[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ab...[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ability and reducing capacity of DPPH as well as inhibitory rate of nonenzymatic glycation reaction were measured targets for comparing changes of anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of fermentation lyophilizer and fermentation extraction before and after EGB fermention adsorbed by AB-8 macroporous resin. The EGB fermention was biotransformed by Hericium erinaceus. [ Result ] After adsorbed by AB-8 macroporous resin, the bioactive matters were concentrated and separated. The free radical scavenging rate, reducing capacity and inhibitory rate of nonenzymatic glycation reaction were increased significantly after adsorbed by AB-8 macroporous resin. [ Conclusion] AB-8 macroporous resin could be used for preliminary concentration of EGB fermentation which was biotransformed by Hericium erinaceus.展开更多
The multiwalled carbon nanotubes thin-film-based electrode was fabricated by electrophoretic deposition and modified with copper （Cu） nanoparticles to fabricate Cu/CNTs nanocomposite sensor for nonenzymatic glucose ...The multiwalled carbon nanotubes thin-film-based electrode was fabricated by electrophoretic deposition and modified with copper （Cu） nanoparticles to fabricate Cu/CNTs nanocomposite sensor for nonenzymatic glucose detection. The expensive glassy carbon electrode was replaced by fluorine-doped tin oxide glass containing CNTs film to confine the Cu nanoparticles growth by electrodeposition through cyclic voltammetry （CV）. The ultraviolet visible and X-ray diffraction analysis revealed the successful deposition of Cu nanoparticles on the CNTs-modified electrode. The atomic force microscopy images confirrqed the morphology of electrodeposited Cu on CNTs film as uniformly dispersed particles. The electrocatalytic activity of electrode to the glucose oxidation was investigated in alkaline medium by CV and amperometric measurements. The fabricated sensor exhibited a fast response time of less than 5 s and the sensitivity of 314 μA rnM^-1 cm^-2 with linear concentration range （0.02-3.0 mM） having detection limit 10.0 μM. Due to simple preparation of sensor, Cu/CNTs nanocomposite electrodes are a suitable candidate for reliable determination of glucose with good stability.展开更多
A novel nonenzymatic glucose sensor was successfully fabricated based on the Cu2O polyhedrons covered Cu foil. The Cu2O polyhedrons covered Cu foil was constructed via a facile, low-cost and larger scale producible me...A novel nonenzymatic glucose sensor was successfully fabricated based on the Cu2O polyhedrons covered Cu foil. The Cu2O polyhedrons covered Cu foil was constructed via a facile, low-cost and larger scale producible method. The Cu2O polyhedrons covered Cu foil can be directly used as the working electrode of nonenzymatic glucose sensor, which present good stability and flexibility. The results indicated that the Cu2O polyhedrons modified Cu electrode （Cu2O/Cu electrode） showed high electrocatalytic activity for the oxidation of glucose in alkaline solution. There are two linear regions of glucose concentration for the glucose sensor based on Cu2O/Cu electrode, respectively in 10μmol/L to 0.53 mmol/L （sensitivity： 3029.33 μA （mmol/ L）^-1 cm^-2） and in 0.53-7.53 mmol/L （sensitivity： 728.67 μA （rnmol/L）^-1 cm^-2）.展开更多
Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displ...Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displacement(TMSD)and branch migration.With their sensitive and efficient signal amplification capabilities,NDARs have become essential tools for biomarker detection and intracellular imaging.They encompass four primary amplification methods:catalytic hairpin assembly(CHA),hybridization chain reaction(HCR),DNAzyme-based amplification,and entropy-driven circuits(EDC).Based on amplification mechanisms,NDARs can be categorized into three types:stimuli-responsive NDARs,which employ single amplification strategies triggered by specific stimuli like pH,light,or biomolecules;cascade NDARs,which integrate two or more amplification reactions for stepwise signal enhancement;and autocatalytic NDARs,which achieve exponential amplification through self-sustained cycling.These advanced designs progressively improve amplification efficiency,enhance sensitivity,and minimize background noise,enabling precise detection of proteins,viruses,and nucleic acids as well as applications in cancer cell imaging and therapy.Compared with classical NDARs,these approaches significantly reduce signal leakage,offering broader applicability in diagnostics,imaging,and therapeutic contexts.This review summarizes recent advancements,addresses existing challenges,and explores future directions,providing insights into the development and applications of NDARs.展开更多
