Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their str...Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their structures were determined by comprehensive spectroscopic data,single-crystal X-ray diffraction analyses,and ECD calculations.In terms of structure,artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane-type sesquiterpenoid through four different[4+2]Diels−Alder cycloaddition models.Antihepatic fibrosis assay suggested that five compounds exhibited activity against HSC-LX2 with IC_(50)values ranging from 37.8 to 117.1μmol/L.The most active artemsieverolactone B(2)displayed significant inhibitory activity against HSC-LX2 with IC_(50)value of 37.8μmol/L,which was 3 times more active than the positive drug silybin(IC_(50),139.7μmol/L).Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen typeⅠ(ColⅠ),human hyaluronic acid(HA),and human laminin(HL)with IC_(50)values of 40.4μmol/L(Col I),55.1μmol/L(HL),47.3μmol/L(HA),which was 2 to 3-fold more potent than silybin.展开更多
Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong abi...Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong ability to produce numbers of secondary metabolites.However,this strain mainly produce rubratoxins alone with high yield in varied culture conditions,suggested most gene clusters are silent.Efforts for mining the cryptic gene clusters in P.dangeardii,including epigenetic regulation and one-strain-many-compounds(OSMAC)approach were failed probably due to the high yield of rubratoxins.A metabolic shunting strategy by deleting the key gene for rubratoxins biosynthesis combining with optimization of culture condition successfully activated multiple silent genes encoding for other polyketide synthases(PKSs),and led to the trace compounds detectable.As a result,a total of 23 new compounds including azaphilone monomers,dimers,turimers with unprecedented polycyclic bridged heterocycle and spiral structures,as well as siderophores were identified.Some compounds showed significant cytotoxicities,anti-inflammatory or antioxidant activities.The attractive dual PKS s gene clusters for azaphilones biosynthesis were mined by bioinformatic analysis and overexpression of a pathway specific transcription factor.Our work therefor provides an efficient approach to mine the chemical diversity of endophytic fungi.展开更多
A series of copolymers of thiazoloisoindigo (Tzll) with different chalcogenophene trimers were synthesized to systematicllyinvestigate the chalcogen effect on their charge transport propertes.When only the middlethiop...A series of copolymers of thiazoloisoindigo (Tzll) with different chalcogenophene trimers were synthesized to systematicllyinvestigate the chalcogen effect on their charge transport propertes.When only the middlethiophene ring of terthiphene(T-T-T)is replaced byheavier chalcogenophenes,a preference(expressed by the ratio of μe/μh)towards electron transport was observed descending from T-T-Tto T-Se-Tthen to T-Te-T(Se and Te stand for selenophene and tellurophene,respectively).On the other hand,with the increased number of heavierchalcogenophenes,a preference toward hole transport was observed descending from Se-T-Se to Se-Se-se then to Se-Te-Se.This phenomenon iswellexplained by the balance between the aromatic resonance energy of the chalcogenophenes and the electronegativity of the chalcogens.Specifically,P(TZll-T-Se-T)displayed relatively balanced ambipolar property(μh^(max)andμe^(max) of 3.77 and 1.59 cm^(2)·v^(-1)·s^(-1)with aμe/μh of 0.42).while P(Tll-Se-Te-Se)exhibited the best preference to hole transfer with a u.u,of 0.09.P(Tzll-T-Te-T)exhibited the best preference to electrontransfer with aμe/μl,of 16 and theμe^(max)of 0.64 cm^(2)·v^(-).s^(-1)which is the highest electron mobility among the known conjugated polymerscontaining tellurophenes.展开更多
Electronic properties, such as HOMO and LUMO energies, band gaps, ionization potential （IP） and electron affinity （EA） of 2,7- and 3,6-1inked carbazole trimers, two conjugated oligomcrs with different linkages of ...Electronic properties, such as HOMO and LUMO energies, band gaps, ionization potential （IP） and electron affinity （EA） of 2,7- and 3,6-1inked carbazole trimers, two conjugated oligomcrs with different linkages of carbazole, were studicd by the density functional theory with Becke-Lee-Young-Parr composite exchange correlation functional （B3LYP）. The absorption spectra of these compounds were also investigated by time-dependent density functional theory （TD-DFT） with 6-3 IG＊ basis set. The calculated results indicated that the HOMO and LUMO of the 2,7- and 3,6-1inked carbazole trimers are both slightly destabilized on going from methyl substitution to sec-butyl substitution. Both IP and EA exhibit their good hole-transporting but poor electronaccepting ability. The presence of alkyl groups on the nitrogen atoms does not affect the intra-chain electronic delocalization along the molecular frame. Thus no significant effect on the band gap and absorption spectra of compounds has been found.展开更多
