Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded...Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded organic frameworks(HOFs)have promising application potential for embedding enzymes.In fact,no metal involvement is required,and HOFs exhibit superior biocompatibility,and free access to substrates in mesoporous channels.Herein,a facile in situ growth approach was proposed for the self-assembly of alcohol dehydrogenase encapsulated in HOF.The micron-scale bio-catalytic composite was rapidly synthesized under mild conditions(aqueous phase and ambient temperature)with a controllable embedding rate.The high crystallinity and periodic arrangement channels of HOF were preserved at a high enzyme encapsulation efficiency of 59%.This bio-composite improved the tolerance of the enzyme to the acid-base environment and retained 81%of its initial activity after five cycles of batch hydrogenation involving NADH coenzyme.Based on this controllably synthesized bio-catalytic material and a common lipase,we further developed a two-stage cascade microchemical system and achieved the continuous production of chiral hydroxybutyric acid(R-3-HBA).展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)enters host cells via the angiotensin-converting enzyme 2(ACE2)receptor.Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)enters host cells via the angiotensin-converting enzyme 2(ACE2)receptor.Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in pa-tients with coronavirus disease 2019(COVID-19).Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19–related liver pathology and developing targeted therapies.This editorial discusses the signi-ficance of ACE2 in hepatic SARS-CoV-2 infection,drawing on the research by Jacobs et al.Their findings indicate that hepatic ACE2 expression,frequency of hepatic SARS-CoV-2 infection,and severity of liver injury are elevated in patients with pre-existing chronic liver diseases.These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.展开更多
This study was conducted at the scientific center of Brazzaville. The objective was to assess the microbial characteristics and enzymes activities in the rhizosphere soil of Cajanus cajan and Milletia lauurentii. Thes...This study was conducted at the scientific center of Brazzaville. The objective was to assess the microbial characteristics and enzymes activities in the rhizosphere soil of Cajanus cajan and Milletia lauurentii. These plants have great importance in food and forestry. Microbial diversity management in the rhizosphere is the key for sustainable crop production or forest durability. DNA metagenomic sequencing was used to analyze the whole bacterial diversity, the microbial biomass was determinate by the fumigation-extraction method and the enzymes by the p-nitrophenol-β-D-glucoside for β-glucosidase, the p-nitrophenyl-N-acetyl-β-D-glucosaminide for β-Glucosaminidase. Dehydrogenase and acid phosphatase were quantified using 2,3,5-tryphenyl tetrazolium chloride and p-nitophenylphosphate respectively. The results show that, in Cajanus cajan culturable bacteria genera were mainly Acidobacterium, Skermanella, Rhodoplanes, Bacillus, Chloroflexus, Steroidobacter, Sphingomonas and Bradyrhizobium while in Milletia laurentii: Rhodoplanes, Bradyrhizobium, Bacillus, Sphingobacterium, Acidobacterium, Mesorhizobium, Nitrospira were the principal genera. In the two rhizosphere soils investigated, the uncultured bacteria exhibited relatively higher abundance, often for the same genera, than culturable bacteria. Metagenomic studies have revealed more bacterial diversity in each compared to when culturable bacteria were taken into account alone. The MBC and MBN were higher in the rhizosphere of Milletia than in rhizosphere of Cajanus. The same trend was observed with the enzyme activities. PCA of culturable and NMDS of unculturable soil bacteria genera shows that factors mainly involved in the carbon cycle such as MBC, members of the microbial community i.e. Acidobacterium, Skermanella, Chloroflexus, sand, C, β-glucosaminidase and dehydrogenase, were strongly correlated with Cajanus cajan. On the other hand, the MBN, Mesorhizobium, Bradyrhizobium, Burkholderia, Nitrospira, Nitratireductor, N, NH4, β-glucosidase and acid phosphatase involved in the N cycling, silt and clay were predominantly founded in the rhizosphere soil of Milletia laurentii. This study showed that metagenomic sequencing could improve the assessment of the microbial diversity structure of the rhizosphere.展开更多
In recent years,chiral inorganic nanomaterials have become promising candidates for applications in sensing,catalysis,biomedicine,and photonics.Plasmonic nanomaterials with an intrinsic chiral structure exhibit intrig...In recent years,chiral inorganic nanomaterials have become promising candidates for applications in sensing,catalysis,biomedicine,and photonics.Plasmonic nanomaterials with an intrinsic chiral structure exhibit intriguing geometry‑dependent optical chirality,which benefits the combination of plasmonic characteristics with chirality.Recent advances in the biomolecule‑directed geometric control of intrinsically chiral plasmonic nanomaterials have further provided great opportunities for their widespread applications in many emerging technological areas.In this review,we present the recent progress in biosensing using chiral inorganic nanomaterials,with a particular focus on electrochemical and enzyme‑mimicking catalytic approaches.This paper commences with a review of the basic tenets underlying chiral nanocatalysts,incorporating the chiral ligand‑induced mechanism and the architectures of intrinsically chiral nanostructures.Additionally,it methodically expounds upon the applications of chiral nanocatalysts in the realms of electrochemical biosensing and enzyme‑mimicking catalytic biosensing respectively.Conclusively,it proffers a prospective view of the hurdles and prospects that accompany the deployment of chiral nanoprobes for nascent biosensing applications.By rational design of the chiral nanoprobes,it is envisioned that biosensing with increasing sensitivity and resolution toward the single‑molecule level can be achieved,which will substantially promote sensing applications in many emerging interdisciplinary areas.展开更多
UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),U...UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.展开更多
Natural enzymes are able to precisely bind substrates and catalyze activities because of their distinct framework structures.To mimic this ability,chemists are designing framework structures that resemble real enzymes...Natural enzymes are able to precisely bind substrates and catalyze activities because of their distinct framework structures.To mimic this ability,chemists are designing framework structures that resemble real enzymes.The use of metal-organic frameworks(MOFs)to mimic natural enzymes has advanced recently;this paper reviews these developments.This research specifically focuses on how the catalytically active center of natural enzymes can be exactly replicated by carefully controlling the composition and structure of MOFs.By identifying and attaching to substrates,MOFs can accelerate changes in a manner akin to that of real enzymes.The role of MOFs in simulating catalytic processes,enzyme activity,and potential uses in brain chemistry are also investigated in this work.It also discusses the most recent MOF applications in detecting and treating chemical abnormalities of the brain.The report finishes with a discussion of future research areas and potential applications,providing useful insights for researchers in the subject.展开更多
