Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total ...Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.展开更多
Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to ...Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to the normal population.Thus,novel treatment approaches are required to reduce depressive symptoms among diabetic individuals.Traditional Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient time.Methods:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats.The antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])analysis.Results:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the study.Treatment with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel environment.Treatment with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in depression.Conclusion:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.展开更多
Discharge plasmas, recognized as unique platforms for investigating the origins of chemical life, have garnered extensive interest for their potential to simulate prebiotic conditions. This paper embarks on a comprehe...Discharge plasmas, recognized as unique platforms for investigating the origins of chemical life, have garnered extensive interest for their potential to simulate prebiotic conditions. This paper embarks on a comprehensive overview of recent advancements in the plasma-enabled synthesis of life’s building blocks, charting the complex environmental parameters believed to have surrounded life’s inception. This discussion elaborates on the fundamental mechanisms of discharge plasmas and their likely role in fostering conditions necessary for the origin of life on early Earth. We consider a variety of chemical reactions facilitated by plasma, specifically the synthesis of vital organic molecules - amino acids, nucleobases, sugars, and lipids. Further, we delve into the impact of plasmas on prebiotic chemical evolution. We expect this review to open new horizons for future investigations in plasma-related prebiotic chemistry that could offer valuable insights for unraveling the mysteries of life's origin.展开更多
The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma.The synthesis of abiotic peptides from amino acids(AAs)is primarily constrained by high activation energies and unfavorable t...The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma.The synthesis of abiotic peptides from amino acids(AAs)is primarily constrained by high activation energies and unfavorable thermodynamics,necessitating the identification of plausible prebiotic alternatives for synthesizing prebiotic peptides.Here we present a plausible pathway to the formation of prebiotic peptides,wherein oligopeptides,oligopeptide amides,and cyclic oligopeptides can be directly synthesized from amino acid amides(AA-NH2)under wet–dry cycle conditions without the need for any enhancers.The subsequent investigation revealed that AA-NH2 demonstrated more favorable thermodynamic reaction effects than AAs in peptide formation.In contrast to the polymerization of AAs,the process of peptide formation through the polymerization of AA-NH2 was significantly simplified.Additionally,AA-NH2 was discovered to function as a“bridge”for the formation of peptides from AAs,thereby facilitating their participation in the synthesis of intricate peptide structures.On the basis of these findings,a plausible mechanism for the prebiotic origin network of peptides under primordial Earth conditions has been proposed.Overall,this research presents a plausible pathway for the generation of prebiotic peptides and peptide libraries within prebiotic environments.展开更多
The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that t...The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions,2 salt bridges,5 conventional hydrogen bond interactions,and 4 attractive charge interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.展开更多
Diffusion-ordered nuclear magnetic resonance spectroscopy(DOSY),dubbed chromato-graphic NMR spectroscopy,can be used to simultaneously distinguish and identify the structures of components in a mixture according to th...Diffusion-ordered nuclear magnetic resonance spectroscopy(DOSY),dubbed chromato-graphic NMR spectroscopy,can be used to simultaneously distinguish and identify the structures of components in a mixture according to their different diffusion coefficients.In order to improve the resolution of DOSY on the diffusion dimension,a lot of matrices have been developed to expand the application of this technique in mixture analysis.However,there is no matrix to detect the mixture of ionic liquids(ILs).Herein,we introduced a new matrix,poly(sodium-p-styrenesulfonate)(PSSNa),which can be used to fully separate the signals of a mixture of different ILs.The mixture of three imidazolium ILs of 1-butyl-3-methylimidazolium bromide,1-allyl-3-vinylimidazolium bromide and 1-arboxymethy-3-methylimidazolium chloride could be fully distinguished by virtue of their different interactions with PSSNa.We also investigated the influences of PSSNa amount,IL con-centration and solution pH value on the signal resolution of mixtures.This work provides a scientific reference for the analysis of the other IL analytes.展开更多
