial toxicity mechanisms of nanomaterials and designing safer antibacterial nanomaterials.In this study,the antibacterial behaviors of well-defined crystallographic facets of a series of Au nanocrystals,including{100}-facet cubes,{110}-facet rhombic dodecahedra,{111}-facet octahedra,{221}-facet trisoctahedra and{720}-facet concave cubes,was investigated,using the model bacteria Staphylococcus aureus.We find that Au nanocrystals display substantial facet-dependent antibacterial activities.The low-index facets of cubes,octahedra,and rhombic dodecahedra show considerable antibacterial activity,whereas the high-index facets of trisoctahedra and concave cubes remained inert under biological conditions.This result is in stark contrast to the previous paradigm that the high-index facets were considered to have higher bioactivity as compared with low-index facets.The antibacterial mechanism studies have shown that the facet-dependent antibacterial behaviors of Au nanocrystals are mainly caused by differential bacterial membrane damage as well as inhibition of cellular enzymatic activity and energy metabolism.The faceted Au nanocrystals are unique in that they do not induce generation of reactive oxygen species,as validated for most antibiotics and antimicrobial nanostructures.Our findings may provide a deeper understanding of facet-dependent toxicological responses and suggest the complexities of the na no material-cell interactions,shedding some light on the development of high performance Au nanomaterials-based antibacterial therapeutics.
基金supported by grants from the Educational Commission of Sichuan Province (No. 2006J13-039)the Doctoral Program Foundation of Institutions of Higher Education of China (No. 20095103120002)the National Natural Science Foundation of China (No. 30900901)
文摘Given the important roles of miRNAs in post-transcriptional gene regulation, identification of differentially expressed miRNAs will facilitate the elucidation of molecular mechanisms underlying kernel development. In this study, we constructed a small RNA library to comprehensively represent the full complement of individual small RNAs and to characterize miRNA expression profiles in pooled ears of maize(Zea mays L.) at 10, 15,20, 22, 25 and 30 days after pollination(DAP). At least 21 miRNAs were differentially expressed. The differential expression of three of these miRNAs, i.e., miR528a, miR167a and miR160b, at each stage was verified by qRT-PCR. The results indicated that these miRNAs might be involved in kernel development. In addition, the predicted functions of target genes indicated that most of the target genes are involved in signal transduction and cell communication pathways, particularly the auxin signaling pathway. The expression of candidate germination-associated miRNAs was analyzed by hybridization to a maize genome microarray, and revealed differential expression of genes involved in plant hormone signaling pathways. This finding suggests that phytohormones play a critical role in the development of maize kernels. We found that in combination with other miRNAs, miR528a regulated a putative laccase, a Ring-H2 zinc finger protein and a MADS box-like protein, whereas miR167a and miR160b regulated multiple target genes,including ARF(auxin response factor), a member of the B3 transcription factor family. All three miRNAs are important for ear germination, development and physiology. The small RNA transcriptomes and mRNA obtained in this study will help us gain a betterunderstanding of the expression and function of small RNAs in the development of maize kernel.
文摘The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.