[Objectives]To prepare four kinds of fruit enzymes from pitaya(dragon fruit),papaya,orange and pineapple,and to detect their physicochemical properties and antioxidant activities.[Methods]Using pitaya,papaya,orange an...[Objectives]To prepare four kinds of fruit enzymes from pitaya(dragon fruit),papaya,orange and pineapple,and to detect their physicochemical properties and antioxidant activities.[Methods]Using pitaya,papaya,orange and pineapple as raw materials,pitaya enzyme,papaya enzyme,orange enzyme and pineapple enzyme were obtained by natural fermentation.The physical and chemical properties and antioxidant activity of the four fruit enzymes were analyzed,and the dominant strains in papaya ferment were identified.[Results]The pH of the four fruit enzymes ranged from 3.32 to 3.59.The sensory evaluation of orange and papaya enzymes was relatively superior;among them,the orange enzyme exhibited the highest hydroxyl radical scavenging rate(95.76%),while the pineapple enzyme had the highest total phenol content(27.21μg/mL).The papaya enzyme showed the highest values for DPPH,reducing power,and flavonoids,at 70.55,1.699,and 0.1216 mg/mL,respectively.Through the comprehensive comparing,the physicochemical properties and antioxidant activity of the papaya enzyme were relatively superior,with its dominant microbial species being Lactobacillus and Saccharomyces cerevisiae.[Conclusions]Papaya enzyme is a kind of functional food with great development potential,and this study can provide reference for the development of fruit enzyme with high added value.展开更多
Directed degradation of abundant renewable lignin into small aromatic compounds is crucial for lignin valorization but challenging.The degradation of lignin in natural environments typically involves multienzyme syner...Directed degradation of abundant renewable lignin into small aromatic compounds is crucial for lignin valorization but challenging.The degradation of lignin in natural environments typically involves multienzyme synergy.However,the proteinaceous characteristics of lignin-degrading enzymes restrict their accessibility to certain regions of intricate lignin,resulting in the multienzyme systems being unable to fully demonstrate their effectiveness.Herein,a de novo biomimetic enzyme-nanozyme hybrid system was constructed by combiningλ-MnO_(2) nanozyme with laccase CotA from Bacillus subtilis,aimed at facilitating lignin degradation under mild conditions.The lignin degradation rate of the CotA+λ-MnO_(2) hybrid system was determined to be 25.15%,which was much higher than those of the lignin degradation systems with only laccase CotA(15.32%)orλ-MnO_(2) nanozyme(14.90%).Notably,the proportion of aromatic chemicals in the products derived from the hybrid system reached as much as 48%,which was 41.2%and 118.2%higher than those of the CotA-andλ-MnO_(2)-catalyzed systems,respectively.Analysis of products mapping and lignin structure changes suggested that the higher proportion of aromatic compounds in the CotA+λ-MnO_(2)hybrid system was more likely to benefit from the laccase-mediated methoxylation.Moreover,electron paramagnetic resonance analysis indicated that the intensity and kind of free radicals such as·OH and·O_(2)^(-)are closely linked to the degradation rate and reaction type.This work is the inaugural application of an enzyme-nanozyme hybrid system for lignin degradation,demonstrating the potential of the synergistic interaction between enzyme and nanozyme in the directed degradation of lignin.展开更多
In order to explore the remediation effects of lignite and biochar on Zn-contaminated soil,this experiment studied the impacts of adding lignite and biochar on soil respiration,soil enzyme activity,and organic carbon ...In order to explore the remediation effects of lignite and biochar on Zn-contaminated soil,this experiment studied the impacts of adding lignite and biochar on soil respiration,soil enzyme activity,and organic carbon in Zn-contaminated soil through soil culture experiments,which provided a theoretical basis for the remediation and improvement as well as for the development and utilization of Zn-contaminated soil.The study was an L8(4×2^(2))orthogonal experimental design with eight treatments,in which there were four levels of Zn contamination concentration(Z0:0;Z1:125 mg•kg^(-1);Z2:250 mg•kg^(-1);Z3:500 mg•kg^(-1)),low-Zn(125-250 mg•kg^(-1))and high-Zn(500 mg•kg^(-1)),two levels of lignite(H0:0;H1:13.33 g•kg^(-1)),two levels of biochar(C0:0;C1:3.33 g•kg^(-1)),with four replicates per treatment.The results showed that lignite or biochar and their interaction had extremely significant effects on both respiration rate and accumulation in Zn-contaminated soil.Among the high Zn-contaminated treatments,the mixed application of lignite and biochar(Z3H1C1 treatment)had the fastest soil respiration rate and the highest soil respiration accumulation.Lignite,biochar and their interaction had significant or extremely significant effects on sucrase,catalase and polyphenol oxidase activities in Zn-contaminated soil.Among the high Zn-contaminated treatments(Z3),the addition of biochar alone had the most significant effects on the increase of soil sucrase and catalase enzyme activities,while the mixed application of lignite and biochar had the most significant effects on the increase of soil polyphenol oxidase activity.Lignite,biochar and their interaction had significant or extremely significant effects on the total organic carbon,active organic carbon and microbial carbon content of Zn-contaminated soils.Soil total organic carbon content in general peaked at day 80.Among the high Zn-contaminated treatments,the addition of biochar alone had the most significant effects on the total organic carbon content of the soil,while the mixed application of lignite and biochar had the most significant effect on the microbiomass carbon content.展开更多
Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regula...Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regulate redox bal-ance,including the mitochondrial respiratory chain,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,and different antioxidants.However,it remains unclear which redox balance compartments in the intestine are crucial for determining FE.Results In this study,we first screened the key targets of different metabolites and redox balance-related gene expression in broiler ceca.We then constructed a mouse colitis model to explore malic acid(MA)ability to allevi-ate intestinal inflammation.We further used controlled release technology to coat MA and investigated its effects on the intestinal redox status and FE in vivo.Finally,we examined the underlying mechanism by which MA modulated redox status using a porcine intestinal epithelial cell jejunum 2(IPEC-J2)cell model in vitro.Our results demonstrated that the MA/malic enzyme 3(ME3)pathway may play an important role in reducing oxidative stress in the broiler cecum.In addition,colon infusion of MA attenuated inflammatory phenotypes in the dextran sulfate sodium salt(DSS)induced mouse colitis model.Then,dietary supplementation with controlled-release MA pellet(MAP)reduced the feed to gain(F/G)ratio and promoted chicken growth,with reduced oxidative stress and increased bacterial diver-sity.Finally,the in vitro IPEC-J2 cell model revealed that ME3 mediated the effect of MA on cellular oxidative stress.Conclusion In summary,our study firstly revealed the important role of the MA/ME3 system in the hindgut of broiler chickens for improving intestinal health and FE,which may also be crucial for the implications of colon inflammation associated diseases.展开更多