D-Allulose 3-epimerase(DAEase)is a biocatalyst of concern for D-allulose enzymatic synthesis;however,it exhibits comparatively low thermal stability.To facilitate the directed evolution of DAEase,a nonenzymatic colori...D-Allulose 3-epimerase(DAEase)is a biocatalyst of concern for D-allulose enzymatic synthesis;however,it exhibits comparatively low thermal stability.To facilitate the directed evolution of DAEase,a nonenzymatic colorimetric assay was developed for high-throughput screening of enhanced DAEase mutants.One desirable mutant,MT4(S38F/F42N/A70P/T119P),was screened based on purifying selection of the randomly muta-genesis library and positive screening of the randomly shuffled library.Compared to the wild-type,the combi-national mutant MT4 had higher catalytic activity(1.23-fold)and showed 5,6.2,and 6.92℃ increases in T_(opt),T_(50),and T_(m) values,respectively.Furthermore,at 60℃,the t_(1/2) value of mutant MT4 was 7.30nullh,exhibiting an 11.4-fold increase in comparison to the wild-type.When the mutant MT4 was used in D-allulose production,the yield reached 28.3%,higher than the 25.1%achieved by the wild-type.Dynamic property and structural change analysis demonstrated that the enhanced properties of mutant MT4 were largely attributed to theβ4-α4 loop rigidification and active-site tunnel entrance constriction.This work expands the industrial application value of DAEase and provides a robust method as the basis for further protein engineering to achieve better performance of this enzyme.展开更多
With increasing emphasis on green chemistry,biomass-based materials have attracted increased attention regarding the development of highly efficient functional materials.Herein,a new pore-rich cellulose nanofibril aer...With increasing emphasis on green chemistry,biomass-based materials have attracted increased attention regarding the development of highly efficient functional materials.Herein,a new pore-rich cellulose nanofibril aerogel is utilized as a substrate to integrate highly conductive polypyrrole and active nanoflower-like nickel-cobalt layered double hydroxide through in situ chemical polymerization and electrodeposition.This ternary composite can act as an effective self-supported electrode for the electrocatalytic oxidation of glucose.With the synergistic effect of three heterogeneous components,the electrode achieves outstanding glucose sensing performance,including a high sensitivity(851.4μA·mmol^(−1)·L·cm^(−2)),a short response time(2.2 s),a wide linear range(two stages:0.001−8.145 and 8.145−35.500 mmol·L^(−1)),strong immunity to interference,outstanding intraelectrode and interelectrode reproducibility,a favorable toxicity resistance(Cl^(‒)),and a good long-term stability(maintaining 86.0%of the original value after 30 d).These data are superior to those of some traditional glucose sensors using nonbiomass substrates.When determining the blood glucose level of a human serum,this electrode realizes a high recovery rate of 97.07%–98.89%,validating the potential for highperformance blood glucose sensing.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
A nonenzymatic electrochemical sensor for glucose and fructose was fabricated that contained a glassy carbon electrode modified with a copper oxide (CuO)/multiwalled carbon nanotube (MWCNT) nanocomposite. The electroc...A nonenzymatic electrochemical sensor for glucose and fructose was fabricated that contained a glassy carbon electrode modified with a copper oxide (CuO)/multiwalled carbon nanotube (MWCNT) nanocomposite. The electrochemical properties of the CuO/MWCNT‐modified glassy carbon electrode were investigated. Two distinguishable anodic peaks were observed around 0.30 and 0.44 V corresponding to the oxidation of glucose and fructose, respectively, at the surface of the modified electrode. The detection limits for glucose and fructose were both 0.04 mmol/L. The sensor was used to simultaneously determine the concentrations of glucose and fructose in hydrolyzed sucrose samples, and to measure glucose in blood serum samples, demonstrating its potential as a nonenzymatic carbohydrate sensor.展开更多
Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side...Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side chains.These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways.Stachbotrydial(2)with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines.In the present work,an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono-and diamines in the fungus Stachybotrys chartarum cultures.In total,24 phenylspirodrimane lactams(1,3-25)including 18 new compounds were synthesized.Among them,stachybocin A(1),a bioactive phenylspirodrimane lactam dimer,was produced with the yield of 18.7 mg/g of cell dry weight.The structures of these compounds were elucidated by extensive spectroscopic data,single-crystal X-ray diffraction(Cu Kα),and calculated electronic circular dichroism(ECD)analyses.Bioassay revealed that compounds 1,17,and 24 displayed significant inhibitory effect on the inactivated state of hNav 1.2 channels with IC_(50) values of 0.22,2.08,and 0.53μmol/L,respectively.In addition,1 showed potent protein tyrosine phosphatase 1B(PTP1B)inhibitory N-methyl-b-aspartate(NMDA)receptor antagonistic,and anti-inflammatory activities.展开更多
Racemization of aspartic acid (Asp) residues in proteins plays an important role in the molecular biology of aging. In the widely accepted mechanism of the Asp racemization, a succinimide (SI) intermediate is the spec...Racemization of aspartic acid (Asp) residues in proteins plays an important role in the molecular biology of aging. In the widely accepted mechanism of the Asp racemization, a succinimide (SI) intermediate is the species which actually undergo the direct racemization. In the present study, a two-water-assisted mechanism of the SI racemization was computationally investigated using a model compound in which an aminosuccinyl (Asu) residue is capped with acetyl and NMe groups on the N-and C-termini, respectively. The two water molecules catalyze the enolization of the Hα-Cα-C=O portion in the Asu residue by mediating proton relay from the α-carbon atom to the carboxyl oxygen atom. After the enolization, migration of the water molecules and conformational change lead to the mirror image of the initially formed enol two-water complex, and the racemization is completed by the following ketonization. The overall activation barrier (28.2 kcal·mol-1) corresponds to the enolization and ketonization steps, and falls within the available experimental activation energies (21.4-29.0 kcal·mol-1). Therefore, the two-water-assisted mechanism investigated here is plausible for the in vivo and in vitro racemization reactions of the SI intermediates formed in peptides and proteins.展开更多
Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study d...Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study describes the generation of 15 new halogenated angucyclinones through the incorporation of halogen-containing phenylamines into a biosynthetic C-ringcleaved angucyclinone under mild conditions.The newly synthesized compounds feature halogen substituents encompassing all four halogen atoms(F,Cl,Br,I),with some compounds containing multiple halogen types.Structural elucidation was accomplished through ultraviolet(UV),infrared spectroscopy(IR),mass spectrometry(MS),and nuclear magnetic resonance(NMR)spectroscopic analyses,expanding the structural diversity of angucyclinonetype polyketides.Cytotoxicity evaluations revealed that eight compounds demonstrated moderate cytotoxic activities against four human tumor cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.35±0.37 to 16.02±6.60μmol·L-1.These findings highlight the significant potential of combining biosynthetic and chemical approaches in generating bioactive halogenated molecules.展开更多
