A series of novel pyrazole fused heterocyclic derivatives were synthesized via a two-step procedure or a one-pot two step method, and their catalytic DNA cleavage abilities and anti-BVDV activities were also evaluated...A series of novel pyrazole fused heterocyclic derivatives were synthesized via a two-step procedure or a one-pot two step method, and their catalytic DNA cleavage abilities and anti-BVDV activities were also evaluated. The results obtained indicated that compounds 3b-3c could catalyze the cleavage of supercoiled DNA （pUC 19 plasmid DNA） to nicked DNA under physiological conditions with high yields via a hydrolytic mechanism. The studies on anti-viral activities against bovine viral diarrhea virus （BVDV） demonstrated that some of the pyrazole derivatives showed pronounced anti-BVDV activity with interesting ECso values and no significant cytotoxicity. Among them, compound 31 showed the highest antiviral activity （ECso = 0.12 μmol/L） and was 10 fold more than that of the positive control ribavirin （ECso = 1.3 μmol/L）, which provided a potential candidate for the development of anti-BVDV agents.展开更多
RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progre...RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.展开更多
Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been d...Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.展开更多
A copper-bispyridylpyrrolide complex [Cu(PDPH)Cl](PDPH = 2,5-bis(2′-pyridyl)pyrrole) was synthesized and characterized. The complex crystallizes in the orthorhombic system with space group Pccn, a = 0.9016(3) nm, b =...A copper-bispyridylpyrrolide complex [Cu(PDPH)Cl](PDPH = 2,5-bis(2′-pyridyl)pyrrole) was synthesized and characterized. The complex crystallizes in the orthorhombic system with space group Pccn, a = 0.9016(3) nm, b = 1.0931(4) nm, c =2.5319(8) nm, and V = 2.4951(15) nm3. The copper center is situated in a square planar geometry. The interaction of the copper(II)complex with calf thymus DNA(CT-DNA) was investigated by electronic absorption, circular dichroism(CD) and fluorescence spectra. It is proposed that the complex binds to CT-DNA through groove binding mode. Nuclease activity of the complex was also studied by gel electrophoresis method. The complex can efficiently cleave supercoiled p BR322 DNA in the presence of ascorbate(H2A) via oxidative pathway. The preliminary mechanism of DNA cleavage by the complex with different inhibiting reagents indicates that the hydroxyl radicals were involved as the active species in the DNA cleavage process.展开更多
A new dinuclear complex, [Ag（L）（CH3CN）]2（ClO4）2·2H2O（L=2,3-di-2-pyridylquinoxaline）, was prepared and characterized by elemental analyses, IR spectroscopy, and single-crystal X-ray diffraction analyses. T...A new dinuclear complex, [Ag（L）（CH3CN）]2（ClO4）2·2H2O（L=2,3-di-2-pyridylquinoxaline）, was prepared and characterized by elemental analyses, IR spectroscopy, and single-crystal X-ray diffraction analyses. The interaction of the complex with calf thymus DNA（CT-DNA） was investigated by absorption, fluorescence spectroscopies, and viscosity measurement. The results suggested that the complex was bound to DNA via an intercalative mode. The intrinsic binding constant value Kb was found to be approximately 1.48×10^3 L·mol^-1. Moreover, the Ag（I） complex could cleave the plasmid pUC19 DNA from the supercoiled Form Ⅰto the nicked FormⅡ under irradiation at 365 nm.展开更多
SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants di...SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted comparisons.Here,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the wild-type.In addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to hACE2.We also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host cells.Furthermore,all variants'pseudoviruses we tested gained the ability to enter the animal ACE2-expressing cells.Especially the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral evolution.The insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.展开更多
We reported the synthesis of a simple bifunctional molecule and the interaction between this molecule and DNA were studied by UV and the DNA cleavage behavoior was determined by agarose gel electrophoresis.
