BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational mo...BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.展开更多
Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Imp...Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.展开更多
Succinylation is a highly conserved post-translational modication that is processed via enzymatic and non-enzymatic mechanisms.Succinylation exhibits strong effects on protein stability,enzyme activity,and transcripti...Succinylation is a highly conserved post-translational modication that is processed via enzymatic and non-enzymatic mechanisms.Succinylation exhibits strong effects on protein stability,enzyme activity,and transcriptional regulation.Protein succinylation is extensively present in the liver,and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism.For instance,histone acetyltransferase 1 promotes liver glycolysis,and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism.Therefore,the effects of succinylation on hepatic glucose,amino acid,and lipid metabolism under the action of various enzymes will be discussed in this work.In addition,how succinylases regulate the progression of different liver diseases will be reviewed,including the desuccinylation activity of sirtuin 7,which is closely associated with fatty liver disease and hepatitis,and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma.In view of the diversity and significance of protein succinylation,targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.展开更多
Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In t...Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue(cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.展开更多
Dear Editor,Lysine residue succinylation is a novel post-translational modification that recently attracted extensive attention.Succinylation is achieved by non-enzymatic processes or by a series of enzymes[like p300,...Dear Editor,Lysine residue succinylation is a novel post-translational modification that recently attracted extensive attention.Succinylation is achieved by non-enzymatic processes or by a series of enzymes[like p300,lysine acetyltransferase 2A(KAT2A)]that transfer the succinyl groups from succinyl-coenzyme A(CoA)to the specific lysine,modulating protein function in various physiological processes[1].As a high-energy metabolite,succinyl-CoA is mainly produced within the mitochondrial matrix and peroxisomes.Its high-rate generation in the tricarboxylic acid(TCA)cycle and its impermeability across the mitochondrial inner membrane(due to its negative charge property)enhance succinyl-CoA accumulation within mitochondria.展开更多
As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiom...As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiometabolic,liver metabolic,nervous system and so on.Therefore,it is imperative to predict the succinylation sites in proteins for both basic research and drug development.In this paper,a novel predictor called i Succ Lys-BLS was proposed by not only introducing a new machine learning algorithm—Broad Learning System,but also optimizing the imbalanced data by randomly labeling samples.Rigorous cross-validation and independent test indicate that the success rate of i Succ Lys-BLS for positive samples is overwhelmingly higher than its counterparts.展开更多
Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acety...Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acetyltransferase 1(HAT1)confers reprogramming of gluconeogenesis/lipogenesis in liver cancer.Diethylnitrosamine(DEN)/carbon tetrachloride(CCl4)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice.Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver.Protein phosphatase 2 scaffold subunit alpha(PPP2R1A)promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1(PCK1)serine 90 dephosphorylation to suppress the tumor growth.HAT1 succinylated PPP2R1A at lysine 541(K541)to block the assembly of protein phosphatase 2A(PP2A)holoenzyme and interaction with PCK1,resulting in the depression of dephosphorylation of PCK1.HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation,leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1(SREBP1)nuclear accumulation-induced lipogenesis gene expression,which enhanced the tumor growth.In conclusion,succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer.Our finding provides new insights into the mechanism by which post-translational modifications(PTMs)confer the conversion of tumor suppressor function to oncogene.展开更多
Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to e...Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis.The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis(eCRS).Methods:Our study investigated the role of Sirt5 gene expression in both non-eCRS and eCRS.We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration.Additionally,we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease.To further understand the underlying mechanisms,we conducted experiments at the single-cell level using bone marrow-derived eosinophils.We validated our findings through in vitro culture of eosinophils and intervention experiments.Through these experiments,we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.Results:There is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa.Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS-affected nasal mucosa.Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2,a critical gene in the amino acid biosynthesis pathway.Conclusions:The severity of eCRS is closely associated with the expression level of Sirt5.Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils,thereby influencing metabolic remodeling and functional activation in eCRS.Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies.This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.展开更多
Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic...Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic,and evolutionarily conserved^4 where it has been comprehensively studied in both bacterial and mammalian cells^5-7.Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated^5-7.Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases,including cardiovascular diseases and cancer^7-9.Therefore,an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases.In this review,we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.展开更多
Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.H...Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.However,studies in this field are limited by the difficulty in experimentally identifying the substrate site specificity of lysine succinylation.To facilitate this process,several tools have been proposed for the computational identification of succinylated lysine sites.In this study,we developed an approach to investigate the substrate specificity of lysine succinylated sites based on amino acid composition.Using experimentally verified lysine succinylated sites collected from public resources,the significant differences in position-specific amino acid composition between succinylated and non-succinylated sites were represented using the Two Sample Logo program.These findings enabled the adoption of an effective machine learning method,support vector machine,to train a predictive model with not only the amino acid composition,but also the composition of k-spaced amino acid pairs.After the selection of the best model using a ten-fold crossvalidation approach,the selected model significantly outperformed existing tools based on an independent dataset manually extracted from published research articles.Finally,the selected model was used to develop a web-based tool,SuccSite,to aid the study of protein succinylation.Two proteins were used as case studies on the website to demonstrate the effective prediction of succinylation sites.We will regularly update SuccSite by integrating more experimental datasets.SuccSite is freely accessible at http://csb.cse.yzu.edu.tw/SuccSite/.展开更多
Ketone bodies have beneficial metabolic activities,and the induction of plasma ketone bodies is a health promotion strategy.Dietary supplementation of sodium butyrate(SB)is an effective approach in the induction of pl...Ketone bodies have beneficial metabolic activities,and the induction of plasma ketone bodies is a health promotion strategy.Dietary supplementation of sodium butyrate(SB)is an effective approach in the induction of plasma ketone bodies.However,the cellular and molecular mechanisms are unknown.In this study,SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2),a rate-limiting enzyme in ketogenesis,to promote ketone body production in hepatocytes.SB administrated by gavage or intraperitoneal injection significantly induced bloodβ-hydroxybutyrate(BHB)in mice.BHB production was induced in the primary hepatocytes by SB.Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis.However,the alteration was mostly observed in mitochondrial proteins with 41%down-and 65%up-regulation,respectively.Succinylation status of HMGCS2 protein was altered by a reduction at two sites(K221 and K358)without a change in the protein level.The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice.The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver.The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis.The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.展开更多
Lysine succinylation is a naturally occurring post-translational modification(PTM)that regulates the stability and function of proteins.It can be regulated by enzymes such as SIRT5 and SIRT7.Recently,the effect and si...Lysine succinylation is a naturally occurring post-translational modification(PTM)that regulates the stability and function of proteins.It can be regulated by enzymes such as SIRT5 and SIRT7.Recently,the effect and significance of lysine succinylation in cancer and its implication in immunity have been extensively explored.Lysine succinylation is involved in the malignant phenotype of cancer cells.Abnormal regulation of lysine succinylation occurs in different cancers,and inhibitors targeting lysine succinylation regulatory enzymes can be used as potential anti-cancer strategies.Therefore,this review focused on the target protein lysine succinylation and its functions in cancer and immunity,in order to provide a reference for finding more potential clinical cancer targets in the future.展开更多
Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Re...Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes,such as tumor-igenesis and metabolic diseases.To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms,we reviewed the current literature about Ksuc,mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools.We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical prac-tice.A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.展开更多
As an important protein acylation modification,lysine succinylation(Ksucc)is involved in diverse biological processes,and participates in human tumorigenesis.Here,we collected 26,243 non-redundant known Ksucc sites fr...As an important protein acylation modification,lysine succinylation(Ksucc)is involved in diverse biological processes,and participates in human tumorigenesis.Here,we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set,combined 10 types of informative features,and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework.We constructed a new tool named HybridSucc,which achieved area under curve(AUC)values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites,respectively.In comparison,the accuracy of HybridSucc was 17.84%-50.62%better than that of other existing tools.Using HybridSucc,we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins,including PKM2,SHMT2,and IDH2.We not only developed a high-profile tool for predicting Ksucc sites,but also generated useful candidates for further experimental consideration.The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.展开更多