Metal-organic frameworks(MOFs)would be as one of the highly promising candidates for the electrocatalytic oxidation of small organic molecules and electrochemical sensing due to their adjustable structures and abundan...Metal-organic frameworks(MOFs)would be as one of the highly promising candidates for the electrocatalytic oxidation of small organic molecules and electrochemical sensing due to their adjustable structures and abundant redox-active sites.The development of new chiral MOFs constructed from chiral ligands and the exploration of their applications in electrocatalysis and electrochemical sensing are still relatively lacking.Herein,three new chiral Ni(Ⅱ)-MOFs,namely[Ni_(2)(tda)_(2)(bib)(H_(2)O)_(4)](CTGU-53),[Ni_(2)(tda)_(2)(py)_(2)](CTGU-54)and[Ni_(2)(tda)_(2)(4,4′-bpy)_(2)](CTGU-55)have been prepared with tetrahydrothiazole-2,4-dicarboxylic acid)(H_(2)tda),Ni(NO_(3))_(2) and the auxiliary ligands such as 1,1′-benzene-1,4-diylbis(1H-imidazole(bib),pyridine(py)and 4,4′-bipyridine(4,4′-bpy)under solvothermal condition.The electrocatalytic and electrochemical sensing activities towards alcohol oxidation reaction(AOR)and glucose(Glu)detection of these MOFs were systematically investigated.Notably,CTGU-53 exhibits electrocatalytic performance for methanol oxidation(MOR)and ethanol oxidation(EOR),achieving high peak current densities of 31.02 and 31.88 mA·cm^(−2),and an excellent mass specific peak current of 219.0 and 225.1 mA·mg^(−1),respectively.In contrast,CTGU-55 emerges as a superior non-enzymatic glucose sensor,exhibiting remarkable sensitivity of 2066.1μA·cm^(−2)·mM^(−1),a wide linear range(10−1000μM),and an ultralow detection limit value(LOD=0.09μM,S/N=3),surpassing most reported MOF-based Glu sensors.CTGU-55 also features a fast response time,excellent selectivity against common interferents,and good cyclic stability.This work highlights chiral Ni-MOFs,particularly CTGU-53 and CTGU-55,as highly efficient electrocatalysts for AOR and ultrasensitive electrochemical probes for glucose monitoring,demonstrating significant potential for practical electrochemical applications.展开更多
With the increasing popularity of wearable electronic devices,there is an urgent demand to develop electronic textiles(e-textiles)for device fabrication.Nevertheless,the difficulty in reconciliation between conductivi...With the increasing popularity of wearable electronic devices,there is an urgent demand to develop electronic textiles(e-textiles)for device fabrication.Nevertheless,the difficulty in reconciliation between conductivity and manufacturing costs hinders their large-scale practical applications.Herein,we reported a facile and economic method for preparing conductive e-textiles.Specifically,nonconductive polypropylene(PP)was wrapped by reduced graphene oxide(rGO),followed by the electrodeposition of Ni nanoparticles(NPs).Notably,modulating the sheet size of graphene oxide(GO)resulted in controllable deposition of Ni NPs with adjustable size,allowing for controlled manipulations over the structures,morphologies,and conductivity of the obtained e-textiles,which influenced their performance in electrochemical glucose detection subsequently.The optimal material,denoted as Ni/rGO+(0.2)/PP,exhibited an impressive conductivity of 7.94×10^(4)S·m^(−1).With regard to the excellent conductivity of the as-prepared e-textiles and the high electrocatalytic activity of Ni for glucose oxidation,the asprepared e-textiles were subjected to glucose detection.It was worth emphasizing that the Ni/rGO_(0.2)/PP-based electrode demonstrated promising performance for nonenzymatic/label-free glucose detection,with a detection limit of 0.36μM and a linear response range of 0.5μM to 1 mM.This study paves the way for further development and application prospects of conductive etextiles.展开更多
To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to di...To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy展开更多
基金the Natural Science Foundation of Jiangsu Province (BK2003047)~~
文摘[ Objective] In order to study the anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of EGB fermentation extraction biotransformed by Hericium erinaceus. [ Method ] The free radical scavenging ability and reducing capacity of DPPH as well as inhibitory rate of nonenzymatic glycation reaction were measured targets for comparing changes of anti-oxidation and inhibitory effect on nonenzymatic glycation reaction of fermentation lyophilizer and fermentation extraction before and after EGB fermention adsorbed by AB-8 macroporous resin. The EGB fermention was biotransformed by Hericium erinaceus. [ Result ] After adsorbed by AB-8 macroporous resin, the bioactive matters were concentrated and separated. The free radical scavenging rate, reducing capacity and inhibitory rate of nonenzymatic glycation reaction were increased significantly after adsorbed by AB-8 macroporous resin. [ Conclusion] AB-8 macroporous resin could be used for preliminary concentration of EGB fermentation which was biotransformed by Hericium erinaceus.