Deubiquitinating enzymes(DUBs)are key enzymes capable of cleaving ubiquitin chains and synergizing with ubiquitination modifications to regulate the function of key proteins andmaintain normal physiological functions....Deubiquitinating enzymes(DUBs)are key enzymes capable of cleaving ubiquitin chains and synergizing with ubiquitination modifications to regulate the function of key proteins andmaintain normal physiological functions.OTUDs are a key subfamily of the ovarian tumor protease(OTU)family,with important DUB activities,and include mainly OTUD1,OTUD2,OTUD3,OTUD4,OTUD5,OTUD6A,and OTUD6B.In recent years,research on OTUD proteins has been gradually emphasized,and their aberrant expression has demonstrated significant research value in many diseases,such as cancer,immune abnormalities,neurological disorders,and embryonic developmental abnormalities.Therefore,a comprehensive understanding of the regulatory mechanisms of OTUD proteins and their use as therapeutic targets for diseases is of great value.This article focuses on the role of individual OTUD proteins in cancer progression and antiviral response.Importantly,in the context of cancer,we elaborate on their deubiquitinated protein targets and summarize the signaling mechanisms by which they promote or inhibit cancer progression.In the future,targeting OTUD proteins may become a therapeutic direction for cancer,and this review may be useful for research related to OTUD proteins and cancer.At present,there is a lack of research on targeted inhibitors or activators of OTUDs.More in vivo and in vitro studies on OTUDs may contribute to the development of inhibitors or agonists targeting OTUDs.Of course,when conducting these studies,researchers also need to pay attention to the impact of OTUDs on the host’s antiviral immune response.展开更多
The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying phy...The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying physiological and biochemical bases of this temperature dependence remain largely unknown.In this study,we conducted a simulated climate warming experiment under seminatural enclosure conditions and compared the differences in resting metabolic rate (RMR) and key metabolic enzyme activities between the warming and control groups of Takydromus septentrionalis at various test temperatures.We found that the activities of hexokinase,lactate dehydrogenase,alanine aminotransferase and acetyl-CoA carboxylase of T.septentrionalis were not affected by climate warming,despite a decrease in RMR measured at high temperatures of 34°C and 38°C.Overall,these findings suggest that artificial warming simulating climate change can lead to a decline in RMR,but does not alter the activity of key metabolic enzymes.Our study provides insight into how climate warming influences the energy metabolism of lizards.展开更多
The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfu...The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.展开更多
DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide ...DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide convincing evidence based on the comparison of the activity of multiple enzymes than on that of single enzyme.Although fluorescence approach has been applied for the simultaneous detection both of DNA repair enzymes,the spectral overlap and multiwavelength excitation severely restrict the number of available fluorophores.Thus,it is difficult to simultaneously detect three enzymes in a single analysis by fluorescence detection.Herein,we developed a method for the simultaneous determination of three DNA repair enzymes including human flap DNA endonuclease 1(FEN1),human alkyladenine DNA glycosylase(hAAG)and uracil DNA glycosylase(UDG)based on the combination of template-free amplification system with capillary electrophoresis-laser induced fluorescence(CE-LIF)detection.The amplification system was adopted to transfer and amplify the enzymatic products into different length DNA fragments which could be separated effectively by CE-LIF without the complicated modification of the capillary inner wall or labeling different tails on signal probes for separation.The method demonstrated a detection limit of 0.07 U/mL(0.08-160 U/mL)for FEN1,2.40 U/mL(2.5-250U/mL)for hAAG and 2.1×10^(-4)U/mL(0.0004-2.5 U/mL)for UDG,the relative standard deviations(RSDs)of peak time and peak area for different analytes were as follows:2.50%-4,37%and 3.24%-7.18%(inter-day);1.37%-2.71%and 1.43%-3.02%(intra-day),4.28%-6.08%and 4.16%-7.57%(column to column),respectively.And it can identify the inhibitor-like drugs,evaluate enzymatic kinetics and achieve the detection of three enzymes in cell extracts,providing a simple and powerful platform for simultaneous detection of more DNA repair enzymes.展开更多
Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating h...Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating hormonal homeostasis.In the ubiquitination cascade,ubiquitin-conjugating enzymes(UBCs)function as ubiquitin carriers to determine linkage specificity of ubiquitin chains.In rice(Oryza sativa),39 UBC genes are identified,but only one gene OsUBC12 has been functionally studied to promote seed germination under low-temperatures in japonica rice.To elucidate the role of UBCs in seed germination,we generated CRISPR-Cas9 mutants for 23 UBC genes and overexpressed 20 members in rice.Among them,seven UBC genes(OsUBC4/6/7/12/25/27/48)were found to regulate seed germination,with OsUBC27 and OsUBC48 acting through the ABA pathway.Exogenous ABA inhibitors restored the germination rate of osubc27^(CR).RT-qPCR analysis revealed that the ABA synthesis genes OsNCED1-5 were significantly upregulated in the mutants.Further differential ubiquitination proteomics in knockout mutants and wild-type plants showed that OsUBC27 regulates ABA homeostasis by modulating ubiquitination of the ABA-degrading protein OsABA8ox1,thereby balancing seed dormancy and germination.Sequence analysis identified distinct haplotypes of the seven OsUBCs that showed differential distribution between japonica and indica subspecies.Our study provides valuable molecular targets for developing rice varieties resistant to seed vivipary.展开更多
BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown m...BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown mixed effects on liver function,with varying safety profiles among agents.AIM To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes.METHODS A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1,2019,and September 30,2024.Out of the patients screened,9 met the inclusion criteria.Trends in liver enzymes,fibrosis-4(FIB-4)score,and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods.RESULTS Among 9 patients(4 on adalimumab,5 on etanercept),the median age was 56 years[interquartile range(IQR):49.5–64.5 years],77.8%were female,and the median body mass index was 36.99 kg/m²(IQR:30.95–43.43 kg/m²).Median baseline FIB-4 was 1.25(IQR:1.02–1.65),with no cirrhosis observed at baseline.Aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase levels declined consistently,with significant reductions from baseline to 3 years(P=0.003).FIB-4 scores also significantly decreased(P=0.003),while albumin,bilirubin,and Child-Pugh class remained stable at the 3-year follow-up.At 3 years,66.7%achieved RA remission(P=0.03).CONCLUSION TNFi therapy(adalimumab or etanercept)was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation,supporting its safety in our cohort of RA patients with liver involvement.Larger prospective studies are warranted to further validate these findings.展开更多
