By the random distribution of metals in a single phase,entropy engineering is applied to construct dense neighboring active centers with diverse electronic and geometric structures,realizing the continuous optimizatio...By the random distribution of metals in a single phase,entropy engineering is applied to construct dense neighboring active centers with diverse electronic and geometric structures,realizing the continuous optimization of multiple primary reactions for oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Many catalysts developed through entropy engineering have been built in nearly equimolar ratios to pursue high entropy,hindering the identification of the active sites and potentially diluting the concentration of real active sites while weakening their electronic interactions with reaction intermediates.Herein,this work proposes an entropy-engineering strategy in metal nanoparticle-embedded nitrogen carbon electrocatalysts,implemented by entropy-engineered Prussian blue analogs(PBA)as precursors to enhance the catalytic activity of primary Cu-Fe active sites.Through the introduction of the micro-strains driven by entropy engineering,density functional theory(DFT)calculations and geometric phase analysis(GPA)using Lorentz electron microscopy further elucidate the optimization of the adsorption/desorption of intermediates.Furthermore,the multi-dimensional morphology and the size diminishment of the nanocrystals serve to expand the electrochemical area,maximizing the catalytic activity for both ORR and OER.Notably,the Zn-air battery assembled with CuFeCoNiZn-NC operated for over 1300 h with negligible decay.This work presents a paradigm for the design of low-cost electrocatalysts with entropy engineering for multi-step reactions.展开更多
The photophysical properties of fluorescent nucleobase analogs play a crucial role in nucleic acids detection and the investigation of their structural and functional characteristics.In this study,we computationally d...The photophysical properties of fluorescent nucleobase analogs play a crucial role in nucleic acids detection and the investigation of their structural and functional characteristics.In this study,we computationally designed a series of quasiintrinsic fluorescent probes according to natural guanine(G)for selectively identifying covalent N^(4)-acetylcytosine(4acC),a base that is highly correlated with active transcription and gene expression.This work aims to gain insight into the role of 4acC in biological regulation with minimal perturbation to the native DNA structure.The results indicate that these Ganalogs possess extended π-conjugation in comparison with the natural guanine,which could yield efficient fluorescence emission and red-shifted absorption.Especially,the 8-thienyl-2’-deoxyguanosine(ThG)exhibits the highest fluorescence intensity and avoids self-absorption on account of the large Stokes shifts(>67 nm).What is more,the fluorescence of ThG is unaffected to base pairing with natural cytosine,while the obvious fluorescence quenching is observed by virtue of the excited state intermolecular charge transfer after pairing with 4acC,so it is supposed as a promising biosensor for monitoring the fluorescence changes in the absence or presence of the 4acC.Additionally,the impact of binding deoxyribose on photophysical properties is explored to guarantee the biological applicability of the bright G-analogs in real environment.展开更多
Bimetallic oxides are promising electrocatalysts due to their rich composition,facile synthesis,and favorable stability under oxidizing conditions.This paper innovatively proposes a strategy aimed at constructing a on...Bimetallic oxides are promising electrocatalysts due to their rich composition,facile synthesis,and favorable stability under oxidizing conditions.This paper innovatively proposes a strategy aimed at constructing a one-dimensional heterostructure(Fe–NiO/NiMoO_(4) nanoparticles/nanofibers).The strategy commences with the meticulous treatment of NiMoO_(4) nanofibers,utilizing in situ etching techniques to induce the formation of Prussian Blue Analog compounds.In this process,[Fe(CN)_(6)]^(3-)anions react with the NiMoO_(4) host layer to form a steady NiFe PBA.Subsequently,the surface/interface reconstituted NiMoO_(4) nanofibers undergo direct oxidation,leading to a reconfiguration of the surface structure and the formation of a unique Fe–NiO/NiMoO_(4) one-dimensional heterostructure.The catalyst showed markedly enhanced electrocatalytic performance for the oxygen evolution reaction.Density functional theory results reveal that the incorporation of Fe as a dopant dramatically reduces the Gibbs free energy associated with the rate-determining step in the oxygen evolution reaction pathway.This pivotal transformation directly lowers the activation energy barrier,thereby significantly enhancing electron transfer efficiency.展开更多
Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was in...Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was initially and widely adopted in antimalarial treatments.As scientific research steadily progressed,its latent potential role in the cardiovascular system gradually captured the attention of the global scientific community.Artemisinin and its derivatives can reportedly play a protective role in the cardiovascular system through various mechanisms,including anti-inflammatory,anti-angiogenic,antioxidant,and anti-fibrotic effects,as well as the regulation of blood lipids and blood pressure.In particular,they have shown promising therapeutic effects in models of cardiovascular diseases such as atherosclerosis,myocardial ischaemia,and cardiac hypertrophy.In addition,artemisinin and its derivatives can improve cardiovascular function and prevent cardiovascular injury by regulating signalling pathways closely related to cardiovascular disease,such as AMPK and NF-kB.Although numerous ex vivo and in vivo experiments have verified the potential role of artemisinin in treating cardiovascular diseases,systematic studies to comprehensively elucidate its specific mechanism of action remain scarce.Further exploration of the precise roles of artemisinin and its derivatives in cardiovascular disease therapy,along with their potential clinical applications,could offer valuable insights for future research and treatment strategies.展开更多
The India-Asia collision resulted in the formation of Qinghai-Tibet Plateau.Lower crustal flow model was proposed to explain the mechanism of Cenozoic tectonic deformation of Qinghai-Tibet Plateau.In this study,we pro...The India-Asia collision resulted in the formation of Qinghai-Tibet Plateau.Lower crustal flow model was proposed to explain the mechanism of Cenozoic tectonic deformation of Qinghai-Tibet Plateau.In this study,we propose a new approach by combining centrifugal analog modeling with numerical simulation to simulate the tectonic uplift history of the plateau based on the lower crustal flow model,and to investigate the material migration characteristics and the influence of crustal motion velocity and ductile layer viscosity on the plateau tectonic geomorphology.The models reproduce steep-sided flat-topped geomorphic features and clockwise rotation of the material at eastern Himalayan Syntaxis,verifying the rationality of the models.The results show that the greater the crustal motion velocity and the greater the ductile layer viscosity,the steeper the terrain change;and conversely,the smaller the crustal motion velocity and the smaller the ductile layer viscosity,the gentler the terrain change.This study further indicates that the weak lower crust plays an important role in the formation of geomorphic features and material migration characteristics of Qinghai-Tibet Plateau,and provides a new insight for the study of the uplift mechanism of the Tibetan Plateau.展开更多
The regioselective acylation of unprotected phenylethyl glucoside withcinnamoyl chloride leads to 6-OH cin-namoylated glucoside. In this manner, thirteen phenylpropanoidglycoside analogs were designed and prepared. Th...The regioselective acylation of unprotected phenylethyl glucoside withcinnamoyl chloride leads to 6-OH cin-namoylated glucoside. In this manner, thirteen phenylpropanoidglycoside analogs were designed and prepared. Their structure was confirmed by ~1H NMR and ^(13)CNMR spectra.展开更多
In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the trea...In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.展开更多
Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be contr...Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.展开更多
Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translo...Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translocation line 6VS/6AL. Amplified products were cloned and sequenced. Nine clones with NBS and one with serine/threonine kinase domain were obtained. The NBS clones were classified to six groups according to their nucleotide sequence identities (90% or higher). These resistance gene analogs (RGAs) all have open reading frames (ORF), and their amino acid sequences show high similarity to Yr10 in wheat, Mla1 and Mla6 in barley, RPS2 in Arabidopsis and other resistance (R) genes with conserved motifs. They were preliminarily mapped on the chromosomes of homoeologous groups 1, 2 and 5 of common wheat by nulli-tetrasomic analysis. The 5'-end sequence of an RGA N5 was obtained by 5'-RACE PCR. It encodes six leucine zipper (LZ) and has high sequence similarity to RPS2.展开更多