The development of Chinese space science and technology plays a great role in promoting the researches in the field of the origin of life.With the multidisciplinary cooperation,there are fruitful achievements in this ...The development of Chinese space science and technology plays a great role in promoting the researches in the field of the origin of life.With the multidisciplinary cooperation,there are fruitful achievements in this research field obtained over the past two years.This report summarizes the major progress of the basic researches about the origin of life in China during 2018–2020.展开更多
The divergent behavior of C-H bond oxidations of aliphatic substrates compared to those of aromatic substrates shown in Gupta’s experiment was mechanistically studied herein by means of density functional theory calc...The divergent behavior of C-H bond oxidations of aliphatic substrates compared to those of aromatic substrates shown in Gupta’s experiment was mechanistically studied herein by means of density functional theory calculations.Our calculations reveal that such difference is caused by different reaction mechanisms between two kinds of substrates(the aliphatic cyclohexane,2,3-dimethylbutane and the aromatic toluene,ethylbenzene and cumene).For the aliphatic substrates,C-H oxidation by the oxidant Fe^(V)(O)(TAML)is a hydrogen atom transfer process;whereas for the aromatic substrates,C-H oxidation is a proton-coupled electron transfer(PCET)process with a proton transfer character on the transition state,that is,a proton-coupled electron transfer process holding a proton transfer-like transition state(PCET(PT)).This difference is caused by the strongπ-πinteractions between the tetra-anionic TAML ring and the phenyl ring of the aromatic substrates,which has a“pull”effect to make the electron transfer from substrates to the Fe=O moiety inefficient.展开更多
In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the periph...In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.展开更多
The interaction between the aggregation-induced emissive(AIE) luminogens(AIEgen) and the polymer is the key scientific question in the design of functional AIE hydrogels. In this study, we report the AIE behavior of a...The interaction between the aggregation-induced emissive(AIE) luminogens(AIEgen) and the polymer is the key scientific question in the design of functional AIE hydrogels. In this study, we report the AIE behavior of a poly(acrylic acid)(PAAc) and poly(acrylamide)(PAAm) interpenetrating network(IPN) hydrogel doped with tetra-cationic tetraphenylethene(TCTPE). The cationic AIEgen can bind with PAAc through ionic interaction, while PAAc and PAAm chains can associate with each other through hydrogen-bonds(H-bonds). These two interactions can restrict the intramolecular rotation and thus activate the luminescence of the AIEgen. The PAAc-PAAm H-bonds can be broken by increasing temperature or p H, restoring the intramolecular rotation of the AIEgen and quenching the fluorescence of the hydrogel. Therefore, the TCTPE-doped IPN hydrogel is designed as temperature-and p H-sensitive displayers which can record information imprinted by photo-printing or iono-printing with good switchability and reversibility. Another application of this TCTPE-doped hydrogel is demonstrated as a luminescent soft actuator, which has fast shape deformation and editable fluorescence pattern. The above results reveal a pathway to tune the emission behavior through tuning polymer-polymer and polymer-AIEgen interactions, which may inspire new design strategies of aggregation-induced emissive polymers and broaden their applications.展开更多
Prebiotic peptide synthesis is a central issue concerning life's origins. Many studies considered that life might come from Hadean deep-sea environment, that is, under high hydrostatic pressure conditions.However,...Prebiotic peptide synthesis is a central issue concerning life's origins. Many studies considered that life might come from Hadean deep-sea environment, that is, under high hydrostatic pressure conditions.However, the properties of prebiotic peptide formation under high hydrostatic pressure conditions have seldom been mentioned. Here we report that the yields of dipeptides increase with raised pressures.Significantly, effect of pressure on the formation of dipeptide was obvious at relatively low temperature.Considering that the deep sea is of high hydrostatic pressure, the pressure may serve as one of the key factors in prebiotic peptide synthesis in the Hadean deep-sea environment. The high hydrostatic pressure should be considered as one of the significant factors in studying the origin of life.展开更多