Plants have so much to offer as far as the discovery of new bioactive molecules is concerned.Among the several classes of phytochemicals,xanthones offer greater structural diversity and pharmacological value.They are ...Plants have so much to offer as far as the discovery of new bioactive molecules is concerned.Among the several classes of phytochemicals,xanthones offer greater structural diversity and pharmacological value.They are variable but definitely antioxidant in nature.Thus they are attractive targets for natural product and medicinal chemists.Xanthones and their glycosides possess broad spectrum interesting biological activities,such as cytotoxic,anti-inflammatory,antioxidant,anti-bacterial,neuroprotective,anti-HIV,enzyme inhibition,and hypoglycemic.The radical scavenging ability of these molecules accounts for most of their added therapeutic values.This paper intended to serve as a guide for future endeavors in quest for these molecules.Structure-Activity Relationship(SAR)and mechanism of action is given for better understanding of their role as pharmacological agents.The most recent advances in the isolation of bioactive xanthones and their glycosides were presented here.This paper will assist in directed approaches towards the discovery of analogues of xanthones.展开更多
4-Hydroxycinnamic acid derivatives,including ferulic acid (FA) (1),sinapic acid (SA) (2) and caffeic acid (CA) (3),are widely distributed in the plant kingdom,and undergo oxidative cross-coupling leading to the corres...4-Hydroxycinnamic acid derivatives,including ferulic acid (FA) (1),sinapic acid (SA) (2) and caffeic acid (CA) (3),are widely distributed in the plant kingdom,and undergo oxidative cross-coupling leading to the corresponding dehydrodimers,trimers and even higher oligomers in plants. In order to evaluate the antioxidative ability of these 4-hydroxycinnamic acid derivatives and their oligomers,we synthesized 8-8'-bis-lactone-dimers (8-8'-DiFA (4),8-8'-DiSA (5) and 8-8'-DiCA (6)),as well as a new trimer (7),by the reaction of the corresponding monomers (1-3) with Ag2O in methanol,and assayed their free radical-scavenging activity by the reaction with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·). It was found that CA (3) and 8-8'-DiCA (6) bearing o-dihydroxyl groups exhibited significantly higher radical-scavenging activity than those bearing no such groups,and oxidative coupling of CA (3) resulted in remarkable enhancement in the activity.展开更多
Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain...Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain valuable insights into how we might be able to harness these interesting biological molecules to construct complex nanostructures and materials. Uracil and thymine derivatives have been reported for use in biological applications and in self-assembling triple hydrogen bonded systems. Either uracil or thymine possesses three binding sites （Site 1, Site 2, and Site 3） that can induce strong directional N-H...O=C hydrogen bonding interaction. In this paper, theoretical calculations are carded out on the structural features and binding energies of hydrogen-bonded dimers and trimers formed by uracil and thymine bases. We find that the hydrogen bonds formed through Site 1 are the strongest, those formed through Site 3 are next, while those formed through Site 2 are the weakest. The atoms in molecules analysis show that the electron densities at the bond critical points and the corresponding Laplacians have greater values for those hydrogen bonds formed through Site 1 than through Site 2. All these results indicate that a uracil （or thymine） would interact with another uracil or thymine most likely through Site 1 and least likely through Site 2. We also find that a simple summation rule roughly exists for the binding energies in these dimers and trimers.展开更多
Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In...Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In order to well understand their MS fragmentation behaviors,they were investigated by electrospray ionization ion-trap time-of-flight multistage product ion mass spectrometry(ESI-IT-TOF-MSn)for the first time.The protonated molecules([M?H]?)of swerilactones J and K,and deprotonated molecules([M-H]-)of swerilactones H,J and K were readily observed in the conventional single-stage mass spectra(MS);however only the[M?Cl]-ion for swerilactone I was obtained in negative mode.Based on the MSn study,the fragmentation pathways of swerilactones H and I in negative mode,and swerilactones J and K in both positive and negative modes were proposed.The neutral losses of H_(2)O,CO,CO_(2)and C_(2)H_(4)O moieties are the particular elimination from the precursor ions due to the presence of hydroxyl,d-lactone and 1-O-ethyl moieties in their structures,of which the retro-Diels–Alder cleavage was the most particular dissociation.The fragment ions at m/z 341 and 291 in negative mode can be considered as the diagnostic ions for secoiridoid trimers.This investigation will provide valuable information for their fast characterization from complicated natural mixtures and extensive understanding their structural architectures.展开更多
In this work,we study environment-assisted excitation energy transfer(EET) through calculating energy transfer efficiency(ETE) in LH1-RC-type and LH2-type trimers,which can be used to mimic energy transfer behaviors i...In this work,we study environment-assisted excitation energy transfer(EET) through calculating energy transfer efficiency(ETE) in LH1-RC-type and LH2-type trimers,which can be used to mimic energy transfer behaviors in the basic unit cells of LH1-RC and LH2 light-harvesting complexes.Quantum state evolution of the trimers is described by a non-Hermitian quantum master equation.ETE in these trimer systems is investigated by the use of numerical solutions at finite temperatures for the non-Hermitian master equation.We theoretically reveal the temperature-assisted ETE enhancement.It is found that highly efficient EET with nearly unit efficiency may occur in the nearby regime of the critical point of quantum phase transition.展开更多
Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immun...Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.展开更多
Sometimes crystals cannot diffract X-rays beyond 3.0Åresolution due to the intrinsic flexibility associated with the protein.Low resolution diffraction data not only pose a challenge to structure determination,bu...Sometimes crystals cannot diffract X-rays beyond 3.0Åresolution due to the intrinsic flexibility associated with the protein.Low resolution diffraction data not only pose a challenge to structure determination,but also hamper interpretation of mechanistic details.Crystals of a 25.6 kDa non-Pfam,hypothetical protein,PF2046,diffracted X-rays to 3.38Åresolution.A combination of SeMet derived heavy atom positions with multiple cycles of B-factor sharpening,multi-crystal averaging,restrained refinement followed by manual inspection of electron density and model building resulted in a final model with a R value of 23.5(R_(free)=24.7).The asymmetric unit was large and consisted of six molecules arranged as a homodimer of trimers.Analysis of the structure revealed the presence of a RNA binding domain suggesting a role for PF2046 in the processing of nucleic acids.展开更多
The development of high-efficiency and cost-effective bifunctional electrocatalysts for overall water splitting remains a formidable challenge.Herein,FeNi-Nd_(2)O_(3) nanoparticles anchored on N-doped carbon nanotubes...The development of high-efficiency and cost-effective bifunctional electrocatalysts for overall water splitting remains a formidable challenge.Herein,FeNi-Nd_(2)O_(3) nanoparticles anchored on N-doped carbon nanotubes(FeNi-Nd_(2)O_(3)/NCN) are designed for highly effective overall water splitting via a facile two-step hydrothermal approach.The synthetic FeNi-Nd_(2)O_(3) hetero-trimers(Fe 2p-Ni 2p-Nd 3d orbital coupling)on NCN achieve excellent oxygen evolution reaction(OER) and hydrogen evolution reaction(HER) activities with overpotentials of 270 and 120 mV at 10 mA cm^(-2) in 1 M KOH solution.Moreover,a small voltage of 1.52 V at 10 mA cm^(-2) is achieved when FeNi-Nd_(2)O_(3)/NCN is assessed as bifunctional catalyst for overall water splitting,which is superior to the typically integrated Pt/C and RuO_(2) counterparts(1.54 V at 10 mA cm^(-2)).The related characterizations including X-ray absorption fine structure(XAFS)spectroscopy show that the remarkably improved activity is originated from Nd_(2)O_(3)-induced FeNi bimetallic lattice contraction.Furthermore,density functional theory(DFT) calculations indicate that the lattice contraction reduces binding energies of intermediates by downshifting the position of FeNi bimetallic d-band center relative to the Fermi level to optimize catalytic performance.Therefore,the Nd_(2)O_(3)-induced FeNi bimetallic lattice contraction may provide a new perspective for designing and synthesizing innovative catalytic systems.展开更多
基金supported by the Key Program of National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+1 种基金the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021).
