220 results on '"Qingdao National Laboratory for Marine Science and Technology"'
Search Results
2. Intestinal-Target and Glucose-Responsive Smart Hydrogel toward Oral Delivery System of Drug with Improved Insulin Utilization.
- Author
-
Ying R, Wang W, Chen R, Zhou R, and Mao X
- Abstract
An intelligent insulin delivery system targeting intestinal absorption and glucose responsiveness can enhance the bioavailability through oral insulin therapy, offering promising diabetes treatment. In this paper, a glucose and pH dual-response polymer hydrogel using carboxymethyl agarose modified with 3-amino-phenylboronic acid and l-valine (CPL) was developed as an insulin delivery carrier, exhibiting excellent biocompatibility and effective insulin encapsulation. The insulin encapsulated in the hydrogel (Ins-CPL) was released in a controlled manner in response to the in vivo stimulation of blood glucose and pH levels with higher levels of intracellular uptake and utilization of insulin in the intestinal environment simultaneously. Notably, the Ins-CPL hydrogel effectively regulated blood sugar in diabetic rats over a long period by simulating endogenous insulin, responding to changes in plasma pH and glucose levels, and overcoming the intestinal epithelium barrier. This indicates a significant boost in oral insulin bioavailability and broadens its application prospects.
- Published
- 2024
- Full Text
- View/download PDF
3. Chitosan-Based Charge-Controllable Supramolecular Carrier for Universal Immobilization of Enzymes with Different Isoelectric Points.
- Author
-
Wang W, Huang WC, He Y, Zhang Y, and Mao X
- Abstract
Electrostatic adsorption is an enzyme immobilization method that effectively maintains enzyme activity and exhibits considerable binding efficiency. However, enzymes carry different charges at their respective reaction pH levels, which prevents the use of the same carrier to immobilize enzymes with different charges. In this study, we employed a template-mediated polysaccharide-enzyme coupling self-assembly strategy to develop a charge-controllable supramolecular immobilization carrier by regulating the charge properties of carboxymethyl chitosan, enabling the universal immobilization of enzymes with different charge levels across a range of reaction pH values. By using silica nanoparticles of certain sizes as templates, the size of the carrier can be precisely controlled and the hollow network structure formed after removing the template can effectively reduce mass transfer resistance. Trypsin and papain are used as model enzymes, and the experimental results show that the supramolecular self-assembly immobilization strategy does not disrupt the secondary structure of the enzyme molecules. After 2 h of reaction, the enzyme activities of immobilized papain and immobilized trypsin are 13.2% and 7.7% higher than those of the free enzymes, respectively. After 10 consecutive reactions, the enzyme activities of immobilized papain and immobilized trypsin retained 56.3% and 64.3% of their initial values, respectively.
- Published
- 2024
- Full Text
- View/download PDF
4. In Situ Synthesis and Visualization of Membrane SNAP25 Nano-Organization.
- Author
-
Cheng S, Zhang J, Zhang Y, Wang H, and Wang H
- Subjects
- Humans, HEK293 Cells, Cryoelectron Microscopy, Electron Microscope Tomography methods, Synaptosomal-Associated Protein 25 metabolism, Synaptosomal-Associated Protein 25 chemistry, Gold chemistry, Metal Nanoparticles chemistry, Cell Membrane chemistry, Cell Membrane metabolism
- Abstract
Cryo-electron tomography (cryo-ET) can provide insights into the structure and states of natural membrane environments to explore the role of SNARE proteins at membrane fusion and understand the relationship between their subcellular localization/formation and action mechanism. Nevertheless, the identification of individual molecules in crowded and low signal-to-noise ratio membrane environments remains a significant challenge. In this study, cryo-ET is employed to image near-physiological state 293T cell membranes, specifically utilizing in situ synthesized gold nanoparticles (AuNPs) bound with cysteine-rich protein tags to single-molecularly labeled synaptosomal-associated protein 25 (SNAP25) on the membrane surface. The high-resolution images reveal that SNAP25 is predominantly located in regions of high molecular density within the cell membrane and aggregates into smaller clusters, which may increase the fusion efficiency. Remarkably, a zigzag arrangement of SNAP25 is observed on the cell membrane. These findings provide valuable insights into the functional mechanisms of SNARE proteins.
- Published
- 2024
- Full Text
- View/download PDF
5. Structure-Assisted Design of Chitosanase Product Specificity for the Production of High-Degree Polymerization Chitooligosaccharides.
- Author
-
Jia Z, Su H, Zhao Q, Wang S, Sun J, and Mao X
- Subjects
- Substrate Specificity, Archaeal Proteins genetics, Archaeal Proteins metabolism, Archaeal Proteins chemistry, Chitin metabolism, Chitin chemistry, Chitin analogs & derivatives, Kinetics, Oligosaccharides chemistry, Oligosaccharides metabolism, Chitosan chemistry, Chitosan metabolism, Glycoside Hydrolases genetics, Glycoside Hydrolases metabolism, Glycoside Hydrolases chemistry, Mutagenesis, Site-Directed, Polymerization, Methanosarcina enzymology, Methanosarcina genetics, Methanosarcina metabolism, Methanosarcina chemistry
- Abstract
Chitosanases are valuable enzymatic tools in the food industry for converting chitosan into functional chitooligosaccharides (COSs). However, most of the chitosanases extensively characterized produced a low degree of polymerization (DP) COSs (DP = 1-3, LdpCOSs), indicating an imperative for enhancements in the product specificity for the high DP COS (DP >3, HdpCOSs) production. In this study, a chitosanase from Methanosarcina sp. 1.H.T.1A.1 (OUC-CsnA4) was cloned and expressed. Analysis of the enzyme-substrate interactions and the subsite architecture of the OUC-CsnA4 indicated that a Ser49 mutation could modify its interaction pattern with the substrate, potentially enhancing product specificity for producing HdpCOSs. Site-directed mutagenesis provided evidence that the S49I and S49P mutations in OUC-CsnA4 enabled the production of up to 24 and 26% of (GlcN)
5 from chitosan, respectively─the wild-type enzyme was unable to produce detectable levels of (GlcN)5 . These mutations also altered substrate binding preferences, favoring the binding of longer-chain COSs (DP >5) and enhancing (GlcN)5 production. Furthermore, molecular dynamics simulations and molecular docking studies underscored the significance of +2 subsite interactions in determining the (GlcN)4 and (GlcN)5 product specificity. These findings revealed that the positioning and interactions of the reducing end of the substrate within the catalytic cleft are crucial factors influencing the product specificity of chitosanase.- Published
- 2024
- Full Text
- View/download PDF
6. Preservation of Organic Carbon Associated with Iron on Continental Shelves Influenced by Hydrodynamic Processes.
- Author
-
Li H, Lin D, Zhang H, Wang N, Zhou Y, Wu W, Liu J, Che Y, Xia C, Zhu L, Peng C, Liu Q, He Q, and Bao R
- Subjects
- China, Oceans and Seas, Iron chemistry, Carbon chemistry, Hydrodynamics, Geologic Sediments chemistry
- Abstract
Understanding the environmental fate of organic carbon associated with iron (OC-Fe) is critically important for investigating OC preservation in aquatic systems. Here, we first investigate
13 C and14 C isotopes of OC-Fe within grain size-fractionated sediments retrieved from the East China Sea and estimate their sources and reactivities of OC-Fe through isotope-mixing models and thermal pyrolysis approaches in order to reveal the fate of OC-Fe on continental shelves influenced by hydrodynamic processes. Our results show that the OC-Fe proportion in total OC ( fOC-Fe ) in the sortable silt fractions (20-63 μm) is the highest among three grain size fractions, likely suggesting that hydrodynamics may enhance the iron protection on OC. In addition, Δ14 values fall within the range of from -358.73 to -64.03‰, and both ΔOC-Fe values fall within the range of from -358.73 to -64.03‰, and both Δ14 values and ancient OC-Fe% exhibit strong positive linear relationships withOC-Fe values and ancient OC-Fe% exhibit strong positive linear relationships with fOC-Fe . This emphasized that the hydrodynamic processes may cause the ancient OC to be tightly associated with Fe, accompanying OC-Fe aging. Our findings shed new light on the preservation of OC-Fe in marginal seas to advance the recognition of carbon "rusty sinks" in seafloor sediments.- Published
- 2024
- Full Text
- View/download PDF
7. Cryogel with Modular and Clickable Building Blocks: Toward the Ultimate Ideal Macroporous Medium for Bacterial Separation.