The electrospray ionization mass spectrometry investigation showed that the binding sites of [ZnL]^2＋, where L is 2-[bis（2- aminoethyl）amino]ethanol, with oxidized insulin B chain are Phel, His5 and Arg22, which le...The electrospray ionization mass spectrometry investigation showed that the binding sites of [ZnL]^2＋, where L is 2-[bis（2- aminoethyl）amino]ethanol, with oxidized insulin B chain are Phel, His5 and Arg22, which lead to the selective cleavages of the peptide bonds at Phe1-Val2, His5-Leu6, Glu21-Arg22, and Arg22-Gly23 of oxidized insulin B chain.展开更多
An unsymmetrical oxovanadium complex [VO(SAA)(phen) ](1),(SAA = salicylidene anthranilic acid,phen = phenanthroline) and its novel derivatives [VO(MOSAA)(phen) ](2)(MOSAA = 2-hydroxy-4-methoxysalicylidene anthranilic)...An unsymmetrical oxovanadium complex [VO(SAA)(phen) ](1),(SAA = salicylidene anthranilic acid,phen = phenanthroline) and its novel derivatives [VO(MOSAA)(phen) ](2)(MOSAA = 2-hydroxy-4-methoxysalicylidene anthranilic) have been synthesized and characterized by elemental analysis,UV-Vis,ES-MS,IR and 1 H NMR.The interaction of these two complexes with CT-DNA was investigated by absorption titration,fluorescence spectra,viscosity measurements and thermal denaturation.Their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated by gel electrophoresis experiments.The cytotoxicity of these two complexes against Myeloma cell(Ag8.653) and Gliomas cell(U251) have been assessed by MTT assay.The experimental results show that both complexes 1 and 2 bind to CT-DNA in classical intercalation mode,and the DNA-binding affinity of the complex 1 is larger than that of complex 2.It is interesting to note that these two complexes prominently enhance the oxidative cleavage of supercoiled pBR322 DNA and both complexes present cytotoxic activities against Ag8.653 and U251 cell lines.Complex 1 possessed the more potent inhibitory effect against the two cell lines of the two complexes.展开更多
Three mononuclear oxovanadium complexes [VO(Hbid)(CF3PIP)] (1) (Hbid=(E)-2-(2-hydroxybenzylideneamino) isoindoline-1,3-dione, CF3PIP=2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10] phenanthroline), [VO(Hbid)(m-CF3P...Three mononuclear oxovanadium complexes [VO(Hbid)(CF3PIP)] (1) (Hbid=(E)-2-(2-hydroxybenzylideneamino) isoindoline-1,3-dione, CF3PIP=2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10] phenanthroline), [VO(Hbid)(m-CF3PIP)];(2) (m-CF3PIP=2-(3-trifluoromethyl phenyl)imidazole [4, 5-f][1,10]phenanthroline) and [VO(Hbid)(p-CF3PIP)];(3) (p-CF3PIP=2-(4-trifluoromethyl phenyl) imidazole[4,5-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis, IR, molar conductance, ES-MS and 1H NMR. The DNA-binding properties of these complexes were studied by using UV-Vis absorption titration, fluorescence spectra, viscosity measurements and thermal denaturation studies. The results show that 1, 2 and 3 interact with calf thymus DNA (CT-DNA) by intercalation modes and the magnitude of their intrinsic binding constants (Kb values) follows the order: 2 < 1 < 3. Furthermore, their photocleavage properties with pBR322 plasmid DNA were investigated by agarose gel electrophoresis experiments. The DNA cleavage capacity of complex 3 is also stronger than that of 1 and 2.展开更多
BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore ...BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.展开更多
Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face in...Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.展开更多
A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,...A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
Chloride ions(Cl^(-))have been shown to impact the long-lasting nature of reinforced concrete.However,Cl^(-)that are already bound inside the concrete will not lead to the deterioration of the concrete’s characterist...Chloride ions(Cl^(-))have been shown to impact the long-lasting nature of reinforced concrete.However,Cl^(-)that are already bound inside the concrete will not lead to the deterioration of the concrete’s characteristics.The composition of the cement-based material,including the type of cement and auxiliary materials,greatly influences the ability of the material to bind Cl^(-),and varied components result in varying binding beha-vior of the Cl^(-).Simultaneously,the Cl^(-)binding process in concrete is influenced by both the internal and exterior surroundings,as well as the curing practices.These factors impact the hydration process of the cement and the internal pore structure of the concrete.Currently,mathematical theories and molecular dynamics simulations have increasingly been employed as the prevalent methods for examining the binding behaviors of Cl^(-)in concrete.These techniques are extensively utilized for predicting the lifespan and conducting microscopic studies of reinforced concrete in Cl^(-)settings.This work proposes recommendations for future research based on a summary of experimental and simulation investigations on Cl^(-)binding.Which will offer theoretical guidance for studying the binding of Cl^(-)in cement-based materials.展开更多