A CuX-mediated regioselective halogenation reaction of 2-phenylimidazo[1,2-a]pyridine in the presence of oxygen is introduced in this paper.This reaction provides an effective method for the production of C-3 halogena...A CuX-mediated regioselective halogenation reaction of 2-phenylimidazo[1,2-a]pyridine in the presence of oxygen is introduced in this paper.This reaction provides an effective method for the production of C-3 halogenated 2-phenylimidazo[1,2-a]pyridines with a yield of up to 96%.A plausible mechanism for the formation of title compounds via 2-phenylimidazo[1,2-a]pyridine–CuX complex intermediate is proposed.The structure of representative compounds is established by the single crystal XRD method.The electronic structure,corroborated by Hirshfeld surface analysis and DFT calculations,rationalizes characters of relevant absorptions and emission as well as large Stokes shifts.展开更多
The enantioselective epoxidation of olefin by Mn^(II)(R,R-PMCP)(OTf)2, H_(2)O_(2) and H_(2)SO_(4) was explored by DFT calculations and experiments. Theoretical results suggest that [Mn^(V)(O)(R,R-PMCP)(SO_(4))]^(+) sp...The enantioselective epoxidation of olefin by Mn^(II)(R,R-PMCP)(OTf)2, H_(2)O_(2) and H_(2)SO_(4) was explored by DFT calculations and experiments. Theoretical results suggest that [Mn^(V)(O)(R,R-PMCP)(SO_(4))]^(+) species with a triplet ground spin state serves as the active species for the olefin epoxidation. It can be generated by the H_(2)SO_(4) assisted O-O heterolysis of Mn^(III)(OOH) species. Mn^(III)-persulfate is also involved in this system, but it cannot promote the olefin epoxidation directly, preferring instead to transform into Mn^(V)(O). Actually, the asymmetric epoxidation reactions with H_(2)O_(2)/H_(2)SO_(4) or Oxone provide similar enantioselectivity in the presence of manganese catalyst. These observations further support the transformation of Mn^(III)-persulfate to Mn^(V)(O) species.展开更多
Prebiotic peptide synthesis and the origin of the genetic code are central issues concerning the origin of life.The question of how they are possibly correlated on the primordial Earth remains perplexing,although nume...Prebiotic peptide synthesis and the origin of the genetic code are central issues concerning the origin of life.The question of how they are possibly correlated on the primordial Earth remains perplexing,although numerous experiments have been carried out to explain the prebiotic chemistry of peptide synthesis and the genetic code origin.The purpose of this article is to review the chemical reactions occurred during the synthesis of peptides and the origin of the genetic code in the early Earth aqueous environment.Meanwhile,we attempt to review their relationship as well.At last,from our perspective,the chiral properties of biomolecules should be taken into account in the prebiotic chemical scenarios,which may contribute to some breakthroughs in the further research of this field.展开更多
Riptortus pedestris(Fabricius),one of the major piercing-sucking insects in soybeans,causes delayed plant senescence and abnormal pods,known as staygreen syndrome.Recent research has shown that direct feeding of this ...Riptortus pedestris(Fabricius),one of the major piercing-sucking insects in soybeans,causes delayed plant senescence and abnormal pods,known as staygreen syndrome.Recent research has shown that direct feeding of this insect is the major cause of soybean staygreen syndrome.However,it remains unclear whether R.pedestris salivary proteins play vital roles in insect infestation.Here,we found that 4 secretory salivary proteins can induce cell death in Nicotiana benthamiana by transient heterologous expression.The cell death induced by Rp2155 relies on the nucleotide-binding leucine-rich repeat helper,HSP90.Tissue-specificity assays indicated that Rp2155 is specifically expressed in the salivary gland of R.pedestris and is significantly induced during insect feeding.The expression of salicylic acid(SA)-,jasmonic acid(JA)-related genes was increased in soybean when fed by Rp2155-silenced R.pedestris.More importantly,soybean staygreen symptoms caused by R.pedestris were significantly alleviated when Rp2155 was silenced.Together,these results suggest that the salivary effector Rp2155 is involved in promoting insect infestation by suppressing the JA and SA pathways,and it can be considered as a potential RNA interference target for insect control.展开更多
Amyloid proteins correlate with a series of degenerative diseases. Targeting amyloid aggregation has remained a hot topic in therapeutic studies. Numerous inhibitors have been developed, but very few have been approve...Amyloid proteins correlate with a series of degenerative diseases. Targeting amyloid aggregation has remained a hot topic in therapeutic studies. Numerous inhibitors have been developed, but very few have been approved for marketing. Meanwhile, the growing knowledge of amyloid structural characteristics provides a basis for the rational design of inhibitors. Here we introduce the high-resolution structural findings of amyloid fibrils in recent years and discuss the reported strategies toward rationally designed inhibitors based on amyloid-related structural studies.展开更多