- Author
-
Yan X, Wei F, Gou J, Ji M, Hamouda HI, Xue C, and Zheng H
- Subjects
- Animals, Porosity, Milk microbiology, Milk chemistry, Boronic Acids chemistry, Cattle, Methacrylates chemistry, Cryogels chemistry, Staphylococcus aureus isolation & purification, Click Chemistry, Salmonella isolation & purification
- Abstract
The lack of practical platforms for bacterial separation remains a hindrance to the detection of bacteria in complex samples. Herein, a composite cryogel was synthesized by using clickable building blocks and boronic acid for bacterial separation. Macroporous cryogels were synthesized by cryo-gelation polymerization using 2-hydroxyethyl methacrylate and allyl glycidyl ether. The interconnected macroporous architecture enabled high interfering substance tolerance. Nanohybrid nanoparticles were prepared via surface-initiated atom transfer radical polymerization and immobilized onto cryogel by click reaction. Alkyne-tagged boronic acid was conjugated to the composite for specific bacteria binding. The physical and chemical characteristics of the composite cryogel were analyzed systematically. Benefitting from the synergistic, multiple binding sites provided by the silica-assisted polymer, the composite cryogel exhibited excellent affinity toward S. aureus and Salmonella spp. with capacities of 91.6 × 10
7 CFU/g and 241.3 × 107 CFU/g in 0.01 M PBS (pH 8.0), respectively. Bacterial binding can be tuned by variations in pH and temperature and the addition of monosaccharides. The composite was employed to separate S. aureus and Salmonella spp. from spiked tap water, 40% cow milk, and sea cucumber enzymatic hydrolysate, which resulted in high bacteria separation and demonstrated remarkable potential in bacteria separation from food samples.- Published
- 2024
- Full Text
- View/download PDF
8. In Situ Preparation of Star-Shaped Protein-"Smart" Polymer Conjugates with pH and Thermo-Dual Responsibility for Bacterial Separation.
- Author
-
Wei F, Zheng H, Gao C, Tian J, Gou J, Hamouda HI, and Xue C
- Abstract
To achieve effective separation and enrichment of bacteria, a novel synthetic scheme was developed to synthesize star-style boronate-functionalized copolymers with excellent hydrophilicity and temperature and pH responsiveness. A hydrophilic copolymer brush was synthesized by combining surface-initiated atom-transfer radical polymerization with amide reaction using bovine serum albumin as the core. The copolymer brush was further modified by introducing and immobilizing fluorophenylboronic acids through an amide reaction, resulting in the formation of boronate affinity material BSA@poly(NIPAm- co -AGE)@DFFPBA. The morphology and organic content of BSA@poly(NIPAm- co -AGE)@DFFPBA were systematically characterized. The BSA-derived composites demonstrated a strong binding capacity to both Gram-positive and Gram-negative bacteria. The binding capabilities of the affinity composite to Staphylococcus aureus and Salmonella spp. were 195.8 × 10
10 CFU/g and 79.2 × 1010 CFU/g, respectively, which indicates that the novel composite exhibits a high binding capability to bacteria and shows a particularly more significant binding capacity toward Gram-positive bacteria. The bacterial binding of BSA@poly(NIPAm- co -AGE)@DFFPBA can be effectively altered by adjusting the pH and temperature. This study demonstrated that the star-shaped affinity composite had the potential to serve as an affinity material for the rapid separation and enrichment of bacteria in complex samples.- Published
- 2024
- Full Text
- View/download PDF
9. Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.
- Author
-
Dong Q, Yang YH, Lv XJ, Liu JH, and Liu YK
- Abstract
An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K
2 CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.- Published
- 2024
- Full Text
- View/download PDF
10. Switchable CO 2 -Responsive Janus Nanoparticle for Lipase Catalysis in Pickering Emulsion.
- Author
-
Wang W, Zhou R, Di S, Mao X, and Huang WC
- Subjects
- Esterification, Enzyme Stability, Kinetics, Silicon Dioxide chemistry, Catalysis, Hydrolysis, Lipase chemistry, Lipase metabolism, Enzymes, Immobilized chemistry, Enzymes, Immobilized metabolism, Emulsions chemistry, Nanoparticles chemistry, Carbon Dioxide chemistry, Carbon Dioxide metabolism, Biocatalysis
- Abstract
The use of convertible immobilized enzyme carriers is crucial for biphasic catalytic reactions conducted in Pickering emulsions. However, the intense mechanical forces during the conversion process lead to enzyme leakage, affecting the stability of the immobilized enzymes. In this study, a CO
2 -responsive switchable Janus (CrSJ) nanoparticle (NP) was developed using silica NP, with one side featuring aldehyde groups and the other side adsorbing N , N -dimethyldodecylamine. A switchable Pickering emulsion catalytic system for biphasic interface reactions was prepared by covalently immobilizing lipase onto the CrSJ NPs. The CO2 -responsive nature of the CrSJ NPs allowed for rapid conversion of the Pickering emulsion, and covalent immobilization substantially reduced lipase leakage while enhancing the stability of the immobilization during the conversion process. Impressively, after repeated transformations, the Pickering emulsion still maintains its original structure. Following 10 consecutive cycles of esterification and hydrolysis reactions, the immobilized enzyme's activity remains at 77.7 and 79.5% of its initial activity, respectively. The Km values were 1.2 and 1.6 times that of the free enzyme in esterification and hydrolysis reactions, respectively.Vmax values were 1.2 and 1.6 times that of the free enzyme in esterification and hydrolysis reactions, respectively.- Published
- 2024
- Full Text
- View/download PDF
11. Characterization and Hydrolysis Mechanism Analysis of a Cold-Adapted Trypsin-Like Protease from Antarctic Krill.
- Author
-
Xin S, Zhang H, Sun J, and Mao X
- Subjects
- Animals, Hydrolysis, Substrate Specificity, Amino Acid Sequence, Tandem Mass Spectrometry, Enzyme Stability, Antarctic Regions, Euphausiacea chemistry, Euphausiacea enzymology, Euphausiacea genetics, Euphausiacea metabolism, Cold Temperature, Trypsin metabolism, Trypsin chemistry, Trypsin genetics
- Abstract
Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature food processing. In this paper, we attempted to characterize cold-adapted proteases from Antarctic krill. Antarctic krill possesses an extremely active autolytic enzyme system in their bodies, and the production of peptides and free amino acids accompanies the rapid breakdown of muscle proteins following the death. The crucial role of trypsin in this process is recognized. A cold-adapted trypsin named OUC-Pp-20 from Antarctic krill genome was cloned and expressed in Pichia pastoris . Recombinant trypsin is a monomeric protein of 26.8 ± 1.0 kDa with optimum reaction temperature at 25 °C. In addition, the catalytic specificity of OUC-Pp-20 was assessed by identifying its hydrolysis sites through LC-MS/MS. OUC-Pp-20 appeared to prefer Gln and Asn at the P1 position, which is an amino acid with an amide group in its side chain. Hydrolysis reactions on milk and shrimp meat revealed that it can effectively degrade allergenic components in milk and arginine kinase in shrimp meat. These findings update the current knowledge of cold-adapted trypsin and demonstrate the potential application of OUC-Pp-20 in low temperature food processing.
- Published
- 2024
- Full Text
- View/download PDF
12. Bioconversion of α-Chitin by a Lytic Polysaccharide Monooxygenase Os LPMO10A Coupled with Chitinases and the Synergistic Mechanism Analysis.
- Author
-
Zhao H, Su H, Sun J, Dong H, and Mao X
- Subjects
- Mixed Function Oxygenases metabolism, Polysaccharides metabolism, Serratia marcescens, Chitin chemistry, Chitinases chemistry
- Abstract
The whole enzymatic conversion of chitin is a green and promising alternative to current strategies, which are based on lytic polysaccharide monooxygenases (LPMOs) and chitinases. However, the lack of LPMOs with high activity toward α-chitin limits the efficient bioconversion of α-chitin. Herein, we characterized a high chitin-active LPMO from Oceanobacillus sp. J11TS1 ( Os LPMO10A), which could promote the decrystallization of the α-chitin surface. Furthermore, when coupled with Os LPMO10A, the conversion rate of α-chitin to N -acetyl chitobiose [(GlcNAc)
2 ] by three chitinases ( Serratia marcescens , ChiA, -B, and -C) reached 30.86%, which was 2.03-folds that without the addition of Os LPMO10A. Moreover, the results of synergistic reactions indicated that Os LPMO10A and chitinases promoted the degradation of α-chitin each other mainly on the surface. To the best of our knowledge, this study achieved the highest yield of N -acetyl chitooligosaccharides ( N -acetyl COSs) among reported LPMOs-driven bioconversion systems, which could be regarded as a promising candidate for α-chitin bioconversion.- Published