基金supported by the University of Engineering and Technology, Lahore, Pakistan
文摘The multiwalled carbon nanotubes thin-film-based electrode was fabricated by electrophoretic deposition and modified with copper （Cu） nanoparticles to fabricate Cu/CNTs nanocomposite sensor for nonenzymatic glucose detection. The expensive glassy carbon electrode was replaced by fluorine-doped tin oxide glass containing CNTs film to confine the Cu nanoparticles growth by electrodeposition through cyclic voltammetry （CV）. The ultraviolet visible and X-ray diffraction analysis revealed the successful deposition of Cu nanoparticles on the CNTs-modified electrode. The atomic force microscopy images confirrqed the morphology of electrodeposited Cu on CNTs film as uniformly dispersed particles. The electrocatalytic activity of electrode to the glucose oxidation was investigated in alkaline medium by CV and amperometric measurements. The fabricated sensor exhibited a fast response time of less than 5 s and the sensitivity of 314 μA rnM^-1 cm^-2 with linear concentration range （0.02-3.0 mM） having detection limit 10.0 μM. Due to simple preparation of sensor, Cu/CNTs nanocomposite electrodes are a suitable candidate for reliable determination of glucose with good stability.
基金supported by the Universities Natural Science Foundation of Jiangsu Province (No. 11KJB480001)Postdoctoral Foundation of Jiangsu Province (No. 1102125C)Highly Qualified Professional Initial Funding of Jiangsu University (No. 10JDG120)
文摘A novel nonenzymatic glucose sensor was successfully fabricated based on the Cu2O polyhedrons covered Cu foil. The Cu2O polyhedrons covered Cu foil was constructed via a facile, low-cost and larger scale producible method. The Cu2O polyhedrons covered Cu foil can be directly used as the working electrode of nonenzymatic glucose sensor, which present good stability and flexibility. The results indicated that the Cu2O polyhedrons modified Cu electrode （Cu2O/Cu electrode） showed high electrocatalytic activity for the oxidation of glucose in alkaline solution. There are two linear regions of glucose concentration for the glucose sensor based on Cu2O/Cu electrode, respectively in 10μmol/L to 0.53 mmol/L （sensitivity： 3029.33 μA （mmol/ L）^-1 cm^-2） and in 0.53-7.53 mmol/L （sensitivity： 728.67 μA （rnmol/L）^-1 cm^-2）.
基金the financial support of the Hong Kong Research Grant Council(14300822)the Chinese University of Hong Kong(CUHK)+1 种基金The TOC figure was created with BioRender.com.the original authors of the images used in the review.
文摘Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displacement(TMSD)and branch migration.With their sensitive and efficient signal amplification capabilities,NDARs have become essential tools for biomarker detection and intracellular imaging.They encompass four primary amplification methods:catalytic hairpin assembly(CHA),hybridization chain reaction(HCR),DNAzyme-based amplification,and entropy-driven circuits(EDC).Based on amplification mechanisms,NDARs can be categorized into three types:stimuli-responsive NDARs,which employ single amplification strategies triggered by specific stimuli like pH,light,or biomolecules;cascade NDARs,which integrate two or more amplification reactions for stepwise signal enhancement;and autocatalytic NDARs,which achieve exponential amplification through self-sustained cycling.These advanced designs progressively improve amplification efficiency,enhance sensitivity,and minimize background noise,enabling precise detection of proteins,viruses,and nucleic acids as well as applications in cancer cell imaging and therapy.Compared with classical NDARs,these approaches significantly reduce signal leakage,offering broader applicability in diagnostics,imaging,and therapeutic contexts.This review summarizes recent advancements,addresses existing challenges,and explores future directions,providing insights into the development and applications of NDARs.