While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms...While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms to produce diversity,including class switch recombination(CSR),subclass differentiation,and alternative expression of the same gene.Many species of birds,reptiles,and amphibians express a truncated isoform of immunoglobulin Y(IgY),termed IgY(ΔFc),which lacks theυCH3 andυCH4 domains.In Anseriformes,IgY(ΔFc)arises from alternative transcriptional termination sites within the sameυgene,whereas in some turtles,intact IgY and IgY(ΔFc)are encoded by distinct genes.Different from the previously reported IgY(ΔFc)variants,this study identified a truncated IgY in the snake Elaphe taeniura,characterized by the loss of only a portion of the CH4 domain.Western blotting and liquid chromatographytandem mass spectrometry confirmed that this truncated IgY is generated by post-translational cleavage at N338 within the IgY heavy chain constant(CH)region.Furthermore,both human and snake asparaginyl endopeptidase were shown to cleave snake IgY in vitro.These findings reveal a novel mechanism for the production of shortened IgY forms,demonstrating that the immunoglobulin CH region undergoes diversification through distinct strategies across vertebrates.展开更多
The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studie...The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studies focus on designing homogeneous or noble metal catalysts and conducting the reactions under basic conditions.Here,we report an efficient process for the C-C bond cleavage of lignin model compounds and selectively producing esters over different shaped CeO_(2)(i.e.,nanospheres(S),nanorods(R),nanoparticles(P),and nanocubes(C))under base-free conditions.Specifically,the yield of methyl anisate from the aerobic oxidation of l-(4-methoxyphenyl)ethanol reaches 77.6%over CeO_(2)-S in one hour(91%in 9 h),exhibiting higher performance compared to other evaluated CeO_(2)catalysts(6.4%-40.2%).Extensivecharacterizations and experimental investigations reveal that the density of weak base sites and oxygen vacancies on the CeO_(2)surface is positively correlated with the yield of methyl esters.Furthermore,the reaction pathway is investigated,which confirms that 1-(4-methoxyphenyl)ethanol first undergoes two reactions(i.e.,etherification and dehydrogenation)to produce intermediates of1-methoxy-4-(1-methoxy-ethyl)-benzene and 1-(4-methoxyphenyl)ethanone,respectively,followed by a series of functional group transformations to generate the targeted methyl anisate ultimately.展开更多
Elucidation of ligand-protein interactions provides new insights into the physiological functions and mechanisms of ligand molecules,enabling new ideas for the treatment of diseases,and drug discovery and development....Elucidation of ligand-protein interactions provides new insights into the physiological functions and mechanisms of ligand molecules,enabling new ideas for the treatment of diseases,and drug discovery and development.Most ligand-protein binding occurs only in specific regions of proteins.The identification of protein targets and binding regions is crucial for drug discovery and development,as well as for the in-depth study of drug-protein conformational relationships[1].展开更多
The efficient conversion of lignin into mono-cycloalkanes via both C–O and C–C bonds cleavage are attractive,but challenging due to the high C–C bond dissociation energy.Previous studies have demonstrated that NbO_...The efficient conversion of lignin into mono-cycloalkanes via both C–O and C–C bonds cleavage are attractive,but challenging due to the high C–C bond dissociation energy.Previous studies have demonstrated that NbO_(x)-based catalysts exhibited exceptional capabilities for C_(Ar)–C bond cleavage and broken the limitation of lignin monomers.In this work,we presented an economical multifunctional Pt-Nb/MOR catalyst that achieved an impressive monomer yield of 147%during the depolymerization and hydrodeoxygenation of lignin into mono-cycloalkanes.Reaction pathway studies showed that unlike traditional NbO_(x)-based catalytic system,bicyclohexane was an important intermediate in this system and followed the C_(sp3)–C_(sp3)cleavage pathway after complete cyclic-hydrogenation.Deep investigations demonstrated that the doping of Nb in Pt/MOR not only enhanced the activation of hydrogen by Pt,but also increased the acidity of MOR,both of these are favor for the hydrogenolytic cleavage of C_(sp3)–C_(sp3)bonds.This work provides a low-cost catalyst to obtain high-yield monomers from lignin under relatively mild conditions and would help to design catalysts with higher activity for the valorization of lignin.展开更多
基金the National Natural Science Foundation of China (Nos.21105091 and 20772113) for the financial support
文摘A series of novel pyrazole fused heterocyclic derivatives were synthesized via a two-step procedure or a one-pot two step method, and their catalytic DNA cleavage abilities and anti-BVDV activities were also evaluated. The results obtained indicated that compounds 3b-3c could catalyze the cleavage of supercoiled DNA （pUC 19 plasmid DNA） to nicked DNA under physiological conditions with high yields via a hydrolytic mechanism. The studies on anti-viral activities against bovine viral diarrhea virus （BVDV） demonstrated that some of the pyrazole derivatives showed pronounced anti-BVDV activity with interesting ECso values and no significant cytotoxicity. Among them, compound 31 showed the highest antiviral activity （ECso = 0.12 μmol/L） and was 10 fold more than that of the positive control ribavirin （ECso = 1.3 μmol/L）, which provided a potential candidate for the development of anti-BVDV agents.