- 2024
- Full Text
- View/download PDF
13. Rapid FRET Assay for the Early Detection of Alpha-Synuclein Aggregation in Parkinson's Disease.
- Author
-
Yu H, Feng R, Chen F, Wu Z, Li D, and Qiu X
- Subjects
- Humans, alpha-Synuclein metabolism, Fluorescence Resonance Energy Transfer, Parkinson Disease metabolism
- Abstract
Alpha-synuclein (α-Syn) is a key protein of Parkinson's disease (PD). Oligomers formed by misfolding and aggregation of α-Syn can cause many pathological phenomena and aggravate the development of PD. Therefore, sensitive and accurate detection of oligomers is essential to understanding the pathology of PD and beneficial to screening and developing new drugs against PD. Here, we demonstrated a simple and sensitive method to detect the early aggregation of α-Syn via Förster resonance energy transfer (FRET) technology. We performed systematic investigations of the FRET sensitizations, efficiencies, and donor-to-acceptor distances during α-Syn aggregation, which was proved to be more sensitive to reflect small distance changes in the early stage of α-Syn aggregation, especially for α-Syn oligomers. The FRET assays were also applied to study the influence of Ser129 phosphorylation (pS129) on the aggregation rate of α-Syn. Our results showed that pS129 modification promotes α-Syn aggregation and enhances the ability of preformed fibrils to induce monomer aggregation. pS129 also increased the cytotoxicity of α-Syn. These results are of great significance for a better understanding of the pathological mechanisms of PD and future PD drug development.
- Published
- 2024
- Full Text
- View/download PDF
14. Characterization of a Novel Antimicrobial Peptide Bacipeptin against Foodborne Pathogens.
- Author
-
Wei X, Hu Y, Sun C, and Wu S
- Subjects
- Staphylococcus aureus, Antimicrobial Peptides, Cell Wall, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Methicillin-Resistant Staphylococcus aureus, Anti-Infective Agents pharmacology
- Abstract
The increasing emergence of multidrug-resistant pathogens and development of biopreservatives in food industries has increased the demand of novel and safe antimicrobial agents. In this study, a marine bacterial strain Bacillus licheniformis M1 was isolated and exhibited obvious antimicrobial activities against foodborne pathogens, especially against methicillin-resistant Staphylococcus aureus . The antimicrobial agent was purified and identified as a novel antimicrobial peptide, which was designated as bacipeptin, and the corresponding mechanism was further investigated by electron microscopy observation and transcriptomic analysis with biochemical validation. The results showed that bacipeptin could reduce the virulence of methicillin-resistant Staphylococcus aureus and exerted its antimicrobial activity by interfering with histidine metabolism, inducing the accumulation of reactive oxygen species and down-regulating genes related to Na
+ /H+ antiporter and the cell wall, thus causing damage to the cell wall and membrane. Overall, our study provides a novel natural product against foodborne pathogens and discloses the corresponding action mechanism.- Published
- 2024
- Full Text
- View/download PDF
15. Desymmetric [3+3] Cyclization of p -Quinamines for the Synthesis of 1,2,4-Oxadiazines and Hydroquinoxalines.
- Author
-
Wang X and Ren W
- Abstract
General and efficient strategies for highly diastereoselective synthesis of divergent heterocyclic scaffolds through desymmetric [3+3] cycloaddition of p -quinamines with 1,3-dipole surrogates hydroximoyl halides and α-halohydroxamates have been developed. This synthetic protocol provided a variety of heterocyclic architectures containing 1,2,4-oxadiazine and hydroquinoxaline skeletons in good yields with a wide substrate scope.
- Published
- 2024
- Full Text
- View/download PDF
16. Characterization of a GH20 β- N -Acetylhexosaminidase from Flavobacterium algicola Suitable to Synthesize Lacto- N -triose II.
- Author
-
Li C, Cao Z, Jiang H, Secundo F, and Mao X
- Subjects
- Humans, Powders, Oligosaccharides chemistry, Acetylglucosaminidase, beta-N-Acetylhexosaminidases chemistry, Trisaccharides, Flavobacterium
- Abstract
β- N -Acetylhexosaminidases have attracted much attention in the enzymatic synthesis of lacto- N -triose II (LNT2) as a backbone precursor of human milk oligosaccharides (HMOs). In this study, a novel glycoside hydrolase (GH) 20 family β- N -acetylhexosaminidase, FlaNag2353, from Flavobacterium algicola was biochemically characterized and applied to synthesize LNT2. FlaNag2353 displayed optimal activity to p -nitrophenyl N -acetyl-β-d-glucosaminide ( p NP-GlcNAc) at 40 °C and pH 8.0. In addition to its excellent hydrolysis activity toward p NP-GlcNAc and chitooligosaccharides, FlaNag2353 showed trans-glycosylation activity. Under conditions of pH 9.0 and 55 °C for 2 h and utilizing 200 mM lactose and 10 mM p NP-GlcNAc, FlaNag2353 synthesized LNT2 with a conversion ratio of 4.15% calculated from p NP-GlcNAc. Moreover, when applied to LNT2 synthesis with 10 mM p NP-GlcNAc and 9.7% (w/v) industrial waste whey powder, FlaNag2353 achieved a conversion ratio of 2.39%. This study has significant implications for broadening the applications of GH20 β- N -acetylhexosaminidases and promoting the high-value utilization of whey powder.
- Published
- 2024
- Full Text
- View/download PDF
17. Fucoxanthin Alleviates Dextran Sulfate Sodium-Induced Colitis and Gut Microbiota Dysbiosis in Mice.
- Author
-
Yang YH, Chen C, Zheng Y, Wu ZJ, Zhou MQ, Liu XY, Miyashita K, Duan DL, and Du L
- Subjects
- Mice, Animals, Dextran Sulfate adverse effects, Dysbiosis chemically induced, Dysbiosis drug therapy, Colon metabolism, Mice, Inbred C57BL, Disease Models, Animal, Gastrointestinal Microbiome, Colitis chemically induced, Colitis drug therapy, Colitis metabolism, Xanthophylls
- Abstract
The purpose of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on dextran sulfate sodium (DSS)-induced colitis in mice. The present data demonstrated that oral administration of Fx (50 and 200 mg/kg body weight/day) for 36 days significantly alleviated the severity of colitis in DSS-treated mice, as evidenced by attenuating body weight loss, bloody stool, diarrhea, shortened colon length, colonic epithelium distortion, a thin mucus layer, goblet cell depletion, damaged crypts, and extensive infiltration of inflammatory cells in the colonic mucosa. Additionally, Fx notably relieved DSS-induced intestinal epithelial barrier dysfunction via maintaining the tight junction function and preventing excessive apoptosis of colonic epithelial cells. Moreover, Fx effectively diminished colonic inflammation and oxidative stress in DSS-treated mice, and its mechanisms might be due to blunting the activation of NF-κB and NLRP3 inflammasome signaling pathways. Furthermore, Fx also modulates DSS-induced gut microbiota dysbiosis via recovering the richness and diversity of gut microbiota and reshaping the structure of gut microbiota, such as increasing the Firmicutes and Bacteroidota (F/B) ratio and elevating the relative abundance of some potential beneficial bacteria, including Lactobacillaceae and Lachnospiraceae . Overall, Fx might be developed as a promising functional ingredient to prevent colitis and maintain intestinal homeostasis.
- Published
- 2024
- Full Text
- View/download PDF
18. Dual Antagonism of α9α10 nAChR and GABA B Receptor-Coupled Ca V 2.2 Channels by an Analgesic αO-Conotoxin Analogue.
- Author
-
Li X, Tae HS, Chen S, Yousuf A, Huang L, Zhang J, Jiang T, Adams DJ, and Yu R
- Subjects
- Rats, Humans, Animals, Receptors, GABA-B metabolism, Analgesics pharmacology, Analgesics therapeutic use, Analgesics chemistry, Pain drug therapy, gamma-Aminobutyric Acid, Nicotinic Antagonists pharmacology, Nicotinic Antagonists chemistry, Conotoxins chemistry, Analgesics, Non-Narcotic, Receptors, Nicotinic metabolism
- Abstract
Pain severely affects the physical and mental health of patients. The need to develop nonopioid analgesic drugs to meet medical demands is urgent. In this study, we designed a truncated analogue of αO-conotoxin, named GeX-2, based on disulfide-bond deletion and sequence truncation. GeX-2 retained the potency of its parent peptide at the human α9α10 nAChR and exhibited potent inhibitory activity at Ca
V 2.2 channels via activation of the GABAB receptor (GABAB R). Importantly, GeX-2 significantly alleviated pain in the rat model of chronic constriction injury. The dual inhibition of GeX-2 at both α9α10 nAChRs and CaV 2.2 channels is speculated to synergistically mediate the potent analgesic effects. Results from site-directed mutagenesis assay and computational modeling suggest that GeX-2 preferentially interacts with the α10(+)α10(-) binding site of α9α10 nAChR and favorably binds to the top region of the GABAB R2 subunit. The study offers vital insights into the molecular action mechanism of GeX-2, demonstrating its potential as a novel nonopioid analgesic.- Published