Protein N-phosphorylation is widely present in nature and participates in various biological processes.However,current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation.In this ...Protein N-phosphorylation is widely present in nature and participates in various biological processes.However,current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation.In this study,we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein N-phosphorylation.Upon these substantial data,we characterized the sequential and structural features of protein N-phosphorylation.Moreover,after comparing hundreds of learning models,we chose and optimized gradient boosting decision tree(GBDT)models to predict three types of human N-phosphorylation,achieving mean area under the receiver operating characteristic curve(AUC)values of 90.56%,91.24%,and 92.01%for pHis,pLys,and pArg,respectively.Meanwhile,we discovered 488,825 distinct N-phosphosites in the human proteome.The models were also deployed in Nphos for interactive N-phosphosite prediction.In summary,this work provides new insights and points for both flexible and focused investigations of N-phosphorylation.It will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical foundation.Nphos is freely available at http://www.bio-add.org/Nphos/and http://ppodd.org.cn/Nphos/.展开更多
Arginine phosphorylation(p Arg)is recently discovered as a ubiquitous protein N-phosphorylation in bacteria.However,its prevalence and roles in mammalian cells remain largely unknown due to the lack of established wor...Arginine phosphorylation(p Arg)is recently discovered as a ubiquitous protein N-phosphorylation in bacteria.However,its prevalence and roles in mammalian cells remain largely unknown due to the lack of established workflow and the inherent lability of phosphoramidate(P–N)bond.Emerging evidences suggest that N-phosphorylation may extensively exist in eukaryotes and play crucial roles.We report a phosphoproteomic workflow,which allows for the first time revealing the widespread occurrence of p Arg in human cells by mass spectrometry.By virtue of this approach,we identified 152 high-confidence p Arg sites derived from 118 proteins.Remarkably,the discovered p Arg phosphorylation motif and gene ontology hint a possible cellular function of arginine phosphorylation which may regulate the favorability of propeptide convertase substrate.The obtained p Arg dataset paves a way for a better understanding of the biological functions of eukaryotic p Arg in the future.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control ...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus.This has led to a great demand for easy preparation and scalable vaccines,especially in low-income countries.Here,we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein.The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs,which might be capable of protecting the host from infection without systemic toxicity.In addition,the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2.Furthermore,inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection.This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.展开更多
of main observation and conclusion RET G-quadruplex DNA(G4-DNA)is formed in the promoter region of RET protein,which is involved in the initiation and progression of human cancers.Berberine inhibits cancer cell growth...of main observation and conclusion RET G-quadruplex DNA(G4-DNA)is formed in the promoter region of RET protein,which is involved in the initiation and progression of human cancers.Berberine inhibits cancer cell growth through interactions with RET G4-DNA,but how it binds to RET G4-DNA remains unknown.Previously,we reported that colchicine selectively bound to RET G4-DNA,but the structural basis of its binding selectivity is still unclear.Here,mainly by NMR,we demonstrated how berberine bound to RET G4-DNA in a means different from colchicine,and implied several key determinants for small molecules specifically binding to one G4-DNA.展开更多
基金International Cooperative Project of Traditional Chinese Medicine(GZYYG2020023)CAMS Innovation Fund for Medical Sciences(CIFMS)Grant(2021-I2M-1-034)Key Research Project of Hunan Province(222SK2018).
文摘Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.
基金We thank the National High-End Foreign Experts Recruitment Plan(G2022051012L)National Key Research and Development Program of China(2016YFE0131800)+1 种基金Science and Technology Department of Sichuan Province(2019YFH0023)the High-End Talents Recruitment Program(Liu Xinmin group)of Luzhou Municipal People's Government.
文摘Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to the normal population.Thus,novel treatment approaches are required to reduce depressive symptoms among diabetic individuals.Traditional Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient time.Methods:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats.The antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])analysis.Results:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the study.Treatment with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel environment.Treatment with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in depression.Conclusion:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.