基金funded by the National Key R&D Program of China(2022YFC2104900)National Natural Science Foundation of China(22278183)+2 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-003)Key-Area Research and Development Program of Guangdong Province(2020B020226007)the Fundamental Research Funds for the Central Universities(JUSRP622008).
文摘D-Allulose 3-epimerase(DAEase)is a biocatalyst of concern for D-allulose enzymatic synthesis;however,it exhibits comparatively low thermal stability.To facilitate the directed evolution of DAEase,a nonenzymatic colorimetric assay was developed for high-throughput screening of enhanced DAEase mutants.One desirable mutant,MT4(S38F/F42N/A70P/T119P),was screened based on purifying selection of the randomly muta-genesis library and positive screening of the randomly shuffled library.Compared to the wild-type,the combi-national mutant MT4 had higher catalytic activity(1.23-fold)and showed 5,6.2,and 6.92℃ increases in T_(opt),T_(50),and T_(m) values,respectively.Furthermore,at 60℃,the t_(1/2) value of mutant MT4 was 7.30nullh,exhibiting an 11.4-fold increase in comparison to the wild-type.When the mutant MT4 was used in D-allulose production,the yield reached 28.3%,higher than the 25.1%achieved by the wild-type.Dynamic property and structural change analysis demonstrated that the enhanced properties of mutant MT4 were largely attributed to theβ4-α4 loop rigidification and active-site tunnel entrance constriction.This work expands the industrial application value of DAEase and provides a robust method as the basis for further protein engineering to achieve better performance of this enzyme.
基金supported by the National Natural Science Foundation of China(Grant No.31901249),the Hunan Provincial Natural Science Foundation of China(Grant No.2022JJ30079)the Hunan Provincial Technical Innovation Platform and Talent Program in Science and Technology(Grant No.2020RC3041)the Training Program for Excellent Young Innovators of Changsha(Grant No.kq2106056).
文摘With increasing emphasis on green chemistry,biomass-based materials have attracted increased attention regarding the development of highly efficient functional materials.Herein,a new pore-rich cellulose nanofibril aerogel is utilized as a substrate to integrate highly conductive polypyrrole and active nanoflower-like nickel-cobalt layered double hydroxide through in situ chemical polymerization and electrodeposition.This ternary composite can act as an effective self-supported electrode for the electrocatalytic oxidation of glucose.With the synergistic effect of three heterogeneous components,the electrode achieves outstanding glucose sensing performance,including a high sensitivity(851.4μA·mmol^(−1)·L·cm^(−2)),a short response time(2.2 s),a wide linear range(two stages:0.001−8.145 and 8.145−35.500 mmol·L^(−1)),strong immunity to interference,outstanding intraelectrode and interelectrode reproducibility,a favorable toxicity resistance(Cl^(‒)),and a good long-term stability(maintaining 86.0%of the original value after 30 d).These data are superior to those of some traditional glucose sensors using nonbiomass substrates.When determining the blood glucose level of a human serum,this electrode realizes a high recovery rate of 97.07%–98.89%,validating the potential for highperformance blood glucose sensing.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金The Iranian Nanotechnology Initiative,Research Council of Isfahan University of Technology,and Centre of Excellence in Sensor and Green Chemistry
文摘A nonenzymatic electrochemical sensor for glucose and fructose was fabricated that contained a glassy carbon electrode modified with a copper oxide (CuO)/multiwalled carbon nanotube (MWCNT) nanocomposite. The electrochemical properties of the CuO/MWCNT‐modified glassy carbon electrode were investigated. Two distinguishable anodic peaks were observed around 0.30 and 0.44 V corresponding to the oxidation of glucose and fructose, respectively, at the surface of the modified electrode. The detection limits for glucose and fructose were both 0.04 mmol/L. The sensor was used to simultaneously determine the concentrations of glucose and fructose in hydrolyzed sucrose samples, and to measure glucose in blood serum samples, demonstrating its potential as a nonenzymatic carbohydrate sensor.