文摘Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their structures were determined by comprehensive spectroscopic data,single-crystal X-ray diffraction analyses,and ECD calculations.In terms of structure,artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane-type sesquiterpenoid through four different[4+2]Diels−Alder cycloaddition models.Antihepatic fibrosis assay suggested that five compounds exhibited activity against HSC-LX2 with IC_(50)values ranging from 37.8 to 117.1μmol/L.The most active artemsieverolactone B(2)displayed significant inhibitory activity against HSC-LX2 with IC_(50)value of 37.8μmol/L,which was 3 times more active than the positive drug silybin(IC_(50),139.7μmol/L).Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen typeⅠ(ColⅠ),human hyaluronic acid(HA),and human laminin(HL)with IC_(50)values of 40.4μmol/L(Col I),55.1μmol/L(HL),47.3μmol/L(HA),which was 2 to 3-fold more potent than silybin.
基金supported financially by the National Key Research and Development Program of China(2018YFA0901900)the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-010,2017-I2M-4-004)+1 种基金Fundamental Research Funds for the Central Universities(2017PT35001)supported by the Drug Innovation Major Project(2018ZX09711001-008-001)
文摘Endophytic fungi are promising producers of bioactive small molecules.Bioinformatic analysis of the genome of an endophytic fungus Penicillium dangeardii revealed 43 biosynthetic gene clusters,exhibited its strong ability to produce numbers of secondary metabolites.However,this strain mainly produce rubratoxins alone with high yield in varied culture conditions,suggested most gene clusters are silent.Efforts for mining the cryptic gene clusters in P.dangeardii,including epigenetic regulation and one-strain-many-compounds(OSMAC)approach were failed probably due to the high yield of rubratoxins.A metabolic shunting strategy by deleting the key gene for rubratoxins biosynthesis combining with optimization of culture condition successfully activated multiple silent genes encoding for other polyketide synthases(PKSs),and led to the trace compounds detectable.As a result,a total of 23 new compounds including azaphilone monomers,dimers,turimers with unprecedented polycyclic bridged heterocycle and spiral structures,as well as siderophores were identified.Some compounds showed significant cytotoxicities,anti-inflammatory or antioxidant activities.The attractive dual PKS s gene clusters for azaphilones biosynthesis were mined by bioinformatic analysis and overexpression of a pathway specific transcription factor.Our work therefor provides an efficient approach to mine the chemical diversity of endophytic fungi.
基金the National Natural Science Foundation of China(Nos.22075105 and 51573204)National Science Foundation of Shandong Province(No.ZR2018ZB0315)+1 种基金H.Zhang thanks the financial support from the National Natural Science Foundation of China(No.51803230)Prof.J.Wang thanks the financial support from the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education,Jianghan University.The authors thank Dr.Chunming Yang for GIWAXS tests and beamline BL16B1(Shanghai Synchrotron Radiation Facility)for providing beam time.