The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain f...The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.展开更多
Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide canno...Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.展开更多
This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by opt...This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by optimization of single factor study and Box–Beehnkendesign. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochem-ical properties of S-WPIs dried by different three methods on their flow ability, particle size,morphology and in vitro release behavior were studied. After preparing PR-5 sustained re-lease protein tablets with S-WPIs as the carrier by direct powder compression method, thedrug release were studied in vitro and the oral pharmacokinetics and bioavailability wasevaluated using in vivo dog model. It was observed that concentration of substrate has asignificant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism(protein loss). Comparedwith PR-5 conventional tablet with oral administration, T max value of PR-5 sustained-releaseprotein tablets was approximately 1.58 fold greater than those of the conventional tablets asfurther evidenced by the significantly prolonged MRT and T 1/2. The findings demonstratedthat spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability.展开更多
An environmentally friendly organic biosorbent was fabricated using hay by succinylation. Metallic cation adsorption tests were performed using synthetic nickel(Ⅱ) and cadmium(Ⅱ) solutions to simulate heavy-metal re...An environmentally friendly organic biosorbent was fabricated using hay by succinylation. Metallic cation adsorption tests were performed using synthetic nickel(Ⅱ) and cadmium(Ⅱ) solutions to simulate heavy-metal recovery from aqueous solution. The adsorption efficiency was greater than 98% for both cadmium and nickel ions when the biosorbent concentration was 5.0 g/L and the initial metal concentrations were 50 mg/L. The surface of the biosorbent was characterized using Fourier transform infrared spectroscopy to investigate the changes in the surface functional groups. The functional groups changed according to the surface treatment, resulting in an effective biosorbent. The kinetics of the metals adsorption revealed that the reactions are pseudo-second order, and the adsorption isotherm well followed the Langmuir model. The maximum adsorption capacities predicted by the Langmuir model were 75.19 mg/g and 57.77 mg/g for cadmium and nickel, respectively. The fabricated biosorbent was regenerated using Na Cl multiple times, with 2.1% for Cd and 4.0% for Ni in adsorption capacity after three regeneration cycles. The proposed biosorbent can be a good alternative to resin or other chemical adsorbents for heavy-metal recovery in metallurgical processing or municipal water treatment.展开更多
Many native proteins possess limited functionality, and modification such as succinylation is often performed to expand the range of functional properties available for pharmaceutical dosage form. Succinylation could ...Many native proteins possess limited functionality, and modification such as succinylation is often performed to expand the range of functional properties available for pharmaceutical dosage form. Succinylation could be useful for modulating protein-based system swelling and drug delivery properties especially for sustained controlled release dosage form like microsphere. A well designed controlled drug delivery system can overcome the problems of conventional drug therapy and gives better therapeutic efficacy of a drug.展开更多
Chemically modified pullulan was evaluated for its sorption efficiency and selectivity to remove cadmium（Cd） from spiked high-hardness groundwater（GW）. Pullulan esterified with succinic anhydride using dimethylami...Chemically modified pullulan was evaluated for its sorption efficiency and selectivity to remove cadmium（Cd） from spiked high-hardness groundwater（GW）. Pullulan esterified with succinic anhydride using dimethylaminopyridine showed a fairly high degree of substitution value as confirmed by1 H NMR spectroscopy. Pullulan succinate（Pull-Suc） was converted into the sodium salt（Pull-Suc-Na）. The effect of contact time（5–200 min） and p H（2–8） on Cd-uptake by the sorbent（Pull-Suc-Na） was investigated. The sorbent showed more than 90% Cd-removal in first 15 min from distilled water（DW） and GW solution,respectively. Comparison of Pull-Suc-Na with other polysaccharidal sorbents suggested its high efficiency（DW 476.2 mg/g and GW 454.5 mg/g） and selectivity for the removal of Cd by an ion exchange mechanism, which is further supported by the negative Gibbs free energy values calculated from Langmuir isotherms. A Langmuir isotherm kinetic model provided the best fit for the sorption of Cd using Pull-Suc-Na. The sorbent showed a negligible decrease in Cd-uptake over three regeneration cycles. The thermal stability testing of the sorbents indicated that Pull-Suc-Na（sorbent） is more stable than Pull-Suc.展开更多
基金Supported by National Natural Science Foundation of China,No.82000579 and No.81870205Natural Science Foundation of Shandong Province,No.ZR2021QH061 and No.ZR2021QH186.