基金financial support from the National Key R&D Program of China (No.2021YFA1302604)Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021B017)China Postdoctoral Science Foundation (No.2023T160727)。
文摘RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.
基金supported by the National Natural Science Foundation of China (52172228)the Natural Science Foundation of Fujian Province (2024J01475 and 2023J05127)
文摘Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.
基金Project(21001118)supported by National Natural Science Foundation of ChinaProject(12JJ3016)supported by Natural Science Foundation of Hunan Province,China
文摘A copper-bispyridylpyrrolide complex [Cu(PDPH)Cl](PDPH = 2,5-bis(2′-pyridyl)pyrrole) was synthesized and characterized. The complex crystallizes in the orthorhombic system with space group Pccn, a = 0.9016(3) nm, b = 1.0931(4) nm, c =2.5319(8) nm, and V = 2.4951(15) nm3. The copper center is situated in a square planar geometry. The interaction of the copper(II)complex with calf thymus DNA(CT-DNA) was investigated by electronic absorption, circular dichroism(CD) and fluorescence spectra. It is proposed that the complex binds to CT-DNA through groove binding mode. Nuclease activity of the complex was also studied by gel electrophoresis method. The complex can efficiently cleave supercoiled p BR322 DNA in the presence of ascorbate(H2A) via oxidative pathway. The preliminary mechanism of DNA cleavage by the complex with different inhibiting reagents indicates that the hydroxyl radicals were involved as the active species in the DNA cleavage process.
基金Natural Science Foundation of Liaoning Province, China(No.20061073)Education Committee Foundation of Liaoning Province, China(No.22004F023)
文摘A new dinuclear complex, [Ag（L）（CH3CN）]2（ClO4）2·2H2O（L=2,3-di-2-pyridylquinoxaline）, was prepared and characterized by elemental analyses, IR spectroscopy, and single-crystal X-ray diffraction analyses. The interaction of the complex with calf thymus DNA（CT-DNA） was investigated by absorption, fluorescence spectroscopies, and viscosity measurement. The results suggested that the complex was bound to DNA via an intercalative mode. The intrinsic binding constant value Kb was found to be approximately 1.48×10^3 L·mol^-1. Moreover, the Ag（I） complex could cleave the plasmid pUC19 DNA from the supercoiled Form Ⅰto the nicked FormⅡ under irradiation at 365 nm.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB29050100)the National Key Research and Development Program of China (Grant No.2022YFC0869900,2022YFC2303501,2020YFC0861100)the Program of the Chinese Academy of Sciences (Grant No.2020YJFK-Z-0150).
文摘SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted comparisons.Here,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the wild-type.In addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to hACE2.We also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host cells.Furthermore,all variants'pseudoviruses we tested gained the ability to enter the animal ACE2-expressing cells.Especially the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral evolution.The insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.
基金support from the National Natural Science Foundation of China(No.20132020)the National Science and Technology Committee of China,Chinese National Ministry of Education and Tsinghua University
文摘We reported the synthesis of a simple bifunctional molecule and the interaction between this molecule and DNA were studied by UV and the DNA cleavage behavoior was determined by agarose gel electrophoresis.
文摘The electrospray ionization mass spectrometry investigation showed that the binding sites of [ZnL]^2＋, where L is 2-[bis（2- aminoethyl）amino]ethanol, with oxidized insulin B chain are Phel, His5 and Arg22, which lead to the selective cleavages of the peptide bonds at Phe1-Val2, His5-Leu6, Glu21-Arg22, and Arg22-Gly23 of oxidized insulin B chain.
