Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures o...Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures of cardiac myocytes from 1-to 3-day-old Wistar rats were prepared,and myocytes were ex-posed to lipopolysaccharide(LPS)and varying concentrations of PPARαor PPARγactivator(fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα,PPARα,and PPARγexpression in cultured cardiac myocytes.Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB(NF-κB)binding site to cardiac myocytes was performed.Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner.However,no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone.Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter(-721/+17)after being stimulated with LPS and fenofibrate or pioglitazone,whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site(-182/+17).Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression.Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation.The mechanism may partly be involved in suppression of the NF-κB pathway.展开更多
Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its com...Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.展开更多
A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-...A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.展开更多
The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a ...The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.展开更多
Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the pos...Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.展开更多
The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were d...The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.展开更多
Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding whee...Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding wheels were then prepared from Ni-coated diamond composite powders with different activators. The microstructural characterizations of this composite powders were finally conducted by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction, and the mechanical and tribological properties of as-prepared diamond grinding wheels were also measured. There are changes in microstructures and properties of the composite powders with activators. The activator concentration also has an influence on the morphologies and phase structures of the Ni coating on diamond particles.The composite powders with more compact coating of nickel can be prepared by adding 1 g dm^（-3） or more AgNO_3 as an activator to electrodeposit nickel on diamond. The mechanical and tribological properties of diamond grinding wheels were significantly improved when the coating phase structure of Ni crystal grew with（111） plane orientation on the surface of diamond particles. The wheels made from nickel coated diamond composite powders possessed the advantages of easy preparation and outstanding tribological properties. Therefore, Ni coated diamond composite powders exhibit a great potential to be extensively applied in diamond cutting and grinding tools.展开更多
Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial...Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial cells (EC-CM),the PA activities of the latter decreased significantly. Cocultivation of EC with SMC alsoresulted in a significant decrease (70.7%) of PA activities produced by EC. Sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of SMC-CMfollowed by reverse fibrin autography demonstrated that the PA inhibitor had a molecularweight of 49000-62000. In this study we also investigated the effect of a Chinese herbalmedicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity of SMC. The re-sults showed that RSM significantly decreased the inhibitory activity of SMC against thePA secreted by EC.展开更多
Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators agains...Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators against Src homology region 2 domain-containing phosphatase-1(SHP-1)to block STAT3 pathway represents a promising strategy for DLBCL therapy.Here we reported a new class of thieno[2,3-b]quinolineprocaine hybrid molecules as SHP-1 allosteric activators.The representative hybrid compound 3b displayed SHP-1 activating effect with EC50 of 5.48±0.28μmol/L.Further investigations confirmed that 3b allosterically interacted with SHP-1,switched it from close to open conformation,blocked SHP-1/p-STAT3 pathway,induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro,and delayed tumor growth in the xenograft model of SU-DHL-2.Overall,this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors,and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway.展开更多
Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted...Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted and a series of benzotriazole derivatives were designed and synthesized.The bioassay showed that benzotriazole had high activity against a broad spectrum of diseases including fungi and oomycetes in vivo,but no activity in vitro.And the introduction of proper groups at the1＇-position and 5＇-position was beneficial to the activity.So,they had the potential to be exploited as novel plant activators.展开更多