文摘BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.
基金supported by the National Natural Science Foundation of China,No.82071283(to QH)the Natural Science Foundation of Shanghai,No.22ZR1437700(to QH)。
文摘Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.
文摘Succinylation is a highly conserved post-translational modication that is processed via enzymatic and non-enzymatic mechanisms.Succinylation exhibits strong effects on protein stability,enzyme activity,and transcriptional regulation.Protein succinylation is extensively present in the liver,and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism.For instance,histone acetyltransferase 1 promotes liver glycolysis,and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism.Therefore,the effects of succinylation on hepatic glucose,amino acid,and lipid metabolism under the action of various enzymes will be discussed in this work.In addition,how succinylases regulate the progression of different liver diseases will be reviewed,including the desuccinylation activity of sirtuin 7,which is closely associated with fatty liver disease and hepatitis,and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma.In view of the diversity and significance of protein succinylation,targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.
基金supported by the National Natural Science Foundation of China,No. 81671164 (to SHQ)the Natural Science Foundation of Jiangsu Province of China,No. BK20211348 (to SHQ)Xuzhou Basic Research Program,No. KC21030 (to LYH)。
文摘Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue(cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.
基金the Guangdong Natural Science Research Grant(2019A1515010196).
文摘Dear Editor,Lysine residue succinylation is a novel post-translational modification that recently attracted extensive attention.Succinylation is achieved by non-enzymatic processes or by a series of enzymes[like p300,lysine acetyltransferase 2A(KAT2A)]that transfer the succinyl groups from succinyl-coenzyme A(CoA)to the specific lysine,modulating protein function in various physiological processes[1].As a high-energy metabolite,succinyl-CoA is mainly produced within the mitochondrial matrix and peroxisomes.Its high-rate generation in the tricarboxylic acid(TCA)cycle and its impermeability across the mitochondrial inner membrane(due to its negative charge property)enhance succinyl-CoA accumulation within mitochondria.
基金the National Natural Science Foundation of China(61761023,31760315)the Natural Science Foundation of Jiangxi Province,China(20202BABL202004,20202BAB202007)the Scientific Research Plan of the Department of Education of Jiangxi Province(GJJ190695)。
文摘As one important type of post-translational modifications(PTMs),protein lysine succinylation regulates many important biological processes.It is also closely involved with some major diseases in the aspects of Cardiometabolic,liver metabolic,nervous system and so on.Therefore,it is imperative to predict the succinylation sites in proteins for both basic research and drug development.In this paper,a novel predictor called i Succ Lys-BLS was proposed by not only introducing a new machine learning algorithm—Broad Learning System,but also optimizing the imbalanced data by randomly labeling samples.Rigorous cross-validation and independent test indicate that the success rate of i Succ Lys-BLS for positive samples is overwhelmingly higher than its counterparts.
基金supported by the National Natural Science Foundation of China(Nos.82103066,82372818,82303210,and 82302887)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A,China).