- 2024
- Full Text
- View/download PDF
19. Organocatalyzed Enantioselective [2 + 2] Cycloaddition of C , N -Cyclic Ketimines and Allenoates.
- Author
-
Liu X, Zhu F, Ajitha MJ, Zhang Y, Huang KW, Li D, and Wang
- Abstract
We report a novel enantioselective and regioselective [2 + 2] cycloaddition of allenoate and C , N -cyclic ketimine catalyzed by a quinidine derivative. The methodology enables the synthesis of fused tricyclic azetidines with a quaternary stereogenic center exhibiting high enantioselectivities. The broad range of substrates demonstrates the generality of the protocol, and the resulting functional products can be easily converted to a variety of valuable synthons. To elucidate the plausible reaction mechanism and how the catalyst affects absolute stereocontrol over the products, we conducted the corresponding density functional theory (DFT) calculations.
- Published
- 2024
- Full Text
- View/download PDF
20. High-Yield Synthesis of Phosphatidylserine in a Well-Designed Mixed Micellar System.
- Author
-
Yin C, Sun J, Guo W, Xue Y, Zhang H, and Mao X
- Subjects
- Phosphatidylserines, Phospholipids, Biocatalysis, Solvents, Micelles, Phospholipase D metabolism
- Abstract
A sustainable enzymatic system is essential for efficient phosphatidylserine (PS) synthesis in industrial production. Conventional biphasic systems face challenges such as excessive organic solvent usage, enzyme-intensive processes, and increased costs. This study introduces a novel approach using chitin nanofibrils (ChNFs) as an immobilization material for phospholipase D (PLD) in a mixed micellar system stabilized by the food-grade emulsifier sodium deoxycholate (SDC). The immobilized enzyme, ChNF-chiA1, was quickly prepared in a one-step process, eliminating the need for purification. By optimizing the reaction conditions, including l-Ser concentration (1.0 M), SDC concentration (10 mM), reaction time (8 h), and enzyme dosage (1.0 U), a remarkable PS yield of 96.74% was achieved in the solvent-free mixed micellar system. The catalytic efficiency of ChNF-chiA1 surpassed that of the free PLD-chiA1 biphasic system by 6.0-fold. This innovative and green biocatalytic technology offers a reusable solution for the high-value enzymatic synthesis of phospholipids, providing a promising avenue for industrial applications.
- Published
- 2024
- Full Text
- View/download PDF
21. Robust Potentiometric Microelectrodes for In Situ Sensing of Ion Fluxes with High Sensitivity.
- Author
-
Li Y, Zhu X, Ding J, and Qin W
- Abstract
Simple, reproducible, and reliable preparation of robust potentiometric microelectrodes is both challenging and of great importance for noninvasive real-time ion sensing. Herein, we report a simple strategy for the large-scale synthesis of nickel cobalt sulfide (NiCo
2 S4 ) nanowire arrays grown on carbon fibers for potentiometric microelectrodes. The highly uniform NiCo2 S4 nanowire array serving as a transduction layer can provide a high capillary pressure and viscous resistance for loading the ion sensing membrane and exhibit a large redox capacitance for improving the stability. An all-solid-state lead-selective microelectrode, which presents a detection limit of 2.5 × 10-8 M in the simulated soil solution, was designed as a model for noninvasive, in situ , and real-time detection of ion fluxes near the rice root surface. Importantly, the microsensor enables sensitive detection of trace-level ion-fluxes. This work provides a simple yet general strategy for designing potentiometric microelectrodes.- Published
- 2023
- Full Text
- View/download PDF
22. Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis.
- Author
-
Teng Z, Yang J, Chen X, and Liu Y
- Subjects
- Humans, Administration, Intranasal, Nasal Mucosa, Nasal Cavity, Ketotifen therapeutic use, Nanomedicine, Rhinitis, Allergic drug therapy
- Abstract
Intranasal administration has been widely explored as a potential treatment for allergic rhinitis, and improving intranasal penetration and retention of drugs is a challenging requirement to further improve efficacy. Delivery strategies of nanocarriers that enhance mucosal adhesion or mucus penetration have been proposed to improve nasal drug delivery; however, delivery efficiency remains limited by excessive pulmonary deposition and nonspecific cell phagocytosis. In this work, a "nasal in situ assembly" strategy was presented to construct intranasal morphology transformation nanomedicines with enhanced effective drug concentration for long-term intervention of allergic rhinitis. The polymer-polypeptide nanomedicine (PHCK) with a CCR3 antagonistic peptide (C) and a pH-responsive polyethylene glycol (H) was developed, encapsulating ketotifen (KT). PHCK nanoparticles displayed nasal mucosa permeability and transformed to nanofibers in the acidic environment of the nasal cavity, realizing responsive burst release of KT simultaneously. The fibrotic reassembly reduced the cellular internalization of nanomedicine and increased the CCR3 blockade on the eosinophil (EOS) membranes. Both in vitro and in vivo data indicated that PHCK achieved improved drug accumulation and retention in the nasal cavity and decreased pulmonary deposition, then effectively inhibited mast cell degranulation and EOS chemotaxis. This study demonstrates that the "nasal in situ assembly" strategy can improve drug delivery efficiency upon nasal responsive morphologic transformation, providing exploratory perspectives for nasal delivery platforms establishment and boosting therapeutic effect of allergic rhinitis.
- Published
- 2023
- Full Text
- View/download PDF
23. Organocatalytic Enantioselective Functionalization of Cyclic α-Hydroxyamides: Access to Chiral Cyclic Imides and Azapolycyclic Compounds.
- Author
-
Zhang XQ, Ma YR, and Liu YK
- Abstract
A highly efficient enantioselective enamine-catalyzed asymmetric conjugate addition has been developed to directly convert unfunctionalized cyclic α-hydroxyamides into chiral cyclic α-hydroxyamides by reacting with vinyl sulfones, which could be used as versatile azacyclic synthons in the following sequences: (1) as the precursors of cyclic N -acyliminium ions to prepare natural productlike chiral azapolycyclic compounds under acidic conditions and (2) to construct chiral cyclic imides bearing unilateral substituents via oxidation reaction-induced formal desymmetrization.
- Published
- 2023
- Full Text
- View/download PDF
24. Near-Infrared Laser Irradiation-Modulated High-Temperature Solid-Contact Ion-Selective Electrodes: Potentiometric Detection of Ca 2+ in Seawater.
- Author
-
Guo Y, Yin T, Ding J, and Qin W
- Subjects
- Potentiometry, Temperature, Seawater, Infrared Rays, Ion-Selective Electrodes, Carbon
- Abstract
The high-temperature potentiometry operated by nonisothermal heating is a promising way to break through the traditional potentiometric responses of ion-selective electrodes (ISEs) at room temperature. Herein, a locally heated strategy through near-infrared region (NIR) laser irradiation upon the photothermal mesoporous carbon material placed between the ion-selective membrane and the glassy carbon substrate is introduced to obtain the high-temperature potentiometric performance of a solid-contact Ca
2+ -ISE for detection of Ca2+ in seawater. Based on the light-to-heat conversion of the mesoporous carbon-based solid contact, the temperature of the solid-contact Ca2+ -ISE upon continuous NIR laser irradiation can be increased from room temperature to 60-70 °C, and the slope of the electrode is promoted up to about 30% according to the thermodynamic steady-state potentiometric response. The pulsed potentiometric response of the solid-contact Ca2+ -ISE upon a pulsed NIR laser irradiation of 5 s also shows a linear change as a function of Ca2+ activities, and the improved slope from 27.1 ± 0.6 to 38.1 ± 0.9 mV/dec can be obtained under dual control of the temperature of the electrode and the transient current induced by the pulsed NIR laser irradiation. As compared to the traditional potentiometric measurement under zero-current conditions at room temperature, the NIR laser-modulated high-temperature potentiometric response provides an alternative way for measurement of the solid-contact ISEs.- Published
- 2023
- Full Text
- View/download PDF
25. Preparation of a Dual-Functional Sulfated Galactofucan Polysaccharide/Poly(vinyl alcohol) Hydrogel to Promote Macrophage Recruitment and Angiogenic Potential in Diabetic Wound Healing.