As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed...As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)HBV.The question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV replication.In the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of Nas.In the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion secretion.However,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV virions.Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.展开更多
Allatostatins （ASTs）, a family of insect neuropeptide, can inhibit juvenile hormone （JH） biosynthesis by the corpora allata （CA） in Diploptera punctata, and therefore be regarded as potential leads for the disco...Allatostatins （ASTs）, a family of insect neuropeptide, can inhibit juvenile hormone （JH） biosynthesis by the corpora allata （CA） in Diploptera punctata, and therefore be regarded as potential leads for the discovery of new insect growth regulators （1GRs）. But several shortcomings, such as their sensitivity to peptidases and high cost, impeded their practical application in pest management. In order to discover new IGRs, one AST analog B1 possessing non-peptide group was discovered with high ability to inhibit JH biosynthesis in vitro （IC50： 0.09 μmol/L） in our previous studies. In the present work, two series of B1 analogs with different substituents on the N-terminus region were designed and synthesized. The result suggested that benzene showed better activity than other heterocycles, and the para-substitution on the benzene was beneficial for activity. Moreover, analogs with logP value over 2.0 exhibited good activity, which indicated the hydrophobicity is important to the bioactivity. Three dimension quantitative structure-activity relationship （3D-QSAR） studies were performed to highlight the structural require- ments of ASTanalogs, which demonstrated introduction of bulkier substituents on the N-terminus would increase the activity. Analog Ⅱ12 （IC50： 0.08 μmol/L） exhibited similar inhibitory activity to the lead B1, but its synthetic route was simpler than B1. Therefore, Ⅱ12 could be used as a new lead compound for the discovery eco-friendly IGRs.展开更多
Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison o...Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.展开更多
objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral...objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral acid. Results Six chiral analogs of Baogongteng A were prepared. In mydriatic tests inrabbits, (+) - 32 - benzoyloxy - 6β - acetoxytropane and (+) - 32 - parachloro benzoyloxy- 6β- acetoxytropanepossess anticholinergic activities. Conclusion The configuration of enantiomers has significant influence on thebioactivity of analogs of Baogongteng A.展开更多
Sixteen novel oxazolidinone analogs containing substituted thiazole/fused-bicyclic（imidazo[ 1,2-b] pyridazine/ imidazo[2,1-b] thiazole） groups were designed and synthesized. A new method for the preparation of the k...Sixteen novel oxazolidinone analogs containing substituted thiazole/fused-bicyclic（imidazo[ 1,2-b] pyridazine/ imidazo[2,1-b] thiazole） groups were designed and synthesized. A new method for the preparation of the key intermediate compound 11 was proposed. The structures of the target compounds were confirmed by ^1H NMR, IR and MS, and their in vitro antibacterial activities against staphylococcus aureus were evaluated. Among them, compound 16a displays a promising antibacterial activity comparable to that of linezolid.展开更多
Insect growth regulators play an important role in integrated pest management strategies.The FGLa–allatostatins（ASTs）are a family of neuropeptides that can inhibit juvenile hormone（JH）biosynthesis by the corpora ...Insect growth regulators play an important role in integrated pest management strategies.The FGLa–allatostatins（ASTs）are a family of neuropeptides that can inhibit juvenile hormone（JH）biosynthesis by the corpora allata（CA）of Diploptera punctata in vitro,are regarded as insect growth regulator candidates.In the search for new potential mimics and to explore the effect of linker length on inhibiting JH biosynthesis,a series of AST analogs were synthesized by modifying the linker of K24,which was found to have a significant effect on JH biosynthesis in vitro in our previous study.Functional evaluation demonstrated that all the target compounds can activate the Dippu-Ast R,albeit with different potencies.Analog L6 with the longest linker（n=5）,exhibited not only a promising effect on inhibition of JH biosynthesis both in vitro and in vivo,but also good activity in inhibiting basal oocyte growth.Structure–activity relationships（SAR）studies showed that longer linkers provided greater contribution to activity.展开更多
Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to repo...Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin （CPT） and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin （1） and 10-hydroxycamptothecin （2） derivatives （1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e） were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua H＆#252;bner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.展开更多
The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL)analogs with various amides as donor molecules.The catalytic pe...The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL)analogs with various amides as donor molecules.The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure.The influences of reaction time,reaction temperature,and stirring speed on the catalytic performance were also investigated.Optimal reaction conditions comprised the reaction time of 1 h,the reaction temperature of 40°C,and the stirring speed of 1500 r·min-1.Under optimal condition,the n-C5 conversion,research octane number(RON)increment,total liquids yield,and isoparaffin yield in isomerized oil were56.80%,13.51,89.90 wt%,and 44.32 wt%,respectively.A new mathematical model was constructed to predict the relationships among RON increment,RON increment/n-C5 conversion ratio,and n-C5 conversion.The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%.Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3.The n-C5 conversion increased from 56.80%to 67.32%.The RON increment,total liquids yield,and isoparaffin yield reached 17.83,97.36 wt%,and 63.74 wt%,respectively.展开更多
A total of 11 novel combretastatin A-4（CA-4） analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes：（i）hydrogenated de...A total of 11 novel combretastatin A-4（CA-4） analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes：（i）hydrogenated derivatives,（ii） ethoxyl derivatives,（iii） amino derivatives and（iv） pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure–activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study.展开更多
A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susc...A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.展开更多
基金supported by the National Natural Science Foundation of China(52071083,52231007,12327804,52471224)Zhuhai Fudan Innovation Institute,and the Science and Technology Commission of Shanghai Municipality(23ZR1405000).
文摘By the random distribution of metals in a single phase,entropy engineering is applied to construct dense neighboring active centers with diverse electronic and geometric structures,realizing the continuous optimization of multiple primary reactions for oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Many catalysts developed through entropy engineering have been built in nearly equimolar ratios to pursue high entropy,hindering the identification of the active sites and potentially diluting the concentration of real active sites while weakening their electronic interactions with reaction intermediates.Herein,this work proposes an entropy-engineering strategy in metal nanoparticle-embedded nitrogen carbon electrocatalysts,implemented by entropy-engineered Prussian blue analogs(PBA)as precursors to enhance the catalytic activity of primary Cu-Fe active sites.Through the introduction of the micro-strains driven by entropy engineering,density functional theory(DFT)calculations and geometric phase analysis(GPA)using Lorentz electron microscopy further elucidate the optimization of the adsorption/desorption of intermediates.Furthermore,the multi-dimensional morphology and the size diminishment of the nanocrystals serve to expand the electrochemical area,maximizing the catalytic activity for both ORR and OER.Notably,the Zn-air battery assembled with CuFeCoNiZn-NC operated for over 1300 h with negligible decay.This work presents a paradigm for the design of low-cost electrocatalysts with entropy engineering for multi-step reactions.
基金supported by the National Natural Science Foundation of China(Grant Nos.12274265 and 11804195)the Natural Science Foundation of Shandong Province,China(Grant No.ZR2022MA006).