文摘An unsymmetrical oxovanadium complex [VO(SAA)(phen) ](1),(SAA = salicylidene anthranilic acid,phen = phenanthroline) and its novel derivatives [VO(MOSAA)(phen) ](2)(MOSAA = 2-hydroxy-4-methoxysalicylidene anthranilic) have been synthesized and characterized by elemental analysis,UV-Vis,ES-MS,IR and 1 H NMR.The interaction of these two complexes with CT-DNA was investigated by absorption titration,fluorescence spectra,viscosity measurements and thermal denaturation.Their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated by gel electrophoresis experiments.The cytotoxicity of these two complexes against Myeloma cell(Ag8.653) and Gliomas cell(U251) have been assessed by MTT assay.The experimental results show that both complexes 1 and 2 bind to CT-DNA in classical intercalation mode,and the DNA-binding affinity of the complex 1 is larger than that of complex 2.It is interesting to note that these two complexes prominently enhance the oxidative cleavage of supercoiled pBR322 DNA and both complexes present cytotoxic activities against Ag8.653 and U251 cell lines.Complex 1 possessed the more potent inhibitory effect against the two cell lines of the two complexes.
文摘Three mononuclear oxovanadium complexes [VO(Hbid)(CF3PIP)] (1) (Hbid=(E)-2-(2-hydroxybenzylideneamino) isoindoline-1,3-dione, CF3PIP=2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10] phenanthroline), [VO(Hbid)(m-CF3PIP)];(2) (m-CF3PIP=2-(3-trifluoromethyl phenyl)imidazole [4, 5-f][1,10]phenanthroline) and [VO(Hbid)(p-CF3PIP)];(3) (p-CF3PIP=2-(4-trifluoromethyl phenyl) imidazole[4,5-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis, IR, molar conductance, ES-MS and 1H NMR. The DNA-binding properties of these complexes were studied by using UV-Vis absorption titration, fluorescence spectra, viscosity measurements and thermal denaturation studies. The results show that 1, 2 and 3 interact with calf thymus DNA (CT-DNA) by intercalation modes and the magnitude of their intrinsic binding constants (Kb values) follows the order: 2 < 1 < 3. Furthermore, their photocleavage properties with pBR322 plasmid DNA were investigated by agarose gel electrophoresis experiments. The DNA cleavage capacity of complex 3 is also stronger than that of 1 and 2.
基金Supported by the Talent Launch Fund of Chongqing Medical University Affiliated University City HospitalChongqing Medical University Affiliated University City Hospital Youth Program,No.2021ZD05.
文摘BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.
基金financially supported by the Green Development and Demonstration Programme(GUDP)(case number 34009-19-1585)。
文摘Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.
基金supported by the National Natural Science Foundation of China(32273037 and 32102636)the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007)+4 种基金Laboratory of Lingnan Modern Agriculture Project(NT2021007)the Guangdong Science and Technology Innovation Leading Talent Program(2019TX05N098)the 111 Center(D20008)the double first-class discipline promotion project(2023B10564003)the Department of Education of Guangdong Province(2019KZDXM004 and 2019KCXTD001).
文摘A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
文摘Chloride ions(Cl^(-))have been shown to impact the long-lasting nature of reinforced concrete.However,Cl^(-)that are already bound inside the concrete will not lead to the deterioration of the concrete’s characteristics.The composition of the cement-based material,including the type of cement and auxiliary materials,greatly influences the ability of the material to bind Cl^(-),and varied components result in varying binding beha-vior of the Cl^(-).Simultaneously,the Cl^(-)binding process in concrete is influenced by both the internal and exterior surroundings,as well as the curing practices.These factors impact the hydration process of the cement and the internal pore structure of the concrete.Currently,mathematical theories and molecular dynamics simulations have increasingly been employed as the prevalent methods for examining the binding behaviors of Cl^(-)in concrete.These techniques are extensively utilized for predicting the lifespan and conducting microscopic studies of reinforced concrete in Cl^(-)settings.This work proposes recommendations for future research based on a summary of experimental and simulation investigations on Cl^(-)binding.Which will offer theoretical guidance for studying the binding of Cl^(-)in cement-based materials.