- Author
-
Liu Y, Deng Z, Zhang J, Wu Y, Wu N, Geng L, Yue Y, Zhang Q, and Wang J
- Subjects
- Mice, Animals, Humans, Wound Healing, Polyvinyl Alcohol pharmacology, Polyvinyl Alcohol chemistry, Macrophages, Intercellular Signaling Peptides and Proteins, Hydrogels pharmacology, Hydrogels chemistry, Diabetes Mellitus
- Abstract
A diabetic foot ulcer is a common high-risk complication in diabetic patients, but there is still no universal dressing for clinical treatment. In this study, a novel dual-functional sulfated galactofucan polysaccharide/poly(vinyl alcohol) hydrogel (DPH20) is developed during freeze-thaw cycles. Experimental results indicated that DPH20 had a high specific surface area, a dense porous structure, and a good swelling property, which could effectively adsorb the exudates and keep the wound moist. Furthermore, DPH20 exhibited remarkably recruited macrophage capability and accelerated the inflammation stage by improving the expression of the mRNA of CCL2, CCR2 , and CCL22 in macrophages. DPH20 could promote cell migration and growth factor release to accelerate tube formation under hyperglycemic conditions in cell models of L929s and HUEVCs, respectively. Significantly, DPH20 accelerates the reconstruction of the full-thickness skin wound by accelerating the recruitment of macrophages, promoting angiogenesis, and releasing the growth factor in the diabetic mouse model. Collectively, DPH20 is a promising multifunctional dressing to reshape the damaged tissue environment and accelerate wound healing. This study provides an efficient strategy to repair and regenerate diabetic skin ulcers.
- Published
- 2023
- Full Text
- View/download PDF
26. Functional Proteomics Analysis of Norfloxacin-Resistant Edwardsiella tarda .
- Author
-
Wu JH, Li DL, Tan XH, Chen XW, Liu YL, Munang'andu HM, and Peng B
- Subjects
- Humans, Animals, Edwardsiella tarda metabolism, Proteomics, Siderophores metabolism, Anti-Bacterial Agents pharmacology, Norfloxacin pharmacology, Norfloxacin metabolism, Fish Diseases microbiology
- Abstract
Multidrug-resistant Edwardsiella tarda threatens both sustainable aquaculture and human health, but the control measure is still lacking. In this study, we adopted functional proteomics to investigate the molecular mechanism underlying norfloxacin (NOR) resistance in E. tarda . We found that E. tarda had a global proteomic shift upon acquisition of NOR resistance, featured with increased expression of siderophore biosynthesis and Fe
3+ -hydroxamate transport. Thus, either inhibition of siderophore biosynthesis with salicyl-AMS or treatment with another antibiotic, kitasamycin (Kit), which was uptake through Fe3+ -hydroxamate transport, enhanced NOR killing of NOR-resistant E. tarda both in vivo and in vitro . Moreover, the combination of NOR, salicyl-AMS, and Kit had the highest efficacy in promoting the killing effects of NOR than any drug alone. Such synergistic effect not only confirmed in vitro and in vivo bacterial killing assays but also applicable to other clinic E. tarda isolates. Thus, our data suggest a proteomic-based approach to identify potential targets to enhance antibiotic killing and propose an alternative way to control infection of multidrug-resistant E. tarda .- Published
- 2023
- Full Text
- View/download PDF
27. Engineering Cyanobacterial Cell Factories for Photosynthetic Production of Fructose.
- Author
-
Sun J, Zhang Z, Zhang S, Dan Y, Sun H, Wu Y, Luan G, and Lu X
- Subjects
- Photosynthesis, Metabolic Engineering, Carbohydrate Metabolism, Sucrose metabolism, Carbon Dioxide metabolism, Fructose metabolism, Synechococcus genetics, Synechococcus metabolism
- Abstract
Fructose is an important monosaccharide product widely applied in the food, medicine, and chemical industries. Currently, fructose is mainly manufactured with plant biomass-sourced polysaccharides through multiple steps of digestion, conversion, separation, and purification. The development of cyanobacterial metabolic engineering provides an attractive alternative route for the one-step direct production of fructose utilizing carbon dioxide and solar energy. In this work, we developed a paradigm for engineering cyanobacterial chassis cells into efficient cell factories for the photosynthetic production of fructose. In a representative cyanobacterial strain, Synechococcus elongatus PCC 7942, knockout of fructokinase effectively activated the synthesis and secretion of fructose in hypersaline conditions, independent of any heterologous transporters. The native sucrose synthesis pathway was identified as playing a primary role in fructose synthesis. Through combinatory optimizations on the levels of metabolism, physiology, and cultivation, the fructose yield of the Synechococcus cell factories was stepwise improved to 3.9 g/L. Such a paradigm was also adopted to engineer another Synechococcus strain, the marine species Synechococcus sp. PCC 7002, and facilitated an even higher fructose yield of over 6 g/L. Finally, the fructose synthesized and secreted by the cyanobacterial photosynthetic cell factories was successfully extracted and prepared from the culture broth in the form of products with 86% purity through multistep separation-purification operations. This work demonstrated a paradigm for systematically engineering cyanobacteria for photosynthetic production of desired metabolites, and it also confirmed the feasibility and potential of cyanobacterial photosynthetic biomanufacturing as a simple and efficient route for fructose production.
- Published
- 2023
- Full Text
- View/download PDF
28. Novel Sulfonylurea-Based NLRP3 Inflammasome Inhibitor for Efficient Treatment of Nonalcoholic Steatohepatitis, Endotoxic Shock, and Colitis.
- Author
-
Li Z, Chen Y, Jiang X, Lu P, Wang C, Li Z, Yu X, Yang Z, Ma S, Du S, Tai Z, Li X, Zhang S, Jiang Y, and Qin C
- Subjects
- Mice, Animals, Humans, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Sulfones pharmacology, Sulfonylurea Compounds therapeutic use, Mice, Inbred C57BL, Furans pharmacology, Furans therapeutic use, Non-alcoholic Fatty Liver Disease drug therapy, Shock, Septic drug therapy, Colitis drug therapy
- Abstract
The NLRP3 inflammasome is a critical component of innate immunity involved in the pathophysiology of various inflammatory diseases. In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors based on MCC950. Specifically, we optimized the furan moiety, which is considered to be potentially associated with drug-induced liver injury. The representative inhibitor N14 , 4-(2-(dimethylamino)ethyl)- N -((1,2,3,5,6,7-hexahydro- s -indacen-4-yl)carbamoyl)benzenesulfonamide, not only maintains the NLRP3 inhibitory activity of MCC950 with IC
50 of 25 nM but also demonstrates improved tolerability in human hepatic cells line and mouse primary hepatocytes. In addition, N14 exhibits superior pharmacokinetic properties, with an oral bioavailability of 85.2%. In vivo studies demonstrate that N14 is more effective than MCC950 in multiple NLRP3-related animal model diseases, including nonalcoholic steatohepatitis, lethal septic shock, and colitis. Our research has provided a lead compound that directly targets the NLRP3 inflammasome and can be developed as a novel therapeutic candidate for NLRP3-driven diseases.- Published
- 2023
- Full Text
- View/download PDF
29. Metabolic Engineering of Yarrowia lipolytica for Zeaxanthin Production.
- Author
-
Zhang G, Chen J, Wang Y, Liu Z, and Mao X
- Subjects
- beta Carotene, Zeaxanthins, Carotenoids, Metabolic Engineering, Yarrowia genetics
- Abstract
Zeaxanthin is a carotenoid, a dihydroxy derivative of β-carotene. Zeaxanthin has antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. In this study, Yarrowia lipolytica was used as a host for the efficient production of zeaxanthin. The strain Y. lipolytica PO1h was used to construct the following engineered strains for carotenoid production since it produced the highest β-carotene among the Y. lipolytica PO1h- and Y. lipolytica PEX17-HA-derived strains. By regulating the key nodes on the carotenoid pathway through wild and mutant enzyme comparison and successive modular assembly, the β-carotene concentration was improved from 19.9 to 422.0 mg/L. To provide more precursor mevalonate, heterologous genes mvaE and mvaS
MT was then transferred, resulting in a yield of zeaxanthin of 326.5 mg/L. The oxidoreductase RFNR1 and CrtZ were then used to further enhance zeaxanthin production, and the yield of zeaxanthin was up to 775.3 mg/L in YPD shake flask.crtZ was then transferred, resulting in a yield of zeaxanthin of 326.5 mg/L. The oxidoreductase RFNR1 and CrtZ were then used to further enhance zeaxanthin production, and the yield of zeaxanthin was up to 775.3 mg/L in YPD shake flask.- Published
- 2023
- Full Text
- View/download PDF
30. Aspertides A-E: Antimicrobial Pentadepsipeptides with a Unique p -Methoxycinnamoyl Amide Group from the Marine Isolates Aspergillus tamarii MA-21 and Aspergillus insuetus SD-512.