The demand for multidimensional stimulus sensing devices that can be used for the real-time monitoring of the equipment status in complex working environments has led to investigations on multifunctional optoelectroni...The demand for multidimensional stimulus sensing devices that can be used for the real-time monitoring of the equipment status in complex working environments has led to investigations on multifunctional optoelectronic materials.Nevertheless,the exploitation of all-in-one materials with multimode and multicolor luminescence capacities is still immature.Given the abundant transitions in lanthanide ions and the stress-responsive ability of piezoelectric crystals,multi-activator-doped piezoelectric materials are promising candidates for multifunctional detection based on luminescence characteristics.Herein,we report a novel multidimensional stimulus-sensitive material constructed via combining dual luminescence centers(Bi^(3+)/Er^(3+))with piezoelectric LiTaO_(3),thus realizing opto-mechano-thermo-responsive luminescence in a single material.Particularly the photoluminescence is allochroic(cyangreen-yellow)under diverse excitation sources(ultraviolet-blue-near infrared radiation).Its mechanoluminescence performance shows a linear relation with the applied load,allowing its application in stress sensing.In addition,the thermally coupled levels of Er^(3+)dopants endow the LiTaO_(3)material with temperature sensing capacity relying on the fluorescence intensity ratio.These findings provide a new method for designing optical function materials and integrated optoelectronic devices toward radiative,stress,and temperature sensing applications.展开更多
Type 2 diabetes mellitus(T2DM)is a complex metabolic disorder characterized by multifactorial pathogenesis,in which therapies targeting a single mechanism often fail to achieve optimal glycemic control.In recent years...Type 2 diabetes mellitus(T2DM)is a complex metabolic disorder characterized by multifactorial pathogenesis,in which therapies targeting a single mechanism often fail to achieve optimal glycemic control.In recent years,glucokinase(GK),a key regulatory enzyme in glucose homeostasis,has emerged as a promising anti-diabetic target,attracting considerable attention from researchers.Acting as a glucose sensor,GK initiates counter-regulatory responses in response to fluctuations in blood glucose,thereby contributing to the restoration and maintenance of normoglycemia.Activation of GK enhances glucose metabolism and lowers blood glucose levels,representing a potential therapeutic strategy for the management of type 2 diabetes.GK activators(GKAs),a novel class of anti-diabetic agents,have therefore garnered significant interest.This article provides a comprehensive review of the functional role of GK in diabetes,elucidates the mechanistic action of GKAs at the protein level,and summarizes current research progress,emerging trends,and prospects regarding the clinical application of GKAs.展开更多
Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistan...Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.展开更多
The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat ...The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat proteins(NLRs)represent the largest family of intracellular immune receptors,responsible for the detection of rapidly evolving pathogen-secreted effec-tors and the initiation of effector-triggered immunity(ETI).展开更多
Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible p...Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter.Previous reconstruction of gene circuits highly improved transcriptional activity,but excessive expression of chimeric transactivator damaged cell growth on methanol.Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regula-tory networks.The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism,especially the alcohol oxidase 1(AOX1),but without remarkable changes in expression of transcriptional factors.Meanwhile,the synthesis of peroxisomes also varied with chimeric transactivator expression.In addition,the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism.The gene expression patterns caused by different expression levels of chimeric trans-activators have also been clarified.This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling.It revealed the importance of balancing transcription factor expression for the host improvement.展开更多
Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observe...Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Lithium–sulfur(Li–S)batteries are promisingcandidates for next-generation energy storagegiven their high energy density and potential low cost.Chemically activated carbon(CAC)is often used fortheir cathodes,because ...Lithium–sulfur(Li–S)batteries are promisingcandidates for next-generation energy storagegiven their high energy density and potential low cost.Chemically activated carbon(CAC)is often used fortheir cathodes,because it has a high specific surfacearea for sulfur loading.We have developed a pressurizedphysical activation(PPA)method that producedan activated carbon(PPAC)with a high specific surfacearea comparable to that of CAC.The pore structure of PPAC could be changed and its use as a cathode material for Li–Sbatteries was investigated.Battery tests at different capacity rates(C-rates)showed that it had a much improved high-rate performancewith a discharge capacity of 900 mAh/(g of sulfur)at 1 C,in contrast to only 600 mAh/(g of sulfur)for CAC.Porestructure analyses showed that PPAC prepared at a high activation temperature(1000℃)had unusual channel-like mesoporesbetween the microdomains that are the basic structural units of artificial carbon materials.These are connected to microporesdeveloped in each microdomain,and deliver ions from the surroundings to the internal pores and vice versa.The well-developedmicropores and mesopores of PPAC respectively ensured the high adsorption of lithium polysulfides and a high rate ofion diffusion.Compared to CAC,PPAC is a high-performance,low-cost cathode material that is promising for use in futureLi–S batteries.展开更多