To investigate the correlation between propacetamol and postoperative liver enzyme abnormalities among patients,a retrospective analysis was conducted on inpatients in the thoracic surgery department spanning from Jan...To investigate the correlation between propacetamol and postoperative liver enzyme abnormalities among patients,a retrospective analysis was conducted on inpatients in the thoracic surgery department spanning from January 1 to June 30,2023.Causality assessment regarding propacetamol and postoperative liver enzyme abnormalities was performed using the updated Roussel Uclaf Causality Assessment Method(RUCAM).Furthermore,independent risk factors for liver enzyme abnormalities were identified through both univariate and multivariate analyses,followed by the construction and validation of a clinical nomogram.A total of 247 patients who received propacetamol were ultimately included in the study.Liver enzyme abnormalities post-surgery were more accurately predicted by considering the daily dose of propacetamol and the number of medications(OR(95%CI),4.831(2.797,8.344),P<0.001;10.007(3.878,25.823),P<0.001).A clinical predictive nomogram model was developed,incorporating these two independent risk factors,which exhibited favorable discrimination(AUC(95%CI),0.811(0.750,0.872)),calibration,and decision curve analysis(DCA)demonstrating the highest net benefits across a broad spectrum of threshold probabilities(10%to 90%).The daily dose of propacetamol and the number of medications were found to be independently associated with postoperative liver enzyme abnormalities.This user-friendly nomogram,comprising these two factors,might assist clinicians in assessing the risks of propacetamol-related liver dysfunction following surgery.展开更多
Hydrogen-bonded framework(HOF) offers an attractive platform to encapsulate enzymes and stabilize their conformation,due to the advantages of mild synthesis conditions,tailorable pore structure,and backbone biocompati...Hydrogen-bonded framework(HOF) offers an attractive platform to encapsulate enzymes and stabilize their conformation,due to the advantages of mild synthesis conditions,tailorable pore structure,and backbone biocompatibility.However,the efficiency of this HOF approach relies on the interfacial interactions between enzyme vip and the ligand precursors,limiting its adaptability to enzymes with varying surface chemistry property.In this study,we report a site-specific surface modification strategy to positively tailor the enzyme surface charge,facilitating the biomimetic encapsulation of enzymes within HOF in situ.Both experimental results and computational simulation reveal that site-specific amination of enzyme surface's acidic residues contributes to the interfacial accumulation of carboxylic ligand precursors in aqueous solutions via synergistic electrostatic and hydrogen bonding interactions.This substantially facilitates the in situ growth of porous HOF surrounding the aminated enzyme biotemplates,with up to 100% enzyme loading efficiency.The resultant hydrogen-bonded biohybrid framework(HBF) retains high biocatalytic functions while exhibiting exceptional stability under harsh conditions.By leveraging the marked catalytic activity of GOx-NH_(2)@HBF-1 and a H_(2)O_(2)-sensitive QD,a highly sensitive glucose fluorescence sensor is fabricated with a wide linear range(5-2000 μmol/L) and a low quantification limit of 5 μmol/L.This work presents a simple yet effective enzyme surface engineering approach for integrating enzyme into HOF,opening new avenues for the construction of multifunctional HOF biocomposites.展开更多
The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metab...The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metabolomics,and soil properties.Thus,in this study,the long-term impact of coke combustion on soil microbial community structure,enzyme activities,and metabolic pathways within a former coking plant site was investigated.Soil samples were collected from both the coking production area(CA group)and office area(OLA group),approximately 0 to 20 cm in depth.Compared with OLA group,elevated levels of 16 PAHs in the list of US EPA were detected by gas chromatography-mass spectrometry in the CA group.Several dominant microorganisms,such as Altererythrobacter,Lysobacter,and Sulfurifustis,were identified by 16 s ribosomal DNA sequencing in the CA group.The fatty acid biosynthesis pathway exhibited specific inhibition,while the phenylalanine metabolic pathwaywas promoted in response to PAH stress.Long-term PAH exposure led to the inhibition of soil urease activity.The co-occurrence network ofmicroorganisms revealed intricate patterns of co-metabolism and co-adaptation within complex bacterial communities,facilitating their adaptation to and decomposition of soil-borne PAHs.This research could provide valuable insights into the community characteristics andmetabolic mechanisms of microorganisms inhabiting PAH-polluted soil within coking plant sites.The findings enhance our understanding of the indigenous soil microbiome and its intricate network dynamics under the persistent stress of PAHs,contributing to a more comprehensive knowledge of soil ecosystems in such environments.展开更多
Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify...Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.展开更多
基金supported by the National Key Research and Development Program of China(2019YFA0905100)the National Natural Science Foundation of China(21991102,22378227).
文摘Constructing a framework carrier to stabilize protein conformation,induce high embedding efficiency,and acquire low mass-transfer resistance is an urgent issue in the development of immobilized enzymes.Hydrogen-bonded organic frameworks(HOFs)have promising application potential for embedding enzymes.In fact,no metal involvement is required,and HOFs exhibit superior biocompatibility,and free access to substrates in mesoporous channels.Herein,a facile in situ growth approach was proposed for the self-assembly of alcohol dehydrogenase encapsulated in HOF.The micron-scale bio-catalytic composite was rapidly synthesized under mild conditions(aqueous phase and ambient temperature)with a controllable embedding rate.The high crystallinity and periodic arrangement channels of HOF were preserved at a high enzyme encapsulation efficiency of 59%.This bio-composite improved the tolerance of the enzyme to the acid-base environment and retained 81%of its initial activity after five cycles of batch hydrogenation involving NADH coenzyme.Based on this controllably synthesized bio-catalytic material and a common lipase,we further developed a two-stage cascade microchemical system and achieved the continuous production of chiral hydroxybutyric acid(R-3-HBA).