- Author
-
Chi LP, Liu D, Li XM, Wan Y, Wang BG, and Li X
- Subjects
- Amides, Aspergillus, Anti-Infective Agents pharmacology
- Abstract
Marine fungus-derived natural products are an important source of antimicrobial compounds against marine aquatic pathogens. Here, we describe the isolation and characterization of five new pentadepsipeptides, aspertides A-E ( 1 - 5 ), containing a unique p -methoxycinnamoyl amide group, from the marine fungi Aspergillus tamarii MA-21 and Aspergillus insuetus SD-512. Among them, aspertides B-E ( 2 - 5 ) also possessed uncommon amino acid residues, such as 3-hydroxyproline, 2,3-dihydroxyproline, or pipecolinic acid. The structures of these compounds were elucidated on the basis of NMR and mass spectroscopic analyses. The absolute configurations of them were established by chiral HPLC analyses of the acidic hydrolysates and NMR calculations with DP4+ probability analysis. In bio-activity assays, compounds 4 and 5 exhibited antibacterial activities against aquatic-pathogenic bacteria, including Edwardsiella tarda , Vibrio alginolyticus , Vibrio anguillarum , Vibrio vulnificus, and Staphylococcus aureus, with MIC values of 8-32 μg/mL.
- Published
- 2023
- Full Text
- View/download PDF
31. Photothermal and Acid-Responsive Fucoidan-CuS Bubble Pump Microneedles for Combined CDT/PTT/CT Treatment of Melanoma.
- Author
-
Tao J, Wang B, Dong Y, Chen X, Li S, Jiang T, and Zhao X
- Subjects
- Copper Sulfate chemistry, Photothermal Therapy, Doxorubicin therapeutic use, Antibiotics, Antineoplastic therapeutic use, Combined Modality Therapy, Male, Animals, Mice, Cell Line, Tumor, Mice, Inbred C57BL, Melanoma therapy
- Abstract
Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO
3 ) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO2 bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H2 O2 ) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.- Published
- 2023
- Full Text
- View/download PDF
32. Phosphine-Catalyzed Allylic Alkylation of (Hetero)Aryl Alkynes with Pronucleophiles: Concise Total Synthesis of (±)-Esermethole.
- Author
-
He N, Zhang J, Miao X, Li D, and Wang
- Abstract
Allylic alkylations are valuable in the construction of versatile carbon-carbon bonds, which are mostly catalyzed by noble transition metals with additional waste byproduct generation. Here, we present the first organophosphine-catalyzed allylic alkylation of (hetero)aryl alkynes with various carbo-nucleophiles. The methodology is highly atom economical and compatible with a wide substrate scope (more than 38 examples). Moreover, the reaction could be easily scaled up, and deuterium labeling experiments have been conducted to elucidate the plausible mechanism. Finally, the protocol has been utilized to achieve the concise total synthesis of natural product (±)-esermethole.
- Published
- 2023
- Full Text
- View/download PDF
33. Brønsted-Acid-Catalyzed In Situ Formation of Acyclic Tertiary Enamides and Its Application to the Preparation of Diverse Nitrogen-Containing Heterocyclic Compounds.
- Author
-
Ma YR, Lv XJ, Dong Q, Ming YC, and Liu YK
- Abstract
A Brønsted acid-catalyzed cascade process, involving in situ formation of acyclic tertiary enamides and intramolecular Michael reaction, is developed for the synthesis of functionalized cyclic tertiary enamides. Based on the dual reactivities of the enamide moiety, several reaction sequences were realized by using rationally designed substrates, leading to biologically relevant nitrogen-containing heterocyclic compounds with diverse structural skeletons in a concise and diastereocontrolled manner.
- Published
- 2023
- Full Text
- View/download PDF
34. Chitosan Thermosensitive Hydrogel Based on DNA Damage Repair Inhibition and Mild Photothermal Therapy for Enhanced Antitumor Treatment.
- Author
-
Yu Y, Wang T, Meng X, Jiang T, and Zhao X
- Subjects
- Humans, Hydrogels pharmacology, Gold, Photothermal Therapy, DNA Damage, Cell Line, Tumor, Chitosan, Metal Nanoparticles, Neoplasms
- Abstract
The DNA damage repair of tumor cells limits the effect of photothermal therapy (PTT), and high temperatures induced by PTT can damage adjacent normal tissues. To overcome these limitations, we developed a novel composite hydrogel (OLA-Au-Gel) based on chitosan (CS) and β-glycerophosphate (β-GP), which encapsulated olaparib-liposomes (OLA-lips) and CS-capped gold nanoparticles (CS-AuNPs). OLA-Au-Gel achieved the combination of mild PTT (mPTT) by CS-AuNPs and tumor DNA damage repair inhibition by OLA. The hydrogel showed good biocompatibility, injectability, and photothermal response. Under near-infrared laser irradiation, OLA-Au-Gel inhibited the proliferation of tumor cells, induced the generation of reactive oxygen species in vitro , and effectively inhibited the growth of breast tumors in vivo . OLA-Au-Gel shows a promising application prospect for inhibiting tumor development and improving the antitumor effect. Collectively, we propose a novel strategy for enhanced antitumor therapy based on the combination of mPTT and DNA damage repair inhibition.
- Published
- 2023
- Full Text
- View/download PDF
35. Expanding the Chemical Diversity of Secondary Metabolites Produced by Two Marine-Derived Enterocin- and Wailupemycin-Producing Streptomyces Strains.
- Author
-
Xia K, Shang J, Sun J, Zhu W, and Fu P
- Abstract
To expand the chemical diversity of secondary metabolites produced by two marine-derived enterocin- and wailupemycin-producing Streptomyces strains, OUCMDZ-3434 and OUCMDZ-2599, precursor feeding and solid fermentation strategies were used. Two new compounds, wailupemycins Q ( 1 ) and R ( 2 ), were isolated from the extracts of liquid and solid fermentation of OUCMDZ-3434. Furthermore, during the fermentation of OUCMDZ-3434, p -fluorobenzoic acid was added as the key biosynthetic precursor, which resulted in the isolation of eight new fluorinated enterocin and wailupemycin derivatives ( 3 - 10 ) and 10 previously reported analogues ( 11 - 20 ). From the solid fermentation extract of OUCMDZ-2599, a new sulfur-containing compound thiotetromycin B ( 21 ) and its known analogue thiotetromycin ( 22 ) were identified. Moreover, the solid fermentation strategy effectively activated the biosynthesis of siderophores ( 23 - 25 ) of strain OUCMDZ-2599. Compound 3 showed moderate antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus subsp. aureus with MIC values of 4 μg/mL. Compounds 23 - 25 were significantly capable of binding Fe(III)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
- Published
- 2023
- Full Text
- View/download PDF
36. Hierarchical Macroporous Agarose Materials with Polyethyleneimine-Assisted Multiple Boronate Affinity Binding Sites for the Separation of Neomycin.
- Author
-
Wei FY, Zheng HW, Tian JJ, Liu HY, Wei YX, Yang L, Wang CY, and Xue CH
- Subjects
- Sepharose, Silicon Dioxide chemistry, Binding Sites, Chromatography, Affinity methods, Polyethyleneimine chemistry, Boronic Acids chemistry
- Abstract
Quantification of neomycin residues in food samples demands an efficient purification platform. Herein, hierarchical macroporous agarose monoliths with multiple boronate affinity sites were established for selective separation of neomycin. The silica core was synthesized by "one-step" Stöber procedures followed by modification with amino group and incorporation of polyethyleneimine. A versatile macroporous agarose monolith was prepared by emulsification strategies and functionalized with epoxy groups. After introducing polyethyleneimine-integrated silica nanoparticles onto the agarose monolith, fluorophenylboronic acids were immobilized. The physical and chemical characteristics of the composite monolith were analyzed systematically. After optimization, neomycin showed high binding ability of 23.69 mg/g, and the binding capacity can be manipulated by changing the pH and adding monosaccharides. The composite monolith was subsequently utilized to purify neomycin from the spiked model aquatic products followed by high-performance liquid chromatography analysis, which revealed a remarkable neomycin purification effect, indicating the great potential in the separation of neomycin from complicated aquatic products.