基金National Natural Science Foundation of China General Project(52377160)National Natural Science Foundation of China National Young Talents Project(GYKP010)+1 种基金Shaanxi Provincial Natural Science Program(2023-JC-YB-425)Xi′an Jiaotong University Young Top Talents Program.
文摘Discharge plasmas, recognized as unique platforms for investigating the origins of chemical life, have garnered extensive interest for their potential to simulate prebiotic conditions. This paper embarks on a comprehensive overview of recent advancements in the plasma-enabled synthesis of life’s building blocks, charting the complex environmental parameters believed to have surrounded life’s inception. This discussion elaborates on the fundamental mechanisms of discharge plasmas and their likely role in fostering conditions necessary for the origin of life on early Earth. We consider a variety of chemical reactions facilitated by plasma, specifically the synthesis of vital organic molecules - amino acids, nucleobases, sugars, and lipids. Further, we delve into the impact of plasmas on prebiotic chemical evolution. We expect this review to open new horizons for future investigations in plasma-related prebiotic chemistry that could offer valuable insights for unraveling the mysteries of life's origin.
基金National Natural Science Foundation of China(Nos.42388101,92256203,and 42003062)Fundamental Research Funds for the Provincial Universities of Zhejiang(No.SJLY2023007)+1 种基金Technology and Engineering Center for Space Utilization,Chinese Academy of Sciences(No.YYWT-0901-EXP-16)Ningbo Top Talent Project(No.215-432094250).
文摘The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma.The synthesis of abiotic peptides from amino acids(AAs)is primarily constrained by high activation energies and unfavorable thermodynamics,necessitating the identification of plausible prebiotic alternatives for synthesizing prebiotic peptides.Here we present a plausible pathway to the formation of prebiotic peptides,wherein oligopeptides,oligopeptide amides,and cyclic oligopeptides can be directly synthesized from amino acid amides(AA-NH2)under wet–dry cycle conditions without the need for any enhancers.The subsequent investigation revealed that AA-NH2 demonstrated more favorable thermodynamic reaction effects than AAs in peptide formation.In contrast to the polymerization of AAs,the process of peptide formation through the polymerization of AA-NH2 was significantly simplified.Additionally,AA-NH2 was discovered to function as a“bridge”for the formation of peptides from AAs,thereby facilitating their participation in the synthesis of intricate peptide structures.On the basis of these findings,a plausible mechanism for the prebiotic origin network of peptides under primordial Earth conditions has been proposed.Overall,this research presents a plausible pathway for the generation of prebiotic peptides and peptide libraries within prebiotic environments.
基金supported by Beijing Advanced Innovation Center for Food Nutrition and Human Health(20181036).
文摘The purpose of this study was to screen the xanthine oxidase(XO)inhibitory peptides from egg white proteins through virtual hydrolysis,in vitro activity validation,and molecular docking.The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141μmol/L.The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions,2 salt bridges,5 conventional hydrogen bond interactions,and 4 attractive charge interactions.The residues Glu802,Phe1009,and Arg880 may play key roles in the XO catalytic reaction.Especially,the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions.The novel tripeptide EEK is potential candidates for controlling hyperuricemia.
基金The work is supported by the National Natural Science Foundation of China(grant no.21105108)Key Technology Talent Program of Chinese Academy of Sciences(2015).
文摘Diffusion-ordered nuclear magnetic resonance spectroscopy(DOSY),dubbed chromato-graphic NMR spectroscopy,can be used to simultaneously distinguish and identify the structures of components in a mixture according to their different diffusion coefficients.In order to improve the resolution of DOSY on the diffusion dimension,a lot of matrices have been developed to expand the application of this technique in mixture analysis.However,there is no matrix to detect the mixture of ionic liquids(ILs).Herein,we introduced a new matrix,poly(sodium-p-styrenesulfonate)(PSSNa),which can be used to fully separate the signals of a mixture of different ILs.The mixture of three imidazolium ILs of 1-butyl-3-methylimidazolium bromide,1-allyl-3-vinylimidazolium bromide and 1-arboxymethy-3-methylimidazolium chloride could be fully distinguished by virtue of their different interactions with PSSNa.We also investigated the influences of PSSNa amount,IL con-centration and solution pH value on the signal resolution of mixtures.This work provides a scientific reference for the analysis of the other IL analytes.
