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
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
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
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
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
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
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
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
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
BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent prog...BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog(NA)therapy.AIM The study aim was to clarify risk factors and the diagnostic value of alphafetoprotein(AFP)for HCC progression in NA-treated hepatitis B virus(HBV)-related cirrhosis patients.METHODS In this retrospective cross-sectional study,we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital.The patients were divided into two groups,145 who did not progress to HCC(No-HCC group),and 121 who progressed to HCC during NA treatment(HCC group).The logistic regression analysis was used to analyze the risk factors of HCC progression.The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed that age≥60 years(P=0.001),hepatitis B and alcoholic etiology(P=0.007),smoking history(P<0.001),family history of HBV-related HCC(P=0.002),lamivudine resistance(P=0.011),HBV DNA negative(P=0.023),aspartate aminotransferase>80 U/L(P=0.002),gamma-glutamyl transpeptidase>120 U/L(P=0.001),alkaline phosphatase>250 U/L(P=0.001),fasting blood glucose(FBG)≥6.16(mmol/L)(P=0.001)and Child-Pugh class C(P=0.005)were correlated with HCC progression.In multivariate analysis,age≥60 years[hazard ratio(HR)=3.089,95%confidence interval(CI):1.437-6.631,P=0.004],smoking history(HR=4.001,95%CI:1.836-8.716,P<0.01),family history of HBV-related HCC(HR=6.763,95%CI:1.253-36.499,P<0.05),lamivudine resistance(HR=2.949,95%CI:1.207-7.208,P=0.018),HBV DNA negative(HR=0.026,95%CI:0.007-0.139,P<0.01),FBG≥6.16 mmol/L(HR=7.219,95%CI:3.716-14.024,P<0.01)were independent risk factors of HCC progression.ROC of AFP for diagnosis of HCC was 0.746(95%CI:0.674-0.818).A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609,and specificity of 0.818 for diagnosing HCC.CONCLUSION Age≥60 years,smoking history,family history of HCC,lamivudine resistance,HBV DNA negative,FBG≥6.16 mmol/L were risk factors of HCC progression.Serum AFP had limited diagnostic value for HCC.展开更多
Aqueous sodium-ion batteries(ASIBs)and aqueous potassium-ion batteries(APIBs)present significant potential for large-scale energy storage due to their cost-effectiveness,safety,and environmental compatibility.Nonethel...Aqueous sodium-ion batteries(ASIBs)and aqueous potassium-ion batteries(APIBs)present significant potential for large-scale energy storage due to their cost-effectiveness,safety,and environmental compatibility.Nonetheless,the intricate energy storage mechanisms in aqueous electrolytes place stringent require-ments on the host materials.Prussian blue analogs(PBAs),with their open three-dimensional framework and facile synthesis,stand out as leading candidates for aqueous energy storage.However,PBAs possess a swift capacity fade and limited cycle longevity,for their structural integrity is compromised by the pronounced dis-solution of transition metal(TM)ions in the aqueous milieu.This manuscript provides an exhaustive review of the recent advancements concerning PBAs in ASIBs and APIBs.The dissolution mechanisms of TM ions in PBAs,informed by their structural attributes and redox processes,are thoroughly examined.Moreover,this study delves into innovative design tactics to alleviate the dissolution issue of TM ions.In conclusion,the paper consolidates various strategies for suppressing the dissolution of TM ions in PBAs and posits avenues for prospective exploration of high-safety aqueous sodium-/potassium-ion batteries.展开更多
Owing to frequent environmental monitoring of tetrabromobisphenol-A(TBBPA)analogs and their potential ecotoxicological effects on organisms,analysis of trace levels of TBBPA analogs with more non-polar and less water-...Owing to frequent environmental monitoring of tetrabromobisphenol-A(TBBPA)analogs and their potential ecotoxicological effects on organisms,analysis of trace levels of TBBPA analogs with more non-polar and less water-soluble characteristics is of great significance for studying their environmental behaviors and toxic effects.Herein,a fast and sensitive technique is developed for directly detecting aqueous TBBPA analogs,including TBBPA mono(allyl ether)(TBBPA-MAE),TBBPA mono(2,3-dibromopropyl ether)(TBBPAMDBPE),TBBPA mono(2-hydroxyethyl ether)(TBBPA-MHEE)and TBBPA mono(glycidyl ether)(TBBPAMGE),by combining solid phase microextraction(SPME)based on porous covalent organic frameworks(Porous-COFs)with constant flow desorption ionization-mass spectrometry(CFDI-MS).As chromatographic separation is replaced by constant flow desorption,each sample can be analyzed within 7 min.The hierarchical porous structures(microporous,mesoporous and macroporous)of COFs lead to the enhanced mass transfer and the easier accessibility of active sites to TBBPA analogs,so that the extraction efficiency is 2.3-3.6 times higher than pure microporous COFs,and far superior to commercial coatings.The detection limit and quantification limit of this method are 0.1-1 and 0.4-3.2 ng/L,respectively.Ultratrace levels of TBBPA analogs from 5.0 ng/L to 66 ng/L have been successfully detected in river and sea water samples,showing great potential for subsequent studies of their environmental behaviors and toxicological effects.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
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
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
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
BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconver...BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.展开更多
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.
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 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.
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.
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.