基金supported by the Fundamental Research Funds for the Central Universities,Southwest Minzu University(ZYN2023097)Scientific and Technological Innovation Team for Qinghai-Xizang Plateau Research in Southwest Minzu University(2024CXTD13)。
文摘While variable regions of immunoglobulins are extensively diversified by V(D)J recombination and somatic hypermutation in vertebrates,the constant regions of immunoglobulin heavy chains also utilize certain mechanisms to produce diversity,including class switch recombination(CSR),subclass differentiation,and alternative expression of the same gene.Many species of birds,reptiles,and amphibians express a truncated isoform of immunoglobulin Y(IgY),termed IgY(ΔFc),which lacks theυCH3 andυCH4 domains.In Anseriformes,IgY(ΔFc)arises from alternative transcriptional termination sites within the sameυgene,whereas in some turtles,intact IgY and IgY(ΔFc)are encoded by distinct genes.Different from the previously reported IgY(ΔFc)variants,this study identified a truncated IgY in the snake Elaphe taeniura,characterized by the loss of only a portion of the CH4 domain.Western blotting and liquid chromatographytandem mass spectrometry confirmed that this truncated IgY is generated by post-translational cleavage at N338 within the IgY heavy chain constant(CH)region.Furthermore,both human and snake asparaginyl endopeptidase were shown to cleave snake IgY in vitro.These findings reveal a novel mechanism for the production of shortened IgY forms,demonstrating that the immunoglobulin CH region undergoes diversification through distinct strategies across vertebrates.
基金financially supported by the National Key Research and Development Program of China(No.2023YFD2200505)the National Natural Science Foundation of China(No.22202105)+3 种基金the Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.21KJA150003)the Innovation and Entrepreneurship Team Program of Jiangsu Province(No.JSSCTD202345)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_1163)the China Postdoctoral Science Foundation(Nos.2023M731703 and 2024T170415)
文摘The oxidation of lignin model compounds to esters via C-C bond cleavage has attracted considerable attention,as esters could be used as important polymer precursors and pharmaceutical intermediates.However,most studies focus on designing homogeneous or noble metal catalysts and conducting the reactions under basic conditions.Here,we report an efficient process for the C-C bond cleavage of lignin model compounds and selectively producing esters over different shaped CeO_(2)(i.e.,nanospheres(S),nanorods(R),nanoparticles(P),and nanocubes(C))under base-free conditions.Specifically,the yield of methyl anisate from the aerobic oxidation of l-(4-methoxyphenyl)ethanol reaches 77.6%over CeO_(2)-S in one hour(91%in 9 h),exhibiting higher performance compared to other evaluated CeO_(2)catalysts(6.4%-40.2%).Extensivecharacterizations and experimental investigations reveal that the density of weak base sites and oxygen vacancies on the CeO_(2)surface is positively correlated with the yield of methyl esters.Furthermore,the reaction pathway is investigated,which confirms that 1-(4-methoxyphenyl)ethanol first undergoes two reactions(i.e.,etherification and dehydrogenation)to produce intermediates of1-methoxy-4-(1-methoxy-ethyl)-benzene and 1-(4-methoxyphenyl)ethanone,respectively,followed by a series of functional group transformations to generate the targeted methyl anisate ultimately.
文摘Elucidation of ligand-protein interactions provides new insights into the physiological functions and mechanisms of ligand molecules,enabling new ideas for the treatment of diseases,and drug discovery and development.Most ligand-protein binding occurs only in specific regions of proteins.The identification of protein targets and binding regions is crucial for drug discovery and development,as well as for the in-depth study of drug-protein conformational relationships[1].
文摘The efficient conversion of lignin into mono-cycloalkanes via both C–O and C–C bonds cleavage are attractive,but challenging due to the high C–C bond dissociation energy.Previous studies have demonstrated that NbO_(x)-based catalysts exhibited exceptional capabilities for C_(Ar)–C bond cleavage and broken the limitation of lignin monomers.In this work,we presented an economical multifunctional Pt-Nb/MOR catalyst that achieved an impressive monomer yield of 147%during the depolymerization and hydrodeoxygenation of lignin into mono-cycloalkanes.Reaction pathway studies showed that unlike traditional NbO_(x)-based catalytic system,bicyclohexane was an important intermediate in this system and followed the C_(sp3)–C_(sp3)cleavage pathway after complete cyclic-hydrogenation.Deep investigations demonstrated that the doping of Nb in Pt/MOR not only enhanced the activation of hydrogen by Pt,but also increased the acidity of MOR,both of these are favor for the hydrogenolytic cleavage of C_(sp3)–C_(sp3)bonds.This work provides a low-cost catalyst to obtain high-yield monomers from lignin under relatively mild conditions and would help to design catalysts with higher activity for the valorization of lignin.