文摘Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acetyltransferase 1(HAT1)confers reprogramming of gluconeogenesis/lipogenesis in liver cancer.Diethylnitrosamine(DEN)/carbon tetrachloride(CCl4)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice.Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver.Protein phosphatase 2 scaffold subunit alpha(PPP2R1A)promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1(PCK1)serine 90 dephosphorylation to suppress the tumor growth.HAT1 succinylated PPP2R1A at lysine 541(K541)to block the assembly of protein phosphatase 2A(PP2A)holoenzyme and interaction with PCK1,resulting in the depression of dephosphorylation of PCK1.HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation,leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1(SREBP1)nuclear accumulation-induced lipogenesis gene expression,which enhanced the tumor growth.In conclusion,succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer.Our finding provides new insights into the mechanism by which post-translational modifications(PTMs)confer the conversion of tumor suppressor function to oncogene.
基金funded by the National Natural Science Foundation of China:81541038,81670905,81870702.
文摘Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis.The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis(eCRS).Methods:Our study investigated the role of Sirt5 gene expression in both non-eCRS and eCRS.We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration.Additionally,we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease.To further understand the underlying mechanisms,we conducted experiments at the single-cell level using bone marrow-derived eosinophils.We validated our findings through in vitro culture of eosinophils and intervention experiments.Through these experiments,we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.Results:There is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa.Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS-affected nasal mucosa.Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2,a critical gene in the amino acid biosynthesis pathway.Conclusions:The severity of eCRS is closely associated with the expression level of Sirt5.Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils,thereby influencing metabolic remodeling and functional activation in eCRS.Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies.This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.
基金We apologize to any authors whose work could not be included owing to space limitations.This work was supported in part by NIH R01 CA225680-01(T.H.)Research Scholar Grant(RSG-19-076-01-TBE)from the American Cancer Society(T.H.)Career Catalyst Research funding(CCR14300798)from the Susan G.Komen Foundation(T.H.),the Eagles Cancer Research Fund(T.H.),a Team Science Platform Award from the Mayo Clinic Center for Biomedical Discovery(T.H.),the Developmental Therapeutics Program from the Mayo Clinic Cancer Center(T.H.),and the Mayo Clinic Breast SPORE P50CA 116201-10(T.H.).E.K.W.was supported by a predoctoral fellowship from the Mayo Foundation for Education and Research.
文摘Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic,and evolutionarily conserved^4 where it has been comprehensively studied in both bacterial and mammalian cells^5-7.Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated^5-7.Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases,including cardiovascular diseases and cancer^7-9.Therefore,an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases.In this review,we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.
基金the Warshel Institute for Computational Biology,School of Life and Health Sciences,The Chinese University of Hong Kong,Shenzhen,China for financially supporting this research
文摘Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.However,studies in this field are limited by the difficulty in experimentally identifying the substrate site specificity of lysine succinylation.To facilitate this process,several tools have been proposed for the computational identification of succinylated lysine sites.In this study,we developed an approach to investigate the substrate specificity of lysine succinylated sites based on amino acid composition.Using experimentally verified lysine succinylated sites collected from public resources,the significant differences in position-specific amino acid composition between succinylated and non-succinylated sites were represented using the Two Sample Logo program.These findings enabled the adoption of an effective machine learning method,support vector machine,to train a predictive model with not only the amino acid composition,but also the composition of k-spaced amino acid pairs.After the selection of the best model using a ten-fold crossvalidation approach,the selected model significantly outperformed existing tools based on an independent dataset manually extracted from published research articles.Finally,the selected model was used to develop a web-based tool,SuccSite,to aid the study of protein succinylation.Two proteins were used as case studies on the website to demonstrate the effective prediction of succinylation sites.We will regularly update SuccSite by integrating more experimental datasets.SuccSite is freely accessible at http://csb.cse.yzu.edu.tw/SuccSite/.
基金supported by the National Key Research and Development Program of China(No.2018YFA0800603)a project(No.19ZR1439000)of the Shanghai Association for Science and Technology to Jianping Ye.