基金Supported by National Natural Science Foundation of China,No.82172915,No.81972648,and No.81773011Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0084+1 种基金Science and Technology Innovation Project of Chongqing Medical Universityand Chongqing Postdoctoral Science Foundation,No.CSTB2023NSCQ-BHX0134.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)enters host cells via the angiotensin-converting enzyme 2(ACE2)receptor.Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in pa-tients with coronavirus disease 2019(COVID-19).Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19–related liver pathology and developing targeted therapies.This editorial discusses the signi-ficance of ACE2 in hepatic SARS-CoV-2 infection,drawing on the research by Jacobs et al.Their findings indicate that hepatic ACE2 expression,frequency of hepatic SARS-CoV-2 infection,and severity of liver injury are elevated in patients with pre-existing chronic liver diseases.These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.
文摘This study was conducted at the scientific center of Brazzaville. The objective was to assess the microbial characteristics and enzymes activities in the rhizosphere soil of Cajanus cajan and Milletia lauurentii. These plants have great importance in food and forestry. Microbial diversity management in the rhizosphere is the key for sustainable crop production or forest durability. DNA metagenomic sequencing was used to analyze the whole bacterial diversity, the microbial biomass was determinate by the fumigation-extraction method and the enzymes by the p-nitrophenol-β-D-glucoside for β-glucosidase, the p-nitrophenyl-N-acetyl-β-D-glucosaminide for β-Glucosaminidase. Dehydrogenase and acid phosphatase were quantified using 2,3,5-tryphenyl tetrazolium chloride and p-nitophenylphosphate respectively. The results show that, in Cajanus cajan culturable bacteria genera were mainly Acidobacterium, Skermanella, Rhodoplanes, Bacillus, Chloroflexus, Steroidobacter, Sphingomonas and Bradyrhizobium while in Milletia laurentii: Rhodoplanes, Bradyrhizobium, Bacillus, Sphingobacterium, Acidobacterium, Mesorhizobium, Nitrospira were the principal genera. In the two rhizosphere soils investigated, the uncultured bacteria exhibited relatively higher abundance, often for the same genera, than culturable bacteria. Metagenomic studies have revealed more bacterial diversity in each compared to when culturable bacteria were taken into account alone. The MBC and MBN were higher in the rhizosphere of Milletia than in rhizosphere of Cajanus. The same trend was observed with the enzyme activities. PCA of culturable and NMDS of unculturable soil bacteria genera shows that factors mainly involved in the carbon cycle such as MBC, members of the microbial community i.e. Acidobacterium, Skermanella, Chloroflexus, sand, C, β-glucosaminidase and dehydrogenase, were strongly correlated with Cajanus cajan. On the other hand, the MBN, Mesorhizobium, Bradyrhizobium, Burkholderia, Nitrospira, Nitratireductor, N, NH4, β-glucosidase and acid phosphatase involved in the N cycling, silt and clay were predominantly founded in the rhizosphere soil of Milletia laurentii. This study showed that metagenomic sequencing could improve the assessment of the microbial diversity structure of the rhizosphere.
文摘In recent years,chiral inorganic nanomaterials have become promising candidates for applications in sensing,catalysis,biomedicine,and photonics.Plasmonic nanomaterials with an intrinsic chiral structure exhibit intriguing geometry‑dependent optical chirality,which benefits the combination of plasmonic characteristics with chirality.Recent advances in the biomolecule‑directed geometric control of intrinsically chiral plasmonic nanomaterials have further provided great opportunities for their widespread applications in many emerging technological areas.In this review,we present the recent progress in biosensing using chiral inorganic nanomaterials,with a particular focus on electrochemical and enzyme‑mimicking catalytic approaches.This paper commences with a review of the basic tenets underlying chiral nanocatalysts,incorporating the chiral ligand‑induced mechanism and the architectures of intrinsically chiral nanostructures.Additionally,it methodically expounds upon the applications of chiral nanocatalysts in the realms of electrochemical biosensing and enzyme‑mimicking catalytic biosensing respectively.Conclusively,it proffers a prospective view of the hurdles and prospects that accompany the deployment of chiral nanoprobes for nascent biosensing applications.By rational design of the chiral nanoprobes,it is envisioned that biosensing with increasing sensitivity and resolution toward the single‑molecule level can be achieved,which will substantially promote sensing applications in many emerging interdisciplinary areas.
基金Supported by Special Projects in Key Areas for Guangdong Provincial Colleges and Universities (No.2021ZDZX2009)Guangzhou Medical University Discipline Construction Funds (Basic Medicine)(No.JCXKJS2022A05)。
文摘UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.
基金financially supported by the National Natural Science Foundation,China(Nos.22074095&22374103(Y.Lin))Beijing Natural Science Foundation(No.2222005(Y.Lin))。
文摘Natural enzymes are able to precisely bind substrates and catalyze activities because of their distinct framework structures.To mimic this ability,chemists are designing framework structures that resemble real enzymes.The use of metal-organic frameworks(MOFs)to mimic natural enzymes has advanced recently;this paper reviews these developments.This research specifically focuses on how the catalytically active center of natural enzymes can be exactly replicated by carefully controlling the composition and structure of MOFs.By identifying and attaching to substrates,MOFs can accelerate changes in a manner akin to that of real enzymes.The role of MOFs in simulating catalytic processes,enzyme activity,and potential uses in brain chemistry are also investigated in this work.It also discusses the most recent MOF applications in detecting and treating chemical abnormalities of the brain.The report finishes with a discussion of future research areas and potential applications,providing useful insights for researchers in the subject.