文摘A series of copolymers of thiazoloisoindigo (Tzll) with different chalcogenophene trimers were synthesized to systematicllyinvestigate the chalcogen effect on their charge transport propertes.When only the middlethiophene ring of terthiphene(T-T-T)is replaced byheavier chalcogenophenes,a preference(expressed by the ratio of μe/μh)towards electron transport was observed descending from T-T-Tto T-Se-Tthen to T-Te-T(Se and Te stand for selenophene and tellurophene,respectively).On the other hand,with the increased number of heavierchalcogenophenes,a preference toward hole transport was observed descending from Se-T-Se to Se-Se-se then to Se-Te-Se.This phenomenon iswellexplained by the balance between the aromatic resonance energy of the chalcogenophenes and the electronegativity of the chalcogens.Specifically,P(TZll-T-Se-T)displayed relatively balanced ambipolar property(μh^(max)andμe^(max) of 3.77 and 1.59 cm^(2)·v^(-1)·s^(-1)with aμe/μh of 0.42).while P(Tll-Se-Te-Se)exhibited the best preference to hole transfer with a u.u,of 0.09.P(Tzll-T-Te-T)exhibited the best preference to electrontransfer with aμe/μl,of 16 and theμe^(max)of 0.64 cm^(2)·v^(-).s^(-1)which is the highest electron mobility among the known conjugated polymerscontaining tellurophenes.
基金The project was supported by the Scientific Research Fund of Hunan Provincial Education Department (No. 05A002)the Prominent Mid-youth Science and Technology Foundation of Hunan Province (No. 04JJ1010)
文摘Electronic properties, such as HOMO and LUMO energies, band gaps, ionization potential （IP） and electron affinity （EA） of 2,7- and 3,6-1inked carbazole trimers, two conjugated oligomcrs with different linkages of carbazole, were studicd by the density functional theory with Becke-Lee-Young-Parr composite exchange correlation functional （B3LYP）. The absorption spectra of these compounds were also investigated by time-dependent density functional theory （TD-DFT） with 6-3 IG＊ basis set. The calculated results indicated that the HOMO and LUMO of the 2,7- and 3,6-1inked carbazole trimers are both slightly destabilized on going from methyl substitution to sec-butyl substitution. Both IP and EA exhibit their good hole-transporting but poor electronaccepting ability. The presence of alkyl groups on the nitrogen atoms does not affect the intra-chain electronic delocalization along the molecular frame. Thus no significant effect on the band gap and absorption spectra of compounds has been found.
基金funding support from the National Natural Science Foundation of China (No. 81673579)Hunan Province Universities 2011 Collaborative Innovation Center of Protection and Utilization of Hu-Xiang Chinese Medicine ResourcesHunan Provincial Key Laboratory of Diagnostics in Chinese Medicine
文摘Plants have so much to offer as far as the discovery of new bioactive molecules is concerned.Among the several classes of phytochemicals,xanthones offer greater structural diversity and pharmacological value.They are variable but definitely antioxidant in nature.Thus they are attractive targets for natural product and medicinal chemists.Xanthones and their glycosides possess broad spectrum interesting biological activities,such as cytotoxic,anti-inflammatory,antioxidant,anti-bacterial,neuroprotective,anti-HIV,enzyme inhibition,and hypoglycemic.The radical scavenging ability of these molecules accounts for most of their added therapeutic values.This paper intended to serve as a guide for future endeavors in quest for these molecules.Structure-Activity Relationship(SAR)and mechanism of action is given for better understanding of their role as pharmacological agents.The most recent advances in the isolation of bioactive xanthones and their glycosides were presented here.This paper will assist in directed approaches towards the discovery of analogues of xanthones.