文摘The photophysical properties of fluorescent nucleobase analogs play a crucial role in nucleic acids detection and the investigation of their structural and functional characteristics.In this study,we computationally designed a series of quasiintrinsic fluorescent probes according to natural guanine(G)for selectively identifying covalent N^(4)-acetylcytosine(4acC),a base that is highly correlated with active transcription and gene expression.This work aims to gain insight into the role of 4acC in biological regulation with minimal perturbation to the native DNA structure.The results indicate that these Ganalogs possess extended π-conjugation in comparison with the natural guanine,which could yield efficient fluorescence emission and red-shifted absorption.Especially,the 8-thienyl-2’-deoxyguanosine(ThG)exhibits the highest fluorescence intensity and avoids self-absorption on account of the large Stokes shifts(>67 nm).What is more,the fluorescence of ThG is unaffected to base pairing with natural cytosine,while the obvious fluorescence quenching is observed by virtue of the excited state intermolecular charge transfer after pairing with 4acC,so it is supposed as a promising biosensor for monitoring the fluorescence changes in the absence or presence of the 4acC.Additionally,the impact of binding deoxyribose on photophysical properties is explored to guarantee the biological applicability of the bright G-analogs in real environment.
基金supported by the National Natural Science Foundation of China(52203257)Natural Science Foundation of Heilongjiang Province(YQ2022B008).
文摘Bimetallic oxides are promising electrocatalysts due to their rich composition,facile synthesis,and favorable stability under oxidizing conditions.This paper innovatively proposes a strategy aimed at constructing a one-dimensional heterostructure(Fe–NiO/NiMoO_(4) nanoparticles/nanofibers).The strategy commences with the meticulous treatment of NiMoO_(4) nanofibers,utilizing in situ etching techniques to induce the formation of Prussian Blue Analog compounds.In this process,[Fe(CN)_(6)]^(3-)anions react with the NiMoO_(4) host layer to form a steady NiFe PBA.Subsequently,the surface/interface reconstituted NiMoO_(4) nanofibers undergo direct oxidation,leading to a reconfiguration of the surface structure and the formation of a unique Fe–NiO/NiMoO_(4) one-dimensional heterostructure.The catalyst showed markedly enhanced electrocatalytic performance for the oxygen evolution reaction.Density functional theory results reveal that the incorporation of Fe as a dopant dramatically reduces the Gibbs free energy associated with the rate-determining step in the oxygen evolution reaction pathway.This pivotal transformation directly lowers the activation energy barrier,thereby significantly enhancing electron transfer efficiency.
基金supported by the Youth Natural Science Foundation of Shandong Province(grant number:ZR2022QH340).
文摘Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was initially and widely adopted in antimalarial treatments.As scientific research steadily progressed,its latent potential role in the cardiovascular system gradually captured the attention of the global scientific community.Artemisinin and its derivatives can reportedly play a protective role in the cardiovascular system through various mechanisms,including anti-inflammatory,anti-angiogenic,antioxidant,and anti-fibrotic effects,as well as the regulation of blood lipids and blood pressure.In particular,they have shown promising therapeutic effects in models of cardiovascular diseases such as atherosclerosis,myocardial ischaemia,and cardiac hypertrophy.In addition,artemisinin and its derivatives can improve cardiovascular function and prevent cardiovascular injury by regulating signalling pathways closely related to cardiovascular disease,such as AMPK and NF-kB.Although numerous ex vivo and in vivo experiments have verified the potential role of artemisinin in treating cardiovascular diseases,systematic studies to comprehensively elucidate its specific mechanism of action remain scarce.Further exploration of the precise roles of artemisinin and its derivatives in cardiovascular disease therapy,along with their potential clinical applications,could offer valuable insights for future research and treatment strategies.
基金supported by Excellent Research Group Project for Multiphase Evolution in Hyper-Gravity of the National Natural Science Foundation of China(No.52588202)。
文摘The India-Asia collision resulted in the formation of Qinghai-Tibet Plateau.Lower crustal flow model was proposed to explain the mechanism of Cenozoic tectonic deformation of Qinghai-Tibet Plateau.In this study,we propose a new approach by combining centrifugal analog modeling with numerical simulation to simulate the tectonic uplift history of the plateau based on the lower crustal flow model,and to investigate the material migration characteristics and the influence of crustal motion velocity and ductile layer viscosity on the plateau tectonic geomorphology.The models reproduce steep-sided flat-topped geomorphic features and clockwise rotation of the material at eastern Himalayan Syntaxis,verifying the rationality of the models.The results show that the greater the crustal motion velocity and the greater the ductile layer viscosity,the steeper the terrain change;and conversely,the smaller the crustal motion velocity and the smaller the ductile layer viscosity,the gentler the terrain change.This study further indicates that the weak lower crust plays an important role in the formation of geomorphic features and material migration characteristics of Qinghai-Tibet Plateau,and provides a new insight for the study of the uplift mechanism of the Tibetan Plateau.