文摘The development of Chinese space science and technology plays a great role in promoting the researches in the field of the origin of life.With the multidisciplinary cooperation,there are fruitful achievements in this research field obtained over the past two years.This report summarizes the major progress of the basic researches about the origin of life in China during 2018–2020.
基金supported by the National Natural Science Foundation of China(No.21806018 and No.21873052)the Fundamental Research Funds for the Central Universities(DUT20RC(4)002)+1 种基金Scientific Research Grant of Ningbo University(No.215-432000282)Ningbo Top Talent Project(No.215-432094250)。
文摘The divergent behavior of C-H bond oxidations of aliphatic substrates compared to those of aromatic substrates shown in Gupta’s experiment was mechanistically studied herein by means of density functional theory calculations.Our calculations reveal that such difference is caused by different reaction mechanisms between two kinds of substrates(the aliphatic cyclohexane,2,3-dimethylbutane and the aromatic toluene,ethylbenzene and cumene).For the aliphatic substrates,C-H oxidation by the oxidant Fe^(V)(O)(TAML)is a hydrogen atom transfer process;whereas for the aromatic substrates,C-H oxidation is a proton-coupled electron transfer(PCET)process with a proton transfer character on the transition state,that is,a proton-coupled electron transfer process holding a proton transfer-like transition state(PCET(PT)).This difference is caused by the strongπ-πinteractions between the tetra-anionic TAML ring and the phenyl ring of the aromatic substrates,which has a“pull”effect to make the electron transfer from substrates to the Fe=O moiety inefficient.
基金support received from the Scientific Research Grant of Ningbo University(215-432000282)Ningbo Top Talent Project(215-432094250).
文摘In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.
基金the National Natural Science Foundation of China(22075154,21604044)Natural Science Foundation of Zhejiang Province(LY19B040001)Ningbo Public Welfare Science and Technology Project(2019C50072)。
文摘The interaction between the aggregation-induced emissive(AIE) luminogens(AIEgen) and the polymer is the key scientific question in the design of functional AIE hydrogels. In this study, we report the AIE behavior of a poly(acrylic acid)(PAAc) and poly(acrylamide)(PAAm) interpenetrating network(IPN) hydrogel doped with tetra-cationic tetraphenylethene(TCTPE). The cationic AIEgen can bind with PAAc through ionic interaction, while PAAc and PAAm chains can associate with each other through hydrogen-bonds(H-bonds). These two interactions can restrict the intramolecular rotation and thus activate the luminescence of the AIEgen. The PAAc-PAAm H-bonds can be broken by increasing temperature or p H, restoring the intramolecular rotation of the AIEgen and quenching the fluorescence of the hydrogel. Therefore, the TCTPE-doped IPN hydrogel is designed as temperature-and p H-sensitive displayers which can record information imprinted by photo-printing or iono-printing with good switchability and reversibility. Another application of this TCTPE-doped hydrogel is demonstrated as a luminescent soft actuator, which has fast shape deformation and editable fluorescence pattern. The above results reveal a pathway to tune the emission behavior through tuning polymer-polymer and polymer-AIEgen interactions, which may inspire new design strategies of aggregation-induced emissive polymers and broaden their applications.
基金supported by the National Natural Science Foundation of China (Nos. 21778042 and 41576081)the Fundamental Research Funds for the Central Universities(No. 20720160034)
文摘Prebiotic peptide synthesis is a central issue concerning life's origins. Many studies considered that life might come from Hadean deep-sea environment, that is, under high hydrostatic pressure conditions.However, the properties of prebiotic peptide formation under high hydrostatic pressure conditions have seldom been mentioned. Here we report that the yields of dipeptides increase with raised pressures.Significantly, effect of pressure on the formation of dipeptide was obvious at relatively low temperature.Considering that the deep sea is of high hydrostatic pressure, the pressure may serve as one of the key factors in prebiotic peptide synthesis in the Hadean deep-sea environment. The high hydrostatic pressure should be considered as one of the significant factors in studying the origin of life.
基金the National Natural Science Foundation of China(No.21105091)for financial support.