文摘[Objectives]To prepare four kinds of fruit enzymes from pitaya(dragon fruit),papaya,orange and pineapple,and to detect their physicochemical properties and antioxidant activities.[Methods]Using pitaya,papaya,orange and pineapple as raw materials,pitaya enzyme,papaya enzyme,orange enzyme and pineapple enzyme were obtained by natural fermentation.The physical and chemical properties and antioxidant activity of the four fruit enzymes were analyzed,and the dominant strains in papaya ferment were identified.[Results]The pH of the four fruit enzymes ranged from 3.32 to 3.59.The sensory evaluation of orange and papaya enzymes was relatively superior;among them,the orange enzyme exhibited the highest hydroxyl radical scavenging rate(95.76%),while the pineapple enzyme had the highest total phenol content(27.21μg/mL).The papaya enzyme showed the highest values for DPPH,reducing power,and flavonoids,at 70.55,1.699,and 0.1216 mg/mL,respectively.Through the comprehensive comparing,the physicochemical properties and antioxidant activity of the papaya enzyme were relatively superior,with its dominant microbial species being Lactobacillus and Saccharomyces cerevisiae.[Conclusions]Papaya enzyme is a kind of functional food with great development potential,and this study can provide reference for the development of fruit enzyme with high added value.
文摘Directed degradation of abundant renewable lignin into small aromatic compounds is crucial for lignin valorization but challenging.The degradation of lignin in natural environments typically involves multienzyme synergy.However,the proteinaceous characteristics of lignin-degrading enzymes restrict their accessibility to certain regions of intricate lignin,resulting in the multienzyme systems being unable to fully demonstrate their effectiveness.Herein,a de novo biomimetic enzyme-nanozyme hybrid system was constructed by combiningλ-MnO_(2) nanozyme with laccase CotA from Bacillus subtilis,aimed at facilitating lignin degradation under mild conditions.The lignin degradation rate of the CotA+λ-MnO_(2) hybrid system was determined to be 25.15%,which was much higher than those of the lignin degradation systems with only laccase CotA(15.32%)orλ-MnO_(2) nanozyme(14.90%).Notably,the proportion of aromatic chemicals in the products derived from the hybrid system reached as much as 48%,which was 41.2%and 118.2%higher than those of the CotA-andλ-MnO_(2)-catalyzed systems,respectively.Analysis of products mapping and lignin structure changes suggested that the higher proportion of aromatic compounds in the CotA+λ-MnO_(2)hybrid system was more likely to benefit from the laccase-mediated methoxylation.Moreover,electron paramagnetic resonance analysis indicated that the intensity and kind of free radicals such as·OH and·O_(2)^(-)are closely linked to the degradation rate and reaction type.This work is the inaugural application of an enzyme-nanozyme hybrid system for lignin degradation,demonstrating the potential of the synergistic interaction between enzyme and nanozyme in the directed degradation of lignin.
基金Supported by the Special Fund for Agro-scientific Research in Public Interest in China(201503119-06-01)。
文摘In order to explore the remediation effects of lignite and biochar on Zn-contaminated soil,this experiment studied the impacts of adding lignite and biochar on soil respiration,soil enzyme activity,and organic carbon in Zn-contaminated soil through soil culture experiments,which provided a theoretical basis for the remediation and improvement as well as for the development and utilization of Zn-contaminated soil.The study was an L8(4×2^(2))orthogonal experimental design with eight treatments,in which there were four levels of Zn contamination concentration(Z0:0;Z1:125 mg•kg^(-1);Z2:250 mg•kg^(-1);Z3:500 mg•kg^(-1)),low-Zn(125-250 mg•kg^(-1))and high-Zn(500 mg•kg^(-1)),two levels of lignite(H0:0;H1:13.33 g•kg^(-1)),two levels of biochar(C0:0;C1:3.33 g•kg^(-1)),with four replicates per treatment.The results showed that lignite or biochar and their interaction had extremely significant effects on both respiration rate and accumulation in Zn-contaminated soil.Among the high Zn-contaminated treatments,the mixed application of lignite and biochar(Z3H1C1 treatment)had the fastest soil respiration rate and the highest soil respiration accumulation.Lignite,biochar and their interaction had significant or extremely significant effects on sucrase,catalase and polyphenol oxidase activities in Zn-contaminated soil.Among the high Zn-contaminated treatments(Z3),the addition of biochar alone had the most significant effects on the increase of soil sucrase and catalase enzyme activities,while the mixed application of lignite and biochar had the most significant effects on the increase of soil polyphenol oxidase activity.Lignite,biochar and their interaction had significant or extremely significant effects on the total organic carbon,active organic carbon and microbial carbon content of Zn-contaminated soils.Soil total organic carbon content in general peaked at day 80.Among the high Zn-contaminated treatments,the addition of biochar alone had the most significant effects on the total organic carbon content of the soil,while the mixed application of lignite and biochar had the most significant effect on the microbiomass carbon content.
基金supported by the local innovative and research teams project of Guangdong province(2019BT02N630)national key research and development program(2022YFD1300401)+2 种基金Double first-class discipline promoting project(2023B10564001)National Natural Science Foundation of China(32272954)Natural Science Foundation of Guangdong Province,China(2024A1515013131).
文摘Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regulate redox bal-ance,including the mitochondrial respiratory chain,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,and different antioxidants.However,it remains unclear which redox balance compartments in the intestine are crucial for determining FE.Results In this study,we first screened the key targets of different metabolites and redox balance-related gene expression in broiler ceca.We then constructed a mouse colitis model to explore malic acid(MA)ability to allevi-ate intestinal inflammation.We further used controlled release technology to coat MA and investigated its effects on the intestinal redox status and FE in vivo.Finally,we examined the underlying mechanism by which MA modulated redox status using a porcine intestinal epithelial cell jejunum 2(IPEC-J2)cell model in vitro.Our results demonstrated that the MA/malic enzyme 3(ME3)pathway may play an important role in reducing oxidative stress in the broiler cecum.In addition,colon infusion of MA attenuated inflammatory phenotypes in the dextran sulfate sodium salt(DSS)induced mouse colitis model.Then,dietary supplementation with controlled-release MA pellet(MAP)reduced the feed to gain(F/G)ratio and promoted chicken growth,with reduced oxidative stress and increased bacterial diver-sity.Finally,the in vitro IPEC-J2 cell model revealed that ME3 mediated the effect of MA on cellular oxidative stress.Conclusion In summary,our study firstly revealed the important role of the MA/ME3 system in the hindgut of broiler chickens for improving intestinal health and FE,which may also be crucial for the implications of colon inflammation associated diseases.