基金supported by the National Natural Science Foundation of China (20972063 and 20621091)the 111 ProjectProgram for New Century Excellent Talents in University (NCET-06-0906)
文摘4-Hydroxycinnamic acid derivatives,including ferulic acid (FA) (1),sinapic acid (SA) (2) and caffeic acid (CA) (3),are widely distributed in the plant kingdom,and undergo oxidative cross-coupling leading to the corresponding dehydrodimers,trimers and even higher oligomers in plants. In order to evaluate the antioxidative ability of these 4-hydroxycinnamic acid derivatives and their oligomers,we synthesized 8-8'-bis-lactone-dimers (8-8'-DiFA (4),8-8'-DiSA (5) and 8-8'-DiCA (6)),as well as a new trimer (7),by the reaction of the corresponding monomers (1-3) with Ag2O in methanol,and assayed their free radical-scavenging activity by the reaction with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·). It was found that CA (3) and 8-8'-DiCA (6) bearing o-dihydroxyl groups exhibited significantly higher radical-scavenging activity than those bearing no such groups,and oxidative coupling of CA (3) resulted in remarkable enhancement in the activity.
基金supported by the National Natural Science Foundation of China (20973088)the Educational Department of Liaoning Province (2007T091, 2008T106)
文摘Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain valuable insights into how we might be able to harness these interesting biological molecules to construct complex nanostructures and materials. Uracil and thymine derivatives have been reported for use in biological applications and in self-assembling triple hydrogen bonded systems. Either uracil or thymine possesses three binding sites （Site 1, Site 2, and Site 3） that can induce strong directional N-H...O=C hydrogen bonding interaction. In this paper, theoretical calculations are carded out on the structural features and binding energies of hydrogen-bonded dimers and trimers formed by uracil and thymine bases. We find that the hydrogen bonds formed through Site 1 are the strongest, those formed through Site 3 are next, while those formed through Site 2 are the weakest. The atoms in molecules analysis show that the electron densities at the bond critical points and the corresponding Laplacians have greater values for those hydrogen bonds formed through Site 1 than through Site 2. All these results indicate that a uracil （or thymine） would interact with another uracil or thymine most likely through Site 1 and least likely through Site 2. We also find that a simple summation rule roughly exists for the binding energies in these dimers and trimers.
文摘Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In order to well understand their MS fragmentation behaviors,they were investigated by electrospray ionization ion-trap time-of-flight multistage product ion mass spectrometry(ESI-IT-TOF-MSn)for the first time.The protonated molecules([M?H]?)of swerilactones J and K,and deprotonated molecules([M-H]-)of swerilactones H,J and K were readily observed in the conventional single-stage mass spectra(MS);however only the[M?Cl]-ion for swerilactone I was obtained in negative mode.Based on the MSn study,the fragmentation pathways of swerilactones H and I in negative mode,and swerilactones J and K in both positive and negative modes were proposed.The neutral losses of H_(2)O,CO,CO_(2)and C_(2)H_(4)O moieties are the particular elimination from the precursor ions due to the presence of hydroxyl,d-lactone and 1-O-ethyl moieties in their structures,of which the retro-Diels–Alder cleavage was the most particular dissociation.The fragment ions at m/z 341 and 291 in negative mode can be considered as the diagnostic ions for secoiridoid trimers.This investigation will provide valuable information for their fast characterization from complicated natural mixtures and extensive understanding their structural architectures.
基金supported by the National Fundamental Research Program (Grant No. 2007CB925204)the National Natural Science Foundation of China (Grant Nos. 11075050 and 10775048)+1 种基金the Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT0964)the Hunan Provincial Natural Science Foundation (Grant No. 11JJ7001)
文摘In this work,we study environment-assisted excitation energy transfer(EET) through calculating energy transfer efficiency(ETE) in LH1-RC-type and LH2-type trimers,which can be used to mimic energy transfer behaviors in the basic unit cells of LH1-RC and LH2 light-harvesting complexes.Quantum state evolution of the trimers is described by a non-Hermitian quantum master equation.ETE in these trimer systems is investigated by the use of numerical solutions at finite temperatures for the non-Hermitian master equation.We theoretically reveal the temperature-assisted ETE enhancement.It is found that highly efficient EET with nearly unit efficiency may occur in the nearby regime of the critical point of quantum phase transition.