new heterocyclic dipeptide with a highly functionalized 1,2-oxazadecaline core,named trichodermamide H(1),and three known analogues,along with three known polyketides,were isolated from the fermentation extract of the...new heterocyclic dipeptide with a highly functionalized 1,2-oxazadecaline core,named trichodermamide H(1),and three known analogues,along with three known polyketides,were isolated from the fermentation extract of the mangrovederived fungus Penicillium janthinellum XLN32122.The structure of 1 was elucidated on the basis of extensive 1D and 2D NMR spectra data analysis,HR-ESI-MS,electronic circular dichroism(ECD)calculations.Trichodermamide B(3)exhibited better inhibitory effect on nitric oxide(NO)production in lipopolysaccharide(LPS)induced RAW 264.7 cells with an IC_(50)value of(13.13±0.005)μmol/L than that of the positive control dexamethasone[IC_(50)=(136.84±1.33)μmol/L].Compound 3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus(MRSA)with an IC_(50)value of 12.5μg/mL,while the positive control vancomycin showed an IC_(50)value of 1.563μg/mL.展开更多
Neutron Activation Dose Assessment Based on a Human Head Phantom Post-BNCT Guanchao Wu1,2, Zuokang Lin2, Zijian Zhang1,2, Zhiyuan Lin1,2, Yinan Zhu2, Ye Dai2 and Zhimin Dai2(1.ShanghaiTech University, Shanghai, 201210...Neutron Activation Dose Assessment Based on a Human Head Phantom Post-BNCT Guanchao Wu1,2, Zuokang Lin2, Zijian Zhang1,2, Zhiyuan Lin1,2, Yinan Zhu2, Ye Dai2 and Zhimin Dai2(1.ShanghaiTech University, Shanghai, 201210, China;2.Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China)展开更多
基金Supported by the National Nature Science Foundation of China(30270551)Military"10.5"Foundation(02M012).
文摘Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures of cardiac myocytes from 1-to 3-day-old Wistar rats were prepared,and myocytes were ex-posed to lipopolysaccharide(LPS)and varying concentrations of PPARαor PPARγactivator(fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα,PPARα,and PPARγexpression in cultured cardiac myocytes.Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB(NF-κB)binding site to cardiac myocytes was performed.Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner.However,no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone.Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter(-721/+17)after being stimulated with LPS and fenofibrate or pioglitazone,whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site(-182/+17).Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression.Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation.The mechanism may partly be involved in suppression of the NF-κB pathway.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073814,81973291,82122066,and 82003909)the Rising-Star Program of Shanghai Science and Technology Committee(Grant No.:19QA1411500).
文摘Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
基金financially supported by the National Nature Science Foundation of China(No.30572256)
文摘A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars(No.30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers Pr
文摘The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.
文摘Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.
基金financially supported by the National Basic Research Program of China (973 Program, No. 2010CB126100)the National High Technology Research and Development Program of China (863 Program, No. 2011AA10A207)+1 种基金the China 111 Project (No. B07023)the Fundamental Research Funds for the Central Universities.
文摘The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.
基金funded by the National Natural Science Foundation of China (Nos. 21476066 and 51271074)
文摘Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding wheels were then prepared from Ni-coated diamond composite powders with different activators. The microstructural characterizations of this composite powders were finally conducted by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction, and the mechanical and tribological properties of as-prepared diamond grinding wheels were also measured. There are changes in microstructures and properties of the composite powders with activators. The activator concentration also has an influence on the morphologies and phase structures of the Ni coating on diamond particles.The composite powders with more compact coating of nickel can be prepared by adding 1 g dm^（-3） or more AgNO_3 as an activator to electrodeposit nickel on diamond. The mechanical and tribological properties of diamond grinding wheels were significantly improved when the coating phase structure of Ni crystal grew with（111） plane orientation on the surface of diamond particles. The wheels made from nickel coated diamond composite powders possessed the advantages of easy preparation and outstanding tribological properties. Therefore, Ni coated diamond composite powders exhibit a great potential to be extensively applied in diamond cutting and grinding tools.
文摘Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial cells (EC-CM),the PA activities of the latter decreased significantly. Cocultivation of EC with SMC alsoresulted in a significant decrease (70.7%) of PA activities produced by EC. Sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of SMC-CMfollowed by reverse fibrin autography demonstrated that the PA inhibitor had a molecularweight of 49000-62000. In this study we also investigated the effect of a Chinese herbalmedicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity of SMC. The re-sults showed that RSM significantly decreased the inhibitory activity of SMC against thePA secreted by EC.