文摘Deubiquitinating enzymes(DUBs)are key enzymes capable of cleaving ubiquitin chains and synergizing with ubiquitination modifications to regulate the function of key proteins andmaintain normal physiological functions.OTUDs are a key subfamily of the ovarian tumor protease(OTU)family,with important DUB activities,and include mainly OTUD1,OTUD2,OTUD3,OTUD4,OTUD5,OTUD6A,and OTUD6B.In recent years,research on OTUD proteins has been gradually emphasized,and their aberrant expression has demonstrated significant research value in many diseases,such as cancer,immune abnormalities,neurological disorders,and embryonic developmental abnormalities.Therefore,a comprehensive understanding of the regulatory mechanisms of OTUD proteins and their use as therapeutic targets for diseases is of great value.This article focuses on the role of individual OTUD proteins in cancer progression and antiviral response.Importantly,in the context of cancer,we elaborate on their deubiquitinated protein targets and summarize the signaling mechanisms by which they promote or inhibit cancer progression.In the future,targeting OTUD proteins may become a therapeutic direction for cancer,and this review may be useful for research related to OTUD proteins and cancer.At present,there is a lack of research on targeted inhibitors or activators of OTUDs.More in vivo and in vitro studies on OTUDs may contribute to the development of inhibitors or agonists targeting OTUDs.Of course,when conducting these studies,researchers also need to pay attention to the impact of OTUDs on the host’s antiviral immune response.
基金supported by the National Natural Science Foundation of China (Grant Nos.32330067,31971419,32311530110,and 32171486)。
文摘The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying physiological and biochemical bases of this temperature dependence remain largely unknown.In this study,we conducted a simulated climate warming experiment under seminatural enclosure conditions and compared the differences in resting metabolic rate (RMR) and key metabolic enzyme activities between the warming and control groups of Takydromus septentrionalis at various test temperatures.We found that the activities of hexokinase,lactate dehydrogenase,alanine aminotransferase and acetyl-CoA carboxylase of T.septentrionalis were not affected by climate warming,despite a decrease in RMR measured at high temperatures of 34°C and 38°C.Overall,these findings suggest that artificial warming simulating climate change can lead to a decline in RMR,but does not alter the activity of key metabolic enzymes.Our study provides insight into how climate warming influences the energy metabolism of lizards.
基金National Natural Science Foundation of China(22073023)Natural Science Foundation of Henan Province(242300421134)+1 种基金the Young Backbone Teacher in Colleges and Universities of Henan Province(2021GGJS020)Foundation of State Key Laboratory of Antiviral Drugs。
文摘The acetylpolyamine oxidase(APAO),spermine oxidase(SMO),and spermidine/spermine N1-acetyltransferase(SSAT)are pivotal enzymes in polyamine metabolism,exerting direct influence on polyamine homeostasis regulation.Dysfunctions in these enzymes are intricately linked to inflammatory diseases and cancers.Establishing their three-dimensional structures is essential for exploring enzymatic catalytic mechanisms and designing inhibitors at the atomic level.This article primarily assesses the precision of AlphaFold2 and molecular dynamics simulations in determining the three-dimensional structures of these enzymes,utilizing protein conformation rationality assessment,residue correlation matrix,and other techniques.This provides robust models for subsequent polyamine catabolic metabolism calculations and offers valuable insights for modeling proteins that have yet to acquire crystal structures.
基金supported by the National Natural Science Foundation of China(Nos.21874060 and 22174058,U21A20282)the Science and Technology program of Gansu Province(No.22JR5RA476)。
文摘DNA repair enzymes are important in the repair of DNA lesions for maintaining the genome stability,and their abnormal expression induced various human cancers.Simultaneous detection of these DNA enzymes could provide convincing evidence based on the comparison of the activity of multiple enzymes than on that of single enzyme.Although fluorescence approach has been applied for the simultaneous detection both of DNA repair enzymes,the spectral overlap and multiwavelength excitation severely restrict the number of available fluorophores.Thus,it is difficult to simultaneously detect three enzymes in a single analysis by fluorescence detection.Herein,we developed a method for the simultaneous determination of three DNA repair enzymes including human flap DNA endonuclease 1(FEN1),human alkyladenine DNA glycosylase(hAAG)and uracil DNA glycosylase(UDG)based on the combination of template-free amplification system with capillary electrophoresis-laser induced fluorescence(CE-LIF)detection.The amplification system was adopted to transfer and amplify the enzymatic products into different length DNA fragments which could be separated effectively by CE-LIF without the complicated modification of the capillary inner wall or labeling different tails on signal probes for separation.The method demonstrated a detection limit of 0.07 U/mL(0.08-160 U/mL)for FEN1,2.40 U/mL(2.5-250U/mL)for hAAG and 2.1×10^(-4)U/mL(0.0004-2.5 U/mL)for UDG,the relative standard deviations(RSDs)of peak time and peak area for different analytes were as follows:2.50%-4,37%and 3.24%-7.18%(inter-day);1.37%-2.71%and 1.43%-3.02%(intra-day),4.28%-6.08%and 4.16%-7.57%(column to column),respectively.And it can identify the inhibitor-like drugs,evaluate enzymatic kinetics and achieve the detection of three enzymes in cell extracts,providing a simple and powerful platform for simultaneous detection of more DNA repair enzymes.
基金supported by the Zhejiang Provincial Natural Science Foundation,China(ZCLMS25C1302)the Central Public-interest Scientific Institution Basal Research Fund(CPSIBRF-CNRRI-202408)the Agricultural Science and Technology Innovation Program(ASTIP)
文摘Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating hormonal homeostasis.In the ubiquitination cascade,ubiquitin-conjugating enzymes(UBCs)function as ubiquitin carriers to determine linkage specificity of ubiquitin chains.In rice(Oryza sativa),39 UBC genes are identified,but only one gene OsUBC12 has been functionally studied to promote seed germination under low-temperatures in japonica rice.To elucidate the role of UBCs in seed germination,we generated CRISPR-Cas9 mutants for 23 UBC genes and overexpressed 20 members in rice.Among them,seven UBC genes(OsUBC4/6/7/12/25/27/48)were found to regulate seed germination,with OsUBC27 and OsUBC48 acting through the ABA pathway.Exogenous ABA inhibitors restored the germination rate of osubc27^(CR).RT-qPCR analysis revealed that the ABA synthesis genes OsNCED1-5 were significantly upregulated in the mutants.Further differential ubiquitination proteomics in knockout mutants and wild-type plants showed that OsUBC27 regulates ABA homeostasis by modulating ubiquitination of the ABA-degrading protein OsABA8ox1,thereby balancing seed dormancy and germination.Sequence analysis identified distinct haplotypes of the seven OsUBCs that showed differential distribution between japonica and indica subspecies.Our study provides valuable molecular targets for developing rice varieties resistant to seed vivipary.