文摘Ketone bodies have beneficial metabolic activities,and the induction of plasma ketone bodies is a health promotion strategy.Dietary supplementation of sodium butyrate(SB)is an effective approach in the induction of plasma ketone bodies.However,the cellular and molecular mechanisms are unknown.In this study,SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2),a rate-limiting enzyme in ketogenesis,to promote ketone body production in hepatocytes.SB administrated by gavage or intraperitoneal injection significantly induced bloodβ-hydroxybutyrate(BHB)in mice.BHB production was induced in the primary hepatocytes by SB.Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis.However,the alteration was mostly observed in mitochondrial proteins with 41%down-and 65%up-regulation,respectively.Succinylation status of HMGCS2 protein was altered by a reduction at two sites(K221 and K358)without a change in the protein level.The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice.The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver.The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis.The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
基金supported by Youth Wan Jiang Scholar of Anhui Province,China(No.DT2100001172)Beijing Xisike Clinical Oncology Research Foundation(China)(No.Y-HR2020MS-0156).
文摘Lysine succinylation is a naturally occurring post-translational modification(PTM)that regulates the stability and function of proteins.It can be regulated by enzymes such as SIRT5 and SIRT7.Recently,the effect and significance of lysine succinylation in cancer and its implication in immunity have been extensively explored.Lysine succinylation is involved in the malignant phenotype of cancer cells.Abnormal regulation of lysine succinylation occurs in different cancers,and inhibitors targeting lysine succinylation regulatory enzymes can be used as potential anti-cancer strategies.Therefore,this review focused on the target protein lysine succinylation and its functions in cancer and immunity,in order to provide a reference for finding more potential clinical cancer targets in the future.
基金supported by National Natural Science Foundation of China(No.82002172)Key Scientific Research Project Plan of Henan Province(No.20A180001)Innovation program of Henan university students(No.202110475033,20217003003).
文摘Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes,such as tumor-igenesis and metabolic diseases.To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms,we reviewed the current literature about Ksuc,mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools.We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical prac-tice.A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.
基金supported by the Special Project on Precision Medicine under the National Key R&D Program of China(Grant Nos.2017YFC0906600 and 2018YFC0910500)the National Natural Science Foundation of China(Grant Nos.31671360,31801095,and 31601067)+4 种基金Fundamental Research Funds for the Central Universities(Grant Nos.2019kfyRCPY043 and 2017KFXKJC001)the National Program for Support of Top-Notch Young ProfessionalsChangjiang Scholars Program of Chinaprogram for HUST Academic Frontier Youth TeamChina Postdoctoral Science Foundation(Grant No.2018M632870)
文摘As an important protein acylation modification,lysine succinylation(Ksucc)is involved in diverse biological processes,and participates in human tumorigenesis.Here,we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set,combined 10 types of informative features,and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework.We constructed a new tool named HybridSucc,which achieved area under curve(AUC)values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites,respectively.In comparison,the accuracy of HybridSucc was 17.84%-50.62%better than that of other existing tools.Using HybridSucc,we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins,including PKM2,SHMT2,and IDH2.We not only developed a high-profile tool for predicting Ksucc sites,but also generated useful candidates for further experimental consideration.The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.
基金supported by the Natural Science Foundation Project of China(81820108015,82201683)China Postdoctoral Science Foundation(2021M693926,2020TQ0393,2020M683634XB)+1 种基金Chongqing Science&Technology Commission(cstc2021jcyj-bshX0150,cstc2021jcyj-bshX0201)Special Funding for Chongqing Postdoctoral Research Projects(2021XMT001)。
文摘The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.
基金support from National Natural Science Foundation of China(Nos.22077103 and 22161132006)Westlake University startup。
文摘Histone H3K79 modifications are essential to regulate chromatin structure and gene transcription,but understanding of the molecular mechanisms is limited.Because H3K79 is at globular domain,short histone peptide cannot mimic H3K79 in chromatin.Instead,reconstituted nucleosome-based chemical tools are ideally used to investigate H3K79 modifications.In consequence,H3K79-modified histone H3 with additional chemical handles are required,but such synthesis is challenging and laborious.Here we report a facile semisynthesis method that enables multifunctional histone H3 readily available.H3K79-containing fragment is short for straight peptide synthesis that was later ligated to recombinant expressed H3 fragments for full-length product in large scale.As a result,nucleosomes with H3K79 modifications as well as photo-reactive group and affinity tag were obtained to investigate potential binding proteins.We believe this method that enhances synthetic accessibility of nucleosome probes will accelerate understanding of the underexplored H3K79 modifications.