文摘The regioselective acylation of unprotected phenylethyl glucoside withcinnamoyl chloride leads to 6-OH cin-namoylated glucoside. In this manner, thirteen phenylpropanoidglycoside analogs were designed and prepared. Their structure was confirmed by ~1H NMR and ^(13)CNMR spectra.
文摘In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.
文摘Piceatannol, (E)-3, 3, 4, 5-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.
文摘Two pairs of degenerate primers were designed based on nucleotide-binding site (NBS) and serine/threonine kinase domain. PCR was performed with the primers and cDNA from the Triticum aestivum-Haynaldia villosa translocation line 6VS/6AL. Amplified products were cloned and sequenced. Nine clones with NBS and one with serine/threonine kinase domain were obtained. The NBS clones were classified to six groups according to their nucleotide sequence identities (90% or higher). These resistance gene analogs (RGAs) all have open reading frames (ORF), and their amino acid sequences show high similarity to Yr10 in wheat, Mla1 and Mla6 in barley, RPS2 in Arabidopsis and other resistance (R) genes with conserved motifs. They were preliminarily mapped on the chromosomes of homoeologous groups 1, 2 and 5 of common wheat by nulli-tetrasomic analysis. The 5'-end sequence of an RGA N5 was obtained by 5'-RACE PCR. It encodes six leucine zipper (LZ) and has high sequence similarity to RPS2.
基金supported by the Deutsche Forschungsgemeinschaft (TRR60)the National Nature Science Foundation of China (31770180, 31621061)+1 种基金the Youth Innovation Promotion Association CAS (No. 2016303)the Youth Planning Project of Hubei Health Planning Commission (WJ2017Q027)
文摘As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)HBV.The question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV replication.In the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of Nas.In the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion secretion.However,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV virions.Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.
基金financially supported by the National Natural Science Foundation of China(No.21372257)the grants from the National Key Research and Development Plan(No.2017YFD0200504)
文摘Allatostatins （ASTs）, a family of insect neuropeptide, can inhibit juvenile hormone （JH） biosynthesis by the corpora allata （CA） in Diploptera punctata, and therefore be regarded as potential leads for the discovery of new insect growth regulators （1GRs）. But several shortcomings, such as their sensitivity to peptidases and high cost, impeded their practical application in pest management. In order to discover new IGRs, one AST analog B1 possessing non-peptide group was discovered with high ability to inhibit JH biosynthesis in vitro （IC50： 0.09 μmol/L） in our previous studies. In the present work, two series of B1 analogs with different substituents on the N-terminus region were designed and synthesized. The result suggested that benzene showed better activity than other heterocycles, and the para-substitution on the benzene was beneficial for activity. Moreover, analogs with logP value over 2.0 exhibited good activity, which indicated the hydrophobicity is important to the bioactivity. Three dimension quantitative structure-activity relationship （3D-QSAR） studies were performed to highlight the structural require- ments of ASTanalogs, which demonstrated introduction of bulkier substituents on the N-terminus would increase the activity. Analog Ⅱ12 （IC50： 0.08 μmol/L） exhibited similar inhibitory activity to the lead B1, but its synthetic route was simpler than B1. Therefore, Ⅱ12 could be used as a new lead compound for the discovery eco-friendly IGRs.
基金supported by the National Natural Science Foundation of China(Molecular design,catalysis and synthesis methods of novel fentanyl analogs active compounds)No.20872095
文摘Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.