- Published
- 2023
- Full Text
- View/download PDF
37. Mechanistic Understanding toward the Maternal Transfer of Nanoplastics in Daphnia magna .
- Author
-
Xue R, Lan R, Su W, Wang Z, Li X, Zhao J, Ma C, and Xing B
- Subjects
- Animals, Female, Daphnia metabolism, Microplastics metabolism, Polystyrenes, Water Pollutants, Chemical, Nanoparticles
- Abstract
Nanoplastics induce transgenerational toxicity to aquatic organisms, but the specific pathways for the maternal transfer of nanoplastics remain unclear. Herein, laser scanning confocal microscopy (LSCM) observations identified the specific pathways on the maternal transfer of polystyrene (PS) nanoplastics (25 nm) in Daphnia magna . In vivo and in vitro experiments showed that PS nanoplastics could enter the brood chamber through its opening and then be internalized to eggs and embryos using LSCM imaging (pathway I). In addition, PS nanoplastics were observed in the oocytes of the ovary, demonstrating gut-ovary-oocyte transfer (pathway II). Furthermore, label-free hyperspectral imaging was used to detect the distribution of nanoplastics in the embryos and ovary of Daphnia , again confirming the maternal transfer of nanoplastics through the two pathways mentioned above. The contribution from pathway I (88%) was much higher than pathway II (12%) based on nanoflow cytometry quantification. In addition, maternal transfer in Daphnia depended on the particle size of PS nanoplastics, as demonstrated by using LSCM and hyperspectral imaging. Unlike 25 nm nanoplastics, 50 nm PS nanoplastics could enter the brood chamber and the eggs/embryos (pathway I), but were not detected in the ovary (pathway II); 100 nm PS nanoplastics were difficult to be internalized by eggs/embryos and could not enter the ovary either. These findings provide insight into the maternal transfer mechanisms of nanoplastics in Daphnia , and are critical for better understanding the transgenerational toxicity of aquatic organisms.
- Published
- 2023
- Full Text
- View/download PDF
38. Cocrystallization-Driven Double-Optimized Stratagem toward Directional Self-Assembly for the First Ternary Salt Cocrystal of Cardiotonic Drug Milrinone with Different Phenolic Acids Exhibits Optimal In Vitro / Vivo Biopharmaceutical Peculiarities.
- Author
-
Meng SS, Yu YM, Bu FZ, Yan CW, Wu ZY, and Li YT
- Subjects
- Milrinone, Crystallization methods, Solubility, Sodium Chloride, Water chemistry, Cardiotonic Agents, Biological Products
- Abstract
The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize in vitro / vivo peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative in vitro properties further modulate the in vivo pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL's biopharmaceutical characteristics on both in vitro and in vivo aspects. Along this line, the first MIL ternary salt cocrystal, viz., [HMIL
+ -GA- ]-MIL-GLC-H2 O (denoted as MTSC hereinafter), has been satisfactorily constructed and precisely structurally identified by diversified techniques. The single-crystal X-ray diffraction experiment validates that a molecular salt [HMIL+ -GA- ] species cocrystallizes with one neutral MIL, two GLC, and five solvent water molecules, among which the organic constituents compose laminated hydrogen bond networks, and then are self-assembled by water molecules to a 3D supramolecular structure. The unique structural feature and stacking pattern of MTSC make both the permeability and solubility be respectively enhanced by 9.69 times and 5.17- to 6.03-fold compared with the parent drug per se . The experimental outcomes are powerfully supported by associated calculations based on density functional theory. Intriguingly, these optimal in vitro physicochemical natures of MTSC have been potently converted into strengths of in vivo pharmacokinetics, showcasing the elevated drug plasma concentration, elongated half-life, alongside advanced bioavailability. Consequently, this presentation not just contributes a brand-new crystalline form with utility values, but ushers in a new dimension of ternary salt cocrystals for improving in vitro / vivo limitations of poor drug bioavailability.- Published
- 2023
- Full Text
- View/download PDF
39. Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe.
- Author
-
Niu Y, Chen Z, Jiang Z, Yang Y, Liu G, Cheng X, Jiang Z, Zhang G, Tong L, and Tang B
- Subjects
- Sulfenic Acids metabolism, Biotin metabolism, Escherichia coli metabolism, Oxidation-Reduction, Cysteine chemistry, Escherichia coli Proteins metabolism
- Abstract
S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.
- Published
- 2023
- Full Text
- View/download PDF
40. Triethylamine-Promoted Henry Reaction/Elimination of HNO 2 /Cyclization Sequence of Functionalized Nitroalkanes and 2-Oxoaldehydes: Diversity-Oriented Synthesis of Oxacycles.
- Author
-
Lu YX, Lv XJ, Liu C, and Liu YK
- Subjects
- Cyclization, Acetals, Benzopyrans
- Abstract
The triethylamine-promoted cascade Henry reaction/elimination of HNO
2 /cyclization reaction of 2-oxoaldehydes with nitroalkanes bearing various remote functionalities is described. Both chiral and achiral nitroalkanes were applicable to this protocol, leading to a variety of oxacycles, such as chromenes, chromanes, cyclic hemiacetals, and polycyclic acetals. An unexpected regioselective photooxygenation occurred without sensitizer during derivatization to convert a derived diene product into a dioxetane by reaction with singlet oxygen, which provided chromen-2-one and benzaldehyde after fragmentation.- Published
- 2023
- Full Text
- View/download PDF
41. Synthesis of 4-Aryl-1,3,4-benzotriazepinones from Isatoic Anhydrides and Hydrazonyl Chlorides.
- Author
-
Zhang X, Pan Y, Liu T, and Wang Y
- Abstract
An efficient synthesis of 4-aryl-1,3,4-benzotriazepinones from readily available isatoic anhydrides and hydrazonyl chlorides was developed. In this facile protocol, a series of functionalized 1,3,4-benzotriazepinones were conveniently obtained with broad substrate scope and excellent functional group tolerance.
- Published
- 2023
- Full Text
- View/download PDF
42. Photodynamic Alginate Zn-MOF Thermosensitive Hydrogel for Accelerated Healing of Infected Wounds.
- Author
-
Zhang W, Wang B, Xiang G, Jiang T, and Zhao X
- Subjects
- Hydrogels pharmacology, Alginates pharmacology, Anti-Bacterial Agents pharmacology, Wound Healing, Metal-Organic Frameworks pharmacology, Photochemotherapy
- Abstract
Antibiotic resistance reduces the effectiveness of infected wound healing, and it is necessary to develop a new strategy to promote infected wound healing without using antibiotics. Here, we develop a Chlorin e6 (Ce6)-loaded zinc-metal-organic framework (MOF) thermosensitive hydrogel (Ce6@MOF-Gel) based on alginate and poly(propylene glycol) 407, which enhances antibacterial effects and promotes infected wound healing by a novel strategy of combining zinc-MOF with photodynamic therapy (PDT). Zinc-MOF can realize acid-responsive release of Ce6 and improve antibacterial performance without drug resistance by destroying the integrity of bacterial cell membranes and enhancing the production of bacterial reactive oxygen species (ROS). Additionally, Ce6@MOF-Gel enhances the stability, solubility, and photodynamic properties of Ce6. More importantly, Ce6@MOF-Gel reduces inflammation and promotes collagen deposition and re-epithelialization to facilitate infected wound healing. Collectively, the photodynamic MOF-based hydrogel provides a new, efficient, and safe way for accelerated healing of infected wounds.
- Published
- 2023
- Full Text
- View/download PDF
43. Stereospecific [3+2] Cycloaddition of Chiral Arylallenes with C,N-Cyclic Azomethine Imines.
- Author
-
Wang, Liu X, Ajitha MJ, Liu Z, Hu Y, and Huang KW
- Abstract
A novel α,β-regioselective [3+2] cycloaddition reaction of arylallene with C,N-cyclic azomethine imine is reported. The axial-to-central chirality transfer phenomenon has been disclosed with chiral allenes in the reaction. The wide substrate scope, including different functional groups and natural products, reveals the generality of the methodology. Both experiments and density functional theory calculations have been used to elucidate a plausible mechanism.
- Published
- 2023
- Full Text
- View/download PDF
44. Phosphatidylinositol 4,5-Bisphosphate Sensing Lipid Raft via Inter-Leaflet Coupling Regulated by Acyl Chain Length of Sphingomyelin.