基金financially supported by National Natural Science Foundation of China(No.81803403)CAMS Innovation Fund for Medical Sciences(Nos.CIFMS-2022-I2M-JB-011 and CIFMS-2021-12M-1-029).
文摘Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side chains.These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways.Stachbotrydial(2)with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines.In the present work,an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono-and diamines in the fungus Stachybotrys chartarum cultures.In total,24 phenylspirodrimane lactams(1,3-25)including 18 new compounds were synthesized.Among them,stachybocin A(1),a bioactive phenylspirodrimane lactam dimer,was produced with the yield of 18.7 mg/g of cell dry weight.The structures of these compounds were elucidated by extensive spectroscopic data,single-crystal X-ray diffraction(Cu Kα),and calculated electronic circular dichroism(ECD)analyses.Bioassay revealed that compounds 1,17,and 24 displayed significant inhibitory effect on the inactivated state of hNav 1.2 channels with IC_(50) values of 0.22,2.08,and 0.53μmol/L,respectively.In addition,1 showed potent protein tyrosine phosphatase 1B(PTP1B)inhibitory N-methyl-b-aspartate(NMDA)receptor antagonistic,and anti-inflammatory activities.
文摘Racemization of aspartic acid (Asp) residues in proteins plays an important role in the molecular biology of aging. In the widely accepted mechanism of the Asp racemization, a succinimide (SI) intermediate is the species which actually undergo the direct racemization. In the present study, a two-water-assisted mechanism of the SI racemization was computationally investigated using a model compound in which an aminosuccinyl (Asu) residue is capped with acetyl and NMe groups on the N-and C-termini, respectively. The two water molecules catalyze the enolization of the Hα-Cα-C=O portion in the Asu residue by mediating proton relay from the α-carbon atom to the carboxyl oxygen atom. After the enolization, migration of the water molecules and conformational change lead to the mirror image of the initially formed enol two-water complex, and the racemization is completed by the following ketonization. The overall activation barrier (28.2 kcal·mol-1) corresponds to the enolization and ketonization steps, and falls within the available experimental activation energies (21.4-29.0 kcal·mol-1). Therefore, the two-water-assisted mechanism investigated here is plausible for the in vivo and in vitro racemization reactions of the SI intermediates formed in peptides and proteins.
基金supported by the National Key Research and Development Program of China(Nos.2023YFC3503900,2023YFA0914102)National Natural Science Foundation of China(Nos.82325046,82273829,92357305,22377004,22077007)the key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302-2201-17)。
文摘Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study describes the generation of 15 new halogenated angucyclinones through the incorporation of halogen-containing phenylamines into a biosynthetic C-ringcleaved angucyclinone under mild conditions.The newly synthesized compounds feature halogen substituents encompassing all four halogen atoms(F,Cl,Br,I),with some compounds containing multiple halogen types.Structural elucidation was accomplished through ultraviolet(UV),infrared spectroscopy(IR),mass spectrometry(MS),and nuclear magnetic resonance(NMR)spectroscopic analyses,expanding the structural diversity of angucyclinonetype polyketides.Cytotoxicity evaluations revealed that eight compounds demonstrated moderate cytotoxic activities against four human tumor cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.35±0.37 to 16.02±6.60μmol·L-1.These findings highlight the significant potential of combining biosynthetic and chemical approaches in generating bioactive halogenated molecules.
基金the National Natural Science Foundation of China(Nos.22371165 and 22209098)the 111 Project(No.D20015)ITOYMR in the Higher Education Institutions of Hubei Province(No.T201904).