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.
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 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.
文摘BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog(NA)therapy.AIM The study aim was to clarify risk factors and the diagnostic value of alphafetoprotein(AFP)for HCC progression in NA-treated hepatitis B virus(HBV)-related cirrhosis patients.METHODS In this retrospective cross-sectional study,we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital.The patients were divided into two groups,145 who did not progress to HCC(No-HCC group),and 121 who progressed to HCC during NA treatment(HCC group).The logistic regression analysis was used to analyze the risk factors of HCC progression.The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed that age≥60 years(P=0.001),hepatitis B and alcoholic etiology(P=0.007),smoking history(P<0.001),family history of HBV-related HCC(P=0.002),lamivudine resistance(P=0.011),HBV DNA negative(P=0.023),aspartate aminotransferase>80 U/L(P=0.002),gamma-glutamyl transpeptidase>120 U/L(P=0.001),alkaline phosphatase>250 U/L(P=0.001),fasting blood glucose(FBG)≥6.16(mmol/L)(P=0.001)and Child-Pugh class C(P=0.005)were correlated with HCC progression.In multivariate analysis,age≥60 years[hazard ratio(HR)=3.089,95%confidence interval(CI):1.437-6.631,P=0.004],smoking history(HR=4.001,95%CI:1.836-8.716,P<0.01),family history of HBV-related HCC(HR=6.763,95%CI:1.253-36.499,P<0.05),lamivudine resistance(HR=2.949,95%CI:1.207-7.208,P=0.018),HBV DNA negative(HR=0.026,95%CI:0.007-0.139,P<0.01),FBG≥6.16 mmol/L(HR=7.219,95%CI:3.716-14.024,P<0.01)were independent risk factors of HCC progression.ROC of AFP for diagnosis of HCC was 0.746(95%CI:0.674-0.818).A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609,and specificity of 0.818 for diagnosing HCC.CONCLUSION Age≥60 years,smoking history,family history of HCC,lamivudine resistance,HBV DNA negative,FBG≥6.16 mmol/L were risk factors of HCC progression.Serum AFP had limited diagnostic value for HCC.
基金This work was supported by the National Natural Science Foundation of China(52373306,52172233,and 51832004)the Natural Science Foundation of Hubei Province(2023AFA053)the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(2021CXLH0007).
文摘Aqueous sodium-ion batteries(ASIBs)and aqueous potassium-ion batteries(APIBs)present significant potential for large-scale energy storage due to their cost-effectiveness,safety,and environmental compatibility.Nonetheless,the intricate energy storage mechanisms in aqueous electrolytes place stringent require-ments on the host materials.Prussian blue analogs(PBAs),with their open three-dimensional framework and facile synthesis,stand out as leading candidates for aqueous energy storage.However,PBAs possess a swift capacity fade and limited cycle longevity,for their structural integrity is compromised by the pronounced dis-solution of transition metal(TM)ions in the aqueous milieu.This manuscript provides an exhaustive review of the recent advancements concerning PBAs in ASIBs and APIBs.The dissolution mechanisms of TM ions in PBAs,informed by their structural attributes and redox processes,are thoroughly examined.Moreover,this study delves into innovative design tactics to alleviate the dissolution issue of TM ions.In conclusion,the paper consolidates various strategies for suppressing the dissolution of TM ions in PBAs and posits avenues for prospective exploration of high-safety aqueous sodium-/potassium-ion batteries.
基金financially supported by the National Natural Science Foundation of China(Nos.21922402,21976185)the Innovation Academy for Green Manufacture,Chinese Academy of Sciences(No.IAGM2020C20)。
文摘Owing to frequent environmental monitoring of tetrabromobisphenol-A(TBBPA)analogs and their potential ecotoxicological effects on organisms,analysis of trace levels of TBBPA analogs with more non-polar and less water-soluble characteristics is of great significance for studying their environmental behaviors and toxic effects.Herein,a fast and sensitive technique is developed for directly detecting aqueous TBBPA analogs,including TBBPA mono(allyl ether)(TBBPA-MAE),TBBPA mono(2,3-dibromopropyl ether)(TBBPAMDBPE),TBBPA mono(2-hydroxyethyl ether)(TBBPA-MHEE)and TBBPA mono(glycidyl ether)(TBBPAMGE),by combining solid phase microextraction(SPME)based on porous covalent organic frameworks(Porous-COFs)with constant flow desorption ionization-mass spectrometry(CFDI-MS).As chromatographic separation is replaced by constant flow desorption,each sample can be analyzed within 7 min.The hierarchical porous structures(microporous,mesoporous and macroporous)of COFs lead to the enhanced mass transfer and the easier accessibility of active sites to TBBPA analogs,so that the extraction efficiency is 2.3-3.6 times higher than pure microporous COFs,and far superior to commercial coatings.The detection limit and quantification limit of this method are 0.1-1 and 0.4-3.2 ng/L,respectively.Ultratrace levels of TBBPA analogs from 5.0 ng/L to 66 ng/L have been successfully detected in river and sea water samples,showing great potential for subsequent studies of their environmental behaviors and toxicological effects.
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.
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 (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(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The Shandong Province Natural Science Foundation,No.ZR2019PH052the National Key Research and Development Program of China,No.2017YFC0908104.
文摘BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.