文摘objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral acid. Results Six chiral analogs of Baogongteng A were prepared. In mydriatic tests inrabbits, (+) - 32 - benzoyloxy - 6β - acetoxytropane and (+) - 32 - parachloro benzoyloxy- 6β- acetoxytropanepossess anticholinergic activities. Conclusion The configuration of enantiomers has significant influence on thebioactivity of analogs of Baogongteng A.
文摘Sixteen novel oxazolidinone analogs containing substituted thiazole/fused-bicyclic（imidazo[ 1,2-b] pyridazine/ imidazo[2,1-b] thiazole） groups were designed and synthesized. A new method for the preparation of the key intermediate compound 11 was proposed. The structures of the target compounds were confirmed by ^1H NMR, IR and MS, and their in vitro antibacterial activities against staphylococcus aureus were evaluated. Among them, compound 16a displays a promising antibacterial activity comparable to that of linezolid.
基金supported by the National Natural Science Foundation of China (No. 21372257)the National Basic Research Program of China (973 Program, No. 2010CB126104)+1 种基金the Natural Sciences and Engineering Research Council of Canadasupported by China Scholarship Council (CSC) to study in the laboratory of SST at University of Toronto,Canada
文摘Insect growth regulators play an important role in integrated pest management strategies.The FGLa–allatostatins（ASTs）are a family of neuropeptides that can inhibit juvenile hormone（JH）biosynthesis by the corpora allata（CA）of Diploptera punctata in vitro,are regarded as insect growth regulator candidates.In the search for new potential mimics and to explore the effect of linker length on inhibiting JH biosynthesis,a series of AST analogs were synthesized by modifying the linker of K24,which was found to have a significant effect on JH biosynthesis in vitro in our previous study.Functional evaluation demonstrated that all the target compounds can activate the Dippu-Ast R,albeit with different potencies.Analog L6 with the longest linker（n=5）,exhibited not only a promising effect on inhibition of JH biosynthesis both in vitro and in vivo,but also good activity in inhibiting basal oocyte growth.Structure–activity relationships（SAR）studies showed that longer linkers provided greater contribution to activity.
基金supported by the National Natural Science Foundation of China (31171878,31071707 and 31000851)
文摘Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin （CPT） and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin （1） and 10-hydroxycamptothecin （2） derivatives （1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e） were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua H＆#252;bner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.
基金Supported by the National Natural Science Foundation of China(21802047)the Scientific Research Funds of Huaqiao University(600005-Z17Y0073).
文摘The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL)analogs with various amides as donor molecules.The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure.The influences of reaction time,reaction temperature,and stirring speed on the catalytic performance were also investigated.Optimal reaction conditions comprised the reaction time of 1 h,the reaction temperature of 40°C,and the stirring speed of 1500 r·min-1.Under optimal condition,the n-C5 conversion,research octane number(RON)increment,total liquids yield,and isoparaffin yield in isomerized oil were56.80%,13.51,89.90 wt%,and 44.32 wt%,respectively.A new mathematical model was constructed to predict the relationships among RON increment,RON increment/n-C5 conversion ratio,and n-C5 conversion.The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%.Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3.The n-C5 conversion increased from 56.80%to 67.32%.The RON increment,total liquids yield,and isoparaffin yield reached 17.83,97.36 wt%,and 63.74 wt%,respectively.
基金supported by the National Natural Science Foundation of China(Nos.21472126,21402122)Shanghai Municipal Natural Science Foundation(No.12ZR450200)
文摘A total of 11 novel combretastatin A-4（CA-4） analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes：（i）hydrogenated derivatives,（ii） ethoxyl derivatives,（iii） amino derivatives and（iv） pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure–activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study.
基金supported by Major R&D Program of New Drugs-National S&T Key Special Subject of China (No.2009ZX09103-115)National Natural Science Foundation of China(No.20872081)Natural Science Foundation of Shandong(No.Y2006C31)
文摘A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.