文摘BACKGROUND Elevated liver enzymes in rheumatoid arthritis(RA)are often attributed to multiple factors including disease activity and treatment-related adverse effects.Tumor necrosis factor inhibitors(TNFi)have shown mixed effects on liver function,with varying safety profiles among agents.AIM To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes.METHODS A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1,2019,and September 30,2024.Out of the patients screened,9 met the inclusion criteria.Trends in liver enzymes,fibrosis-4(FIB-4)score,and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods.RESULTS Among 9 patients(4 on adalimumab,5 on etanercept),the median age was 56 years[interquartile range(IQR):49.5–64.5 years],77.8%were female,and the median body mass index was 36.99 kg/m²(IQR:30.95–43.43 kg/m²).Median baseline FIB-4 was 1.25(IQR:1.02–1.65),with no cirrhosis observed at baseline.Aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase levels declined consistently,with significant reductions from baseline to 3 years(P=0.003).FIB-4 scores also significantly decreased(P=0.003),while albumin,bilirubin,and Child-Pugh class remained stable at the 3-year follow-up.At 3 years,66.7%achieved RA remission(P=0.03).CONCLUSION TNFi therapy(adalimumab or etanercept)was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation,supporting its safety in our cohort of RA patients with liver involvement.Larger prospective studies are warranted to further validate these findings.
基金The Medical Education Research Program of Henan Province,China(Grant No.WJLX2023015)and the Chinese International Medical Foundation for Clinical Pharmacy,China(Grant No.Z-2021-46-2101).
文摘To investigate the correlation between propacetamol and postoperative liver enzyme abnormalities among patients,a retrospective analysis was conducted on inpatients in the thoracic surgery department spanning from January 1 to June 30,2023.Causality assessment regarding propacetamol and postoperative liver enzyme abnormalities was performed using the updated Roussel Uclaf Causality Assessment Method(RUCAM).Furthermore,independent risk factors for liver enzyme abnormalities were identified through both univariate and multivariate analyses,followed by the construction and validation of a clinical nomogram.A total of 247 patients who received propacetamol were ultimately included in the study.Liver enzyme abnormalities post-surgery were more accurately predicted by considering the daily dose of propacetamol and the number of medications(OR(95%CI),4.831(2.797,8.344),P<0.001;10.007(3.878,25.823),P<0.001).A clinical predictive nomogram model was developed,incorporating these two independent risk factors,which exhibited favorable discrimination(AUC(95%CI),0.811(0.750,0.872)),calibration,and decision curve analysis(DCA)demonstrating the highest net benefits across a broad spectrum of threshold probabilities(10%to 90%).The daily dose of propacetamol and the number of medications were found to be independently associated with postoperative liver enzyme abnormalities.This user-friendly nomogram,comprising these two factors,might assist clinicians in assessing the risks of propacetamol-related liver dysfunction following surgery.
基金financial support from projects of the National Natural Science Foundation of China(Nos.22104159,22174164)Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515011632,2024B1515020070)。
文摘Hydrogen-bonded framework(HOF) offers an attractive platform to encapsulate enzymes and stabilize their conformation,due to the advantages of mild synthesis conditions,tailorable pore structure,and backbone biocompatibility.However,the efficiency of this HOF approach relies on the interfacial interactions between enzyme vip and the ligand precursors,limiting its adaptability to enzymes with varying surface chemistry property.In this study,we report a site-specific surface modification strategy to positively tailor the enzyme surface charge,facilitating the biomimetic encapsulation of enzymes within HOF in situ.Both experimental results and computational simulation reveal that site-specific amination of enzyme surface's acidic residues contributes to the interfacial accumulation of carboxylic ligand precursors in aqueous solutions via synergistic electrostatic and hydrogen bonding interactions.This substantially facilitates the in situ growth of porous HOF surrounding the aminated enzyme biotemplates,with up to 100% enzyme loading efficiency.The resultant hydrogen-bonded biohybrid framework(HBF) retains high biocatalytic functions while exhibiting exceptional stability under harsh conditions.By leveraging the marked catalytic activity of GOx-NH_(2)@HBF-1 and a H_(2)O_(2)-sensitive QD,a highly sensitive glucose fluorescence sensor is fabricated with a wide linear range(5-2000 μmol/L) and a low quantification limit of 5 μmol/L.This work presents a simple yet effective enzyme surface engineering approach for integrating enzyme into HOF,opening new avenues for the construction of multifunctional HOF biocomposites.
基金supported by the National Key Research and Development Program of China(Nos.2018YFA0901100 and 2018YFC1801103)the National Natural Science Foundation of China(Nos.22206202 and 22076216)。
文摘The problem of soil polycyclic aromatic hydrocarbon(PAH)pollution in coking plant sites has been widely studied in recent years,but there is a lack of research on the correlation between soil microorganisms,soil metabolomics,and soil properties.Thus,in this study,the long-term impact of coke combustion on soil microbial community structure,enzyme activities,and metabolic pathways within a former coking plant site was investigated.Soil samples were collected from both the coking production area(CA group)and office area(OLA group),approximately 0 to 20 cm in depth.Compared with OLA group,elevated levels of 16 PAHs in the list of US EPA were detected by gas chromatography-mass spectrometry in the CA group.Several dominant microorganisms,such as Altererythrobacter,Lysobacter,and Sulfurifustis,were identified by 16 s ribosomal DNA sequencing in the CA group.The fatty acid biosynthesis pathway exhibited specific inhibition,while the phenylalanine metabolic pathwaywas promoted in response to PAH stress.Long-term PAH exposure led to the inhibition of soil urease activity.The co-occurrence network ofmicroorganisms revealed intricate patterns of co-metabolism and co-adaptation within complex bacterial communities,facilitating their adaptation to and decomposition of soil-borne PAHs.This research could provide valuable insights into the community characteristics andmetabolic mechanisms of microorganisms inhabiting PAH-polluted soil within coking plant sites.The findings enhance our understanding of the indigenous soil microbiome and its intricate network dynamics under the persistent stress of PAHs,contributing to a more comprehensive knowledge of soil ecosystems in such environments.
基金the High-level construction discipline of the National Administration of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.