文摘A CuX-mediated regioselective halogenation reaction of 2-phenylimidazo[1,2-a]pyridine in the presence of oxygen is introduced in this paper.This reaction provides an effective method for the production of C-3 halogenated 2-phenylimidazo[1,2-a]pyridines with a yield of up to 96%.A plausible mechanism for the formation of title compounds via 2-phenylimidazo[1,2-a]pyridine–CuX complex intermediate is proposed.The structure of representative compounds is established by the single crystal XRD method.The electronic structure,corroborated by Hirshfeld surface analysis and DFT calculations,rationalizes characters of relevant absorptions and emission as well as large Stokes shifts.
基金financial support of this work from the National Natural Science Foundation of China (Nos. 21773273,21802153)。
文摘The enantioselective epoxidation of olefin by Mn^(II)(R,R-PMCP)(OTf)2, H_(2)O_(2) and H_(2)SO_(4) was explored by DFT calculations and experiments. Theoretical results suggest that [Mn^(V)(O)(R,R-PMCP)(SO_(4))]^(+) species with a triplet ground spin state serves as the active species for the olefin epoxidation. It can be generated by the H_(2)SO_(4) assisted O-O heterolysis of Mn^(III)(OOH) species. Mn^(III)-persulfate is also involved in this system, but it cannot promote the olefin epoxidation directly, preferring instead to transform into Mn^(V)(O). Actually, the asymmetric epoxidation reactions with H_(2)O_(2)/H_(2)SO_(4) or Oxone provide similar enantioselectivity in the presence of manganese catalyst. These observations further support the transformation of Mn^(III)-persulfate to Mn^(V)(O) species.
基金This work was supported by the National Natural Science Foundation of China(Nos.91856126,42003062,21778042 and 41876072)the Key Laboratory for Chemical Biology of Fujian Provinee(Xiamen University).
文摘Prebiotic peptide synthesis and the origin of the genetic code are central issues concerning the origin of life.The question of how they are possibly correlated on the primordial Earth remains perplexing,although numerous experiments have been carried out to explain the prebiotic chemistry of peptide synthesis and the genetic code origin.The purpose of this article is to review the chemical reactions occurred during the synthesis of peptides and the origin of the genetic code in the early Earth aqueous environment.Meanwhile,we attempt to review their relationship as well.At last,from our perspective,the chiral properties of biomolecules should be taken into account in the prebiotic chemical scenarios,which may contribute to some breakthroughs in the further research of this field.
基金funded by the Ningbo public welfare technology plan project(2021S012)Natural Science Foundation of Zhejiang Province(LQ2 IC 140004)K.C.Wong Magna Fund in Ningbo University.
文摘Riptortus pedestris(Fabricius),one of the major piercing-sucking insects in soybeans,causes delayed plant senescence and abnormal pods,known as staygreen syndrome.Recent research has shown that direct feeding of this insect is the major cause of soybean staygreen syndrome.However,it remains unclear whether R.pedestris salivary proteins play vital roles in insect infestation.Here,we found that 4 secretory salivary proteins can induce cell death in Nicotiana benthamiana by transient heterologous expression.The cell death induced by Rp2155 relies on the nucleotide-binding leucine-rich repeat helper,HSP90.Tissue-specificity assays indicated that Rp2155 is specifically expressed in the salivary gland of R.pedestris and is significantly induced during insect feeding.The expression of salicylic acid(SA)-,jasmonic acid(JA)-related genes was increased in soybean when fed by Rp2155-silenced R.pedestris.More importantly,soybean staygreen symptoms caused by R.pedestris were significantly alleviated when Rp2155 was silenced.Together,these results suggest that the salivary effector Rp2155 is involved in promoting insect infestation by suppressing the JA and SA pathways,and it can be considered as a potential RNA interference target for insect control.
基金Support from the National Key R&D Program of China (Nos. 2018YFA0507600, 2019YFA0904200)the National Natural Science Foundation of China (No. 92053108) is gratefully acknowledged。
文摘Amyloid proteins correlate with a series of degenerative diseases. Targeting amyloid aggregation has remained a hot topic in therapeutic studies. Numerous inhibitors have been developed, but very few have been approved for marketing. Meanwhile, the growing knowledge of amyloid structural characteristics provides a basis for the rational design of inhibitors. Here we introduce the high-resolution structural findings of amyloid fibrils in recent years and discuss the reported strategies toward rationally designed inhibitors based on amyloid-related structural studies.