基金This work was supported by the National Natural Science Foundation of China(81672018,81561128008)the National Basic Research Program of China(973program#2014CB542502)+2 种基金the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)Shanghai Pujiang Program(19PJ1409100)Intramural Funding from Shanghai Public Health Clinical Center.
文摘Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.
基金This work was funded by the Ministry of Science and Technology of China(Grant Nos.2006AA02A316,2009DFB30310 and 2006CB910901)the National Natural Science Foundation of China(Grants Nos.30670427 and 30721003)+1 种基金the Ministry of Health of China(Grant No.2008ZX10404)CAS Research Grant(No.KSCX2-YW-R-127 and INFO-115-D01-2009).
文摘Sometimes crystals cannot diffract X-rays beyond 3.0Åresolution due to the intrinsic flexibility associated with the protein.Low resolution diffraction data not only pose a challenge to structure determination,but also hamper interpretation of mechanistic details.Crystals of a 25.6 kDa non-Pfam,hypothetical protein,PF2046,diffracted X-rays to 3.38Åresolution.A combination of SeMet derived heavy atom positions with multiple cycles of B-factor sharpening,multi-crystal averaging,restrained refinement followed by manual inspection of electron density and model building resulted in a final model with a R value of 23.5(R_(free)=24.7).The asymmetric unit was large and consisted of six molecules arranged as a homodimer of trimers.Analysis of the structure revealed the presence of a RNA binding domain suggesting a role for PF2046 in the processing of nucleic acids.
基金supported by the National Natural Science Foundation of China (NSFC) (52171206, 51762013)the Key Project of Hebei Natural Science Foundation (E20202201030)+5 种基金the BeijingTianjin-Hebei Collaborative Innovation Community Construction Project (21344301D)The Second Batch of Young Talent of Hebei Province (70280016160250, 70280011808)the Key Fund in Hebei Province Department of Education China (ZD2021014)The Central Government Guide Local Funding Projects for Scientific and Technological Development (216Z4404G, 206Z4402G)the Interdisciplinary Research Program of Natural Science of Hebei University (DXK202107)the China Postdoctoral Science Foundation (No. 2021M701718)。
文摘The development of high-efficiency and cost-effective bifunctional electrocatalysts for overall water splitting remains a formidable challenge.Herein,FeNi-Nd_(2)O_(3) nanoparticles anchored on N-doped carbon nanotubes(FeNi-Nd_(2)O_(3)/NCN) are designed for highly effective overall water splitting via a facile two-step hydrothermal approach.The synthetic FeNi-Nd_(2)O_(3) hetero-trimers(Fe 2p-Ni 2p-Nd 3d orbital coupling)on NCN achieve excellent oxygen evolution reaction(OER) and hydrogen evolution reaction(HER) activities with overpotentials of 270 and 120 mV at 10 mA cm^(-2) in 1 M KOH solution.Moreover,a small voltage of 1.52 V at 10 mA cm^(-2) is achieved when FeNi-Nd_(2)O_(3)/NCN is assessed as bifunctional catalyst for overall water splitting,which is superior to the typically integrated Pt/C and RuO_(2) counterparts(1.54 V at 10 mA cm^(-2)).The related characterizations including X-ray absorption fine structure(XAFS)spectroscopy show that the remarkably improved activity is originated from Nd_(2)O_(3)-induced FeNi bimetallic lattice contraction.Furthermore,density functional theory(DFT) calculations indicate that the lattice contraction reduces binding energies of intermediates by downshifting the position of FeNi bimetallic d-band center relative to the Fermi level to optimize catalytic performance.Therefore,the Nd_(2)O_(3)-induced FeNi bimetallic lattice contraction may provide a new perspective for designing and synthesizing innovative catalytic systems.