基金supported by National Natural Science Foundation of China(Nos.81773779,21772068 and 22277043)National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(No.2018ZX09711002-007-1)+1 种基金Natural Science Foundation of Jiangsu Province(No.BK20190608)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX22_2330).
文摘Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators against Src homology region 2 domain-containing phosphatase-1(SHP-1)to block STAT3 pathway represents a promising strategy for DLBCL therapy.Here we reported a new class of thieno[2,3-b]quinolineprocaine hybrid molecules as SHP-1 allosteric activators.The representative hybrid compound 3b displayed SHP-1 activating effect with EC50 of 5.48±0.28μmol/L.Further investigations confirmed that 3b allosterically interacted with SHP-1,switched it from close to open conformation,blocked SHP-1/p-STAT3 pathway,induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro,and delayed tumor growth in the xenograft model of SU-DHL-2.Overall,this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors,and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway.
基金financially supported by the National Basic Research Program of China(973 Program,No.2010CB126100)the National High Technology Research and Development Program of China(863 Program,No.2011AA10A207)+1 种基金the Shanghai Leading Academic Discipline Project(B507)the Fundamental Research Funds for the Central Universities
文摘Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted and a series of benzotriazole derivatives were designed and synthesized.The bioassay showed that benzotriazole had high activity against a broad spectrum of diseases including fungi and oomycetes in vivo,but no activity in vitro.And the introduction of proper groups at the1＇-position and 5＇-position was beneficial to the activity.So,they had the potential to be exploited as novel plant activators.
基金supported by the National Natural Science Foundation of China(Grant No.51572195)the Shanghai Sailing Program(20YF1456300).
文摘The demand for multidimensional stimulus sensing devices that can be used for the real-time monitoring of the equipment status in complex working environments has led to investigations on multifunctional optoelectronic materials.Nevertheless,the exploitation of all-in-one materials with multimode and multicolor luminescence capacities is still immature.Given the abundant transitions in lanthanide ions and the stress-responsive ability of piezoelectric crystals,multi-activator-doped piezoelectric materials are promising candidates for multifunctional detection based on luminescence characteristics.Herein,we report a novel multidimensional stimulus-sensitive material constructed via combining dual luminescence centers(Bi^(3+)/Er^(3+))with piezoelectric LiTaO_(3),thus realizing opto-mechano-thermo-responsive luminescence in a single material.Particularly the photoluminescence is allochroic(cyangreen-yellow)under diverse excitation sources(ultraviolet-blue-near infrared radiation).Its mechanoluminescence performance shows a linear relation with the applied load,allowing its application in stress sensing.In addition,the thermally coupled levels of Er^(3+)dopants endow the LiTaO_(3)material with temperature sensing capacity relying on the fluorescence intensity ratio.These findings provide a new method for designing optical function materials and integrated optoelectronic devices toward radiative,stress,and temperature sensing applications.
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disorder characterized by multifactorial pathogenesis,in which therapies targeting a single mechanism often fail to achieve optimal glycemic control.In recent years,glucokinase(GK),a key regulatory enzyme in glucose homeostasis,has emerged as a promising anti-diabetic target,attracting considerable attention from researchers.Acting as a glucose sensor,GK initiates counter-regulatory responses in response to fluctuations in blood glucose,thereby contributing to the restoration and maintenance of normoglycemia.Activation of GK enhances glucose metabolism and lowers blood glucose levels,representing a potential therapeutic strategy for the management of type 2 diabetes.GK activators(GKAs),a novel class of anti-diabetic agents,have therefore garnered significant interest.This article provides a comprehensive review of the functional role of GK in diabetes,elucidates the mechanistic action of GKAs at the protein level,and summarizes current research progress,emerging trends,and prospects regarding the clinical application of GKAs.
基金supported by Department of Science and Technology and Biotechnology,GoWB,India(Sanction No.:140(Sanc.)-BT/P/Budget/RD-75/2017 dated 16.11.2018)to U.CDST-FIST,GoI for providing infrastructure support to Department of Zoology,University of Calcutta+2 种基金CSIR,GoI,for funding their fellowship(File No.09/028(1066)/2018-EMRI and 09/028(1138)/2019-EMR-I,respectively)supported by a grant from the Natural Sciences and Engineering Research Council of Canadasupported by a Queen Elizabeth Ⅱ Diamond Jubilee Scholarship and an FRQ-NT scholarship.