基金supported by the National Key R&D Program of China(Grant No.2020YFA0608300)the Technology and Engineering Center for Space Utilization,Chinese Academy of Sciences(Grant No.YYWT-0901-EXP-16)+2 种基金the Scientific Research Grant of Ningbo University(Grant No.215-432000282)the Ningbo City Top Talent Project(Grant No.215-432094250)the National Natural Science Foundation of China(Grant Nos.22107055 and 91856126).
文摘Protein N-phosphorylation is widely present in nature and participates in various biological processes.However,current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation.In this study,we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein N-phosphorylation.Upon these substantial data,we characterized the sequential and structural features of protein N-phosphorylation.Moreover,after comparing hundreds of learning models,we chose and optimized gradient boosting decision tree(GBDT)models to predict three types of human N-phosphorylation,achieving mean area under the receiver operating characteristic curve(AUC)values of 90.56%,91.24%,and 92.01%for pHis,pLys,and pArg,respectively.Meanwhile,we discovered 488,825 distinct N-phosphosites in the human proteome.The models were also deployed in Nphos for interactive N-phosphosite prediction.In summary,this work provides new insights and points for both flexible and focused investigations of N-phosphorylation.It will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical foundation.Nphos is freely available at http://www.bio-add.org/Nphos/and http://ppodd.org.cn/Nphos/.
基金supported by National Natural Science Fundation of China(21977085,21502159 to C.Fu,91856126,21778042 to YF Zhao).
文摘Arginine phosphorylation(p Arg)is recently discovered as a ubiquitous protein N-phosphorylation in bacteria.However,its prevalence and roles in mammalian cells remain largely unknown due to the lack of established workflow and the inherent lability of phosphoramidate(P–N)bond.Emerging evidences suggest that N-phosphorylation may extensively exist in eukaryotes and play crucial roles.We report a phosphoproteomic workflow,which allows for the first time revealing the widespread occurrence of p Arg in human cells by mass spectrometry.By virtue of this approach,we identified 152 high-confidence p Arg sites derived from 118 proteins.Remarkably,the discovered p Arg phosphorylation motif and gene ontology hint a possible cellular function of arginine phosphorylation which may regulate the favorability of propeptide convertase substrate.The obtained p Arg dataset paves a way for a better understanding of the biological functions of eukaryotic p Arg in the future.
基金This work was supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)+1 种基金the National Natural Science Foundation of China(No.92053108)Applications for Chinese patents related to chitosan-mediated inhalable nanovaccine has been submitted(Patent No.202111130951.7)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),with several antigenic variants,has grown into a global challenge,and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus.This has led to a great demand for easy preparation and scalable vaccines,especially in low-income countries.Here,we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein.The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs,which might be capable of protecting the host from infection without systemic toxicity.In addition,the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2.Furthermore,inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection.This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.
基金This work was supported by the National Program on the Key Basic Research Project of China(2017YFEO108200 and 2016YFA0502302)the National Natural Science Foundation of China(NSFC)(21807105,91753119,21977110 and 21778065)+1 种基金the Strategic Priority Research Program,CAS(XDB 20000000)Center for Excellence in Molecular Synthesis,CAS(FZHCZY020600).The authors thank facility team members in National Center ofProtein Science,Shanghai(NCPSS),and High Magnetic Field La-boratory(HMFL),Chinese Academy of Sciences(CAS),Shanghailnstitute of Meteria Medica(SIMM),CAS,for their help with NMRspectra acquirement.
文摘of main observation and conclusion RET G-quadruplex DNA(G4-DNA)is formed in the promoter region of RET protein,which is involved in the initiation and progression of human cancers.Berberine inhibits cancer cell growth through interactions with RET G4-DNA,but how it binds to RET G4-DNA remains unknown.Previously,we reported that colchicine selectively bound to RET G4-DNA,but the structural basis of its binding selectivity is still unclear.Here,mainly by NMR,we demonstrated how berberine bound to RET G4-DNA in a means different from colchicine,and implied several key determinants for small molecules specifically binding to one G4-DNA.