文摘Metal-organic frameworks(MOFs)would be as one of the highly promising candidates for the electrocatalytic oxidation of small organic molecules and electrochemical sensing due to their adjustable structures and abundant redox-active sites.The development of new chiral MOFs constructed from chiral ligands and the exploration of their applications in electrocatalysis and electrochemical sensing are still relatively lacking.Herein,three new chiral Ni(Ⅱ)-MOFs,namely[Ni_(2)(tda)_(2)(bib)(H_(2)O)_(4)](CTGU-53),[Ni_(2)(tda)_(2)(py)_(2)](CTGU-54)and[Ni_(2)(tda)_(2)(4,4′-bpy)_(2)](CTGU-55)have been prepared with tetrahydrothiazole-2,4-dicarboxylic acid)(H_(2)tda),Ni(NO_(3))_(2) and the auxiliary ligands such as 1,1′-benzene-1,4-diylbis(1H-imidazole(bib),pyridine(py)and 4,4′-bipyridine(4,4′-bpy)under solvothermal condition.The electrocatalytic and electrochemical sensing activities towards alcohol oxidation reaction(AOR)and glucose(Glu)detection of these MOFs were systematically investigated.Notably,CTGU-53 exhibits electrocatalytic performance for methanol oxidation(MOR)and ethanol oxidation(EOR),achieving high peak current densities of 31.02 and 31.88 mA·cm^(−2),and an excellent mass specific peak current of 219.0 and 225.1 mA·mg^(−1),respectively.In contrast,CTGU-55 emerges as a superior non-enzymatic glucose sensor,exhibiting remarkable sensitivity of 2066.1μA·cm^(−2)·mM^(−1),a wide linear range(10−1000μM),and an ultralow detection limit value(LOD=0.09μM,S/N=3),surpassing most reported MOF-based Glu sensors.CTGU-55 also features a fast response time,excellent selectivity against common interferents,and good cyclic stability.This work highlights chiral Ni-MOFs,particularly CTGU-53 and CTGU-55,as highly efficient electrocatalysts for AOR and ultrasensitive electrochemical probes for glucose monitoring,demonstrating significant potential for practical electrochemical applications.
基金Sanya Science and Education Innovation Park of Wuhan University of Technology(No.2022KF0013)the Natural Science Foundation of Hainan Province of China(No.623MS068)+1 种基金the PhD Scientific Research and Innovation Foundation of Sanya Yazhou Bay Science and Technology City(No.HSPHDSRF-2023-03-013)the National Natural Science Foundation of China(Nos.22279097 and 62001338).
文摘With the increasing popularity of wearable electronic devices,there is an urgent demand to develop electronic textiles(e-textiles)for device fabrication.Nevertheless,the difficulty in reconciliation between conductivity and manufacturing costs hinders their large-scale practical applications.Herein,we reported a facile and economic method for preparing conductive e-textiles.Specifically,nonconductive polypropylene(PP)was wrapped by reduced graphene oxide(rGO),followed by the electrodeposition of Ni nanoparticles(NPs).Notably,modulating the sheet size of graphene oxide(GO)resulted in controllable deposition of Ni NPs with adjustable size,allowing for controlled manipulations over the structures,morphologies,and conductivity of the obtained e-textiles,which influenced their performance in electrochemical glucose detection subsequently.The optimal material,denoted as Ni/rGO+(0.2)/PP,exhibited an impressive conductivity of 7.94×10^(4)S·m^(−1).With regard to the excellent conductivity of the as-prepared e-textiles and the high electrocatalytic activity of Ni for glucose oxidation,the asprepared e-textiles were subjected to glucose detection.It was worth emphasizing that the Ni/rGO_(0.2)/PP-based electrode demonstrated promising performance for nonenzymatic/label-free glucose detection,with a detection limit of 0.36μM and a linear response range of 0.5μM to 1 mM.This study paves the way for further development and application prospects of conductive etextiles.
文摘To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic nephropathy