文摘Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.
基金supported by the Outstanding Young Teacher of the“QingLan Project”of Jiangsu Province.
文摘The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat proteins(NLRs)represent the largest family of intracellular immune receptors,responsible for the detection of rapidly evolving pathogen-secreted effec-tors and the initiation of effector-triggered immunity(ETI).
基金supported by National Key Research and Development Program of China(2022YFC2805102)Young Scientist Fund of National Natural Science Foundation of China(32201206)China Postdoctoral Science Foundation(2022M711146)。
文摘Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter.Previous reconstruction of gene circuits highly improved transcriptional activity,but excessive expression of chimeric transactivator damaged cell growth on methanol.Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regula-tory networks.The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism,especially the alcohol oxidase 1(AOX1),but without remarkable changes in expression of transcriptional factors.Meanwhile,the synthesis of peroxisomes also varied with chimeric transactivator expression.In addition,the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism.The gene expression patterns caused by different expression levels of chimeric trans-activators have also been clarified.This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling.It revealed the importance of balancing transcription factor expression for the host improvement.
基金funding provided by Royal Institute of Technology.This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation(72110).
文摘Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
文摘Lithium–sulfur(Li–S)batteries are promisingcandidates for next-generation energy storagegiven their high energy density and potential low cost.Chemically activated carbon(CAC)is often used fortheir cathodes,because it has a high specific surfacearea for sulfur loading.We have developed a pressurizedphysical activation(PPA)method that producedan activated carbon(PPAC)with a high specific surfacearea comparable to that of CAC.The pore structure of PPAC could be changed and its use as a cathode material for Li–Sbatteries was investigated.Battery tests at different capacity rates(C-rates)showed that it had a much improved high-rate performancewith a discharge capacity of 900 mAh/(g of sulfur)at 1 C,in contrast to only 600 mAh/(g of sulfur)for CAC.Porestructure analyses showed that PPAC prepared at a high activation temperature(1000℃)had unusual channel-like mesoporesbetween the microdomains that are the basic structural units of artificial carbon materials.These are connected to microporesdeveloped in each microdomain,and deliver ions from the surroundings to the internal pores and vice versa.The well-developedmicropores and mesopores of PPAC respectively ensured the high adsorption of lithium polysulfides and a high rate ofion diffusion.Compared to CAC,PPAC is a high-performance,low-cost cathode material that is promising for use in futureLi–S batteries.
基金Project supported by the National Natural Science Foundation of China(No.32160108)the Science and Technology Special Fund of Hainan Province(No.ZDYF2024SHFZ116)+2 种基金the Specific Research Fund of the Innovation Center for Academicians of Hainan Province(No.YSPTZX202309)the Scientific Research Project of Hainan Higher Education Institutions(No.Hnky2022ZD-6)the Hainan Normal University National College Student Innovation Training Program(No.202411658006)。
文摘new heterocyclic dipeptide with a highly functionalized 1,2-oxazadecaline core,named trichodermamide H(1),and three known analogues,along with three known polyketides,were isolated from the fermentation extract of the mangrovederived fungus Penicillium janthinellum XLN32122.The structure of 1 was elucidated on the basis of extensive 1D and 2D NMR spectra data analysis,HR-ESI-MS,electronic circular dichroism(ECD)calculations.Trichodermamide B(3)exhibited better inhibitory effect on nitric oxide(NO)production in lipopolysaccharide(LPS)induced RAW 264.7 cells with an IC_(50)value of(13.13±0.005)μmol/L than that of the positive control dexamethasone[IC_(50)=(136.84±1.33)μmol/L].Compound 3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus(MRSA)with an IC_(50)value of 12.5μg/mL,while the positive control vancomycin showed an IC_(50)value of 1.563μg/mL.
文摘Neutron Activation Dose Assessment Based on a Human Head Phantom Post-BNCT Guanchao Wu1,2, Zuokang Lin2, Zijian Zhang1,2, Zhiyuan Lin1,2, Yinan Zhu2, Ye Dai2 and Zhimin Dai2(1.ShanghaiTech University, Shanghai, 201210, China;2.Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China)