文摘This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by optimization of single factor study and Box–Beehnkendesign. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochem-ical properties of S-WPIs dried by different three methods on their flow ability, particle size,morphology and in vitro release behavior were studied. After preparing PR-5 sustained re-lease protein tablets with S-WPIs as the carrier by direct powder compression method, thedrug release were studied in vitro and the oral pharmacokinetics and bioavailability wasevaluated using in vivo dog model. It was observed that concentration of substrate has asignificant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism(protein loss). Comparedwith PR-5 conventional tablet with oral administration, T max value of PR-5 sustained-releaseprotein tablets was approximately 1.58 fold greater than those of the conventional tablets asfurther evidenced by the significantly prolonged MRT and T 1/2. The findings demonstratedthat spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability.
文摘An environmentally friendly organic biosorbent was fabricated using hay by succinylation. Metallic cation adsorption tests were performed using synthetic nickel(Ⅱ) and cadmium(Ⅱ) solutions to simulate heavy-metal recovery from aqueous solution. The adsorption efficiency was greater than 98% for both cadmium and nickel ions when the biosorbent concentration was 5.0 g/L and the initial metal concentrations were 50 mg/L. The surface of the biosorbent was characterized using Fourier transform infrared spectroscopy to investigate the changes in the surface functional groups. The functional groups changed according to the surface treatment, resulting in an effective biosorbent. The kinetics of the metals adsorption revealed that the reactions are pseudo-second order, and the adsorption isotherm well followed the Langmuir model. The maximum adsorption capacities predicted by the Langmuir model were 75.19 mg/g and 57.77 mg/g for cadmium and nickel, respectively. The fabricated biosorbent was regenerated using Na Cl multiple times, with 2.1% for Cd and 4.0% for Ni in adsorption capacity after three regeneration cycles. The proposed biosorbent can be a good alternative to resin or other chemical adsorbents for heavy-metal recovery in metallurgical processing or municipal water treatment.
文摘Many native proteins possess limited functionality, and modification such as succinylation is often performed to expand the range of functional properties available for pharmaceutical dosage form. Succinylation could be useful for modulating protein-based system swelling and drug delivery properties especially for sustained controlled release dosage form like microsphere. A well designed controlled drug delivery system can overcome the problems of conventional drug therapy and gives better therapeutic efficacy of a drug.
基金the Higher Education Commission, Pakistan, for funding under the scheme "HEC Indigenous 5000 Fellowships" with grant number PIN 074-1392-Ps4-584
文摘Chemically modified pullulan was evaluated for its sorption efficiency and selectivity to remove cadmium（Cd） from spiked high-hardness groundwater（GW）. Pullulan esterified with succinic anhydride using dimethylaminopyridine showed a fairly high degree of substitution value as confirmed by1 H NMR spectroscopy. Pullulan succinate（Pull-Suc） was converted into the sodium salt（Pull-Suc-Na）. The effect of contact time（5–200 min） and p H（2–8） on Cd-uptake by the sorbent（Pull-Suc-Na） was investigated. The sorbent showed more than 90% Cd-removal in first 15 min from distilled water（DW） and GW solution,respectively. Comparison of Pull-Suc-Na with other polysaccharidal sorbents suggested its high efficiency（DW 476.2 mg/g and GW 454.5 mg/g） and selectivity for the removal of Cd by an ion exchange mechanism, which is further supported by the negative Gibbs free energy values calculated from Langmuir isotherms. A Langmuir isotherm kinetic model provided the best fit for the sorption of Cd using Pull-Suc-Na. The sorbent showed a negligible decrease in Cd-uptake over three regeneration cycles. The thermal stability testing of the sorbents indicated that Pull-Suc-Na（sorbent） is more stable than Pull-Suc.