- Author
-
Li S, Huang F, Xia T, Shi Y, and Yue T
- Subjects
- Humans, Cell Membrane chemistry, Molecular Dynamics Simulation, Membrane Microdomains chemistry, Phosphatidylinositol 4,5-Diphosphate analysis, Phosphatidylinositol 4,5-Diphosphate chemistry, Phosphatidylinositol 4,5-Diphosphate metabolism, Sphingomyelins, Phosphatidylinositols analysis, Phosphatidylinositols metabolism
- Abstract
Phosphatidylinositol 4,5-bisphosphate (PIP
2 ) is an important molecule located at the inner leaflet of cell membrane, where it serves as anchoring sites for a cohort of membrane-associated molecules and as a broad-reaching signaling intermediate. The lipid raft is thought as the major platform recruiting proteins for signal transduction and also known to mediate PIP2 accumulation across the membrane. While the significance of this cross-membrane coupling is increasingly appreciated, it remains unclear whether and how PIP2 senses the dynamic change of the ordered lipid domains over the packed hydrophobic core of the bilayer. Herein, by means of molecular dynamic simulation, we reveal that inner PIP2 molecules can sense the outer lipid domain via inter-leaflet coupling, and the coupling manner is dictated by the acyl chain length of sphingomyelin (SM) partitioned to the lipid domain. Shorter SM promotes membrane domain registration, whereby PIP2 accumulates beneath the domain across the membrane. In contrast, the anti-registration is thermodynamically preferred if the lipid domain has longer SM due to the hydrophobic mismatch between the corresponding acyl chains in SM and PIP2 . In this case, PIP2 is expelled by the domain with a higher diffusivity. These results provide molecular insights into the regulatory mechanism of correlation between the outer lipid domain and inner PIP2 , both of which are critical components for cell signal transduction.- Published
- 2023
- Full Text
- View/download PDF
45. In Situ Continuous Measurement of Salinity in Estuarine and Coastal Sediments by All-Solid Potentiometric Sensors.
- Author
-
Li Y, Liao Z, Lin X, Ding J, and Qin W
- Subjects
- Environmental Monitoring, Metals, Water, Salinity, Geologic Sediments
- Abstract
Salinity is crucial for understanding the environmental and ecological processes in estuarine and coastal sediments. In situ measurements in sediments are scarce due to the low water content and particulate adsorption. Here, a new potentiometric sensor principle is proposed for the real-time in situ measurement of salinity in sediments. The sensor system is based on paper sampling and two all-solid electrodes, a cation-selective electrode (copper hexacyanoferrate, CuHCF) and an anion-selective electrode (Ag/AgCl). The spontaneous aqueous electrolyte extraction and redox reaction can produce a Nernstian response on both electrodes that is directly related to salinity. This potentiometric sensor allows for salinity acquisition in a wide salinity range (1-50 ppt), with high resolution (<1 ppt), and at a low water content (<30%), and it has been applied for the in situ measurement of salinity and the interpretation of cycling processes of metals in estuarine and coastal sediments. Moreover, the sensor coupled to a wireless monitoring system exhibited remote-sensing capability and successfully captured the salinity dynamic processes of the overlying water and pore water during the tidal period. This sensor with its low cost, versatility, and applicability represents a valuable tool to advance the comprehension of salinity and the salinity-driven dissolved-matter variations in estuarine and coastal sediments.
- Published
- 2023
- Full Text
- View/download PDF
46. Anti-fouling TiO 2 -Coated Polymeric Membrane Ion-Selective Electrodes with Photocatalytic Self-Cleaning Properties.
- Author
-
Liu T, Liang R, and Qin W
- Abstract
Nowadays, using a polymeric membrane ion-selective electrode (ISE) to achieve reliable ion sensing in complex samples remains challenging because of electrode fouling. To address this challenge, we describe a polymeric membrane ISE with excellent anti-fouling and self-cleaning properties based on surface covalent modification of an anatase TiO
2 coating. Under ultraviolet illumination, the reactive oxygen species produced by photocatalytic TiO2 can not only kill microorganisms but also degrade organic foulants into carbon dioxide and water, and a formed superhydrophilic film can effectively prevent the adsorption of foulants, thus inhibiting the occurrence of biofouling and organic fouling of the sensors. More importantly, residual foulants could be fully self-cleaned through the flow of water droplets. By using Ca2+ -ISE as a model, an anti-fouling polymeric membrane potentiometric sensor has been developed. Compared to the unmodified electrode, the TiO2 -coated Ca2+ -ISE exhibits remarkably improved anti-biofouling properties with a low bacterial adhesion rate of 4.74% and a high inhibition rate of 96.62%. In addition, the proposed electrode displays unique properties of anti-organic dye fouling and a superior self-cleaning ability even after soaking in a concentrated bacterial suspension of 109 CFU mL-1 for 60 days. The present approach can be extended to improve the fouling resistance of other electrochemical or optical membrane sensors and is promising for the construction of contamination-free sensors.- Published
- 2023
- Full Text
- View/download PDF
47. Identification of a Key Loop for Tuning Transglycosylation Activity in the Substrate-Binding Region of a Chitosanase.
- Author
-
Sun H, Zhao L, Mao X, Cao R, and Liu Q
- Subjects
- Chitin chemistry, Glycoside Hydrolases chemistry, Catalysis, Chitosan chemistry
- Abstract
Csn-PD, a glycoside family 46 chitosanase from Paenibacillus dendritiformis , exhibits endotype hydrolysis of chitosan and produces (GlcN)
2 as the major product. Here, we report the crystal structure of Csn-PD at 1.68 Å resolution. The structure contains 14 α-helices and two β-strands that fold into two globular domains with the substrate bound between them. To evaluate the function of a loop in the substrate-binding region (residues 112-116, NDKHP), a mutant Csn-PDL1, in which this loop was deleted, was generated. Hydrolysis of chitosan by the mutant yielded chitooligosaccharides (COSs) with higher degrees of polymerization (DP) than the wild-type enzyme. Excitingly, (GlcN)6 was produced from smaller COSs via transglycosylation activity of the mutant. Hence, the catalytic performance of a chitosanase was altered by modification of a loop in the substrate-binding regions. Our novel data on a chitosanase with transglycosylation activity offer a promising way to produce COSs with high DP.- Published
- 2023
- Full Text
- View/download PDF
48. Peptide Stapling through Site-Directed Conjugation of Triazine Moieties to the Tyrosine Residues of a Peptide.
- Author
-
Zhang Y, Yin R, Jiang H, Wang C, Wang X, Wang D, Zhang K, Yu R, Li X, and Jiang T
- Subjects
- Amino Acid Sequence, Tyrosine, Peptides chemistry
- Abstract
Peptide stapling is a strategy for improving the biological properties of peptides. Herein, we report a novel method for stapling peptides that utilizes bifunctional triazine moieties for two-component conjugation to the phenolic hydroxyl groups of tyrosine, which enables efficient stapling of unprotected peptides. In addition, we applied this strategy to the RGD peptide that can target integrins and demonstrated that the stapled RGD peptide had significantly improved plasma stability and integrin-targeting ability.
- Published
- 2023
- Full Text
- View/download PDF
49. Application of Quorum Sensing in Metabolic Engineering.
- Author
-
Cao Z, Liu Z, and Mao X
- Subjects
- Bacteria genetics, Quorum Sensing physiology, Metabolic Engineering
- Abstract
Metabolic engineering is widely utilized in the food and other fields and has the benefits of low-cost substrates, eco-friendly fermentation processes, and efficient substrate synthesis. Microbial synthesis by metabolic engineering requires maintaining the productive capacity of the microorganism. Moreover, economic reasons limit the use of inducers in the exogenous synthesis pathway. Most unicellular microorganisms can interact by emitting signaling molecules; this mechanism, known as quorum sensing (QS), is an autoinduced system of microorganisms. With the deepening research on QS systems of different microorganisms, its components are widely used to regulate the metabolic synthesis of microorganisms as a dynamic regulatory system. In this Review, we described the typical bacterial QS mechanisms. Then, we summarized various regulatory strategies for QS and their applications to metabolic engineering. Finally, we underlined the potential for QS modularity in future metabolic engineering and suggested stimulating research on fungal QS systems.
- Published
- 2023
- Full Text
- View/download PDF
50. Design, Synthesis, and Anti-Cancer Evaluation of Novel Cyclic Phosphate Prodrug of Gemcitabine.
- Author
-
Zhang L, Qi K, Xu J, Xing Y, Wang X, Tong L, He Z, Xu W, Li X, and Jiang Y
- Subjects
- Male, Humans, Gemcitabine, Phosphates therapeutic use, Organophosphates, Esters therapeutic use, Cell Line, Tumor, Prodrugs, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology
- Abstract
ProTide and cyclic phosphate ester are two successful prodrug technologies to overcome the limitations of nucleoside drugs, among which the cyclic phosphate ester strategy has not been widely used in the optimization of gemcitabine. Herein, we designed a series of novel ProTide and cyclic phosphate ester prodrugs of gemcitabine. Cyclic phosphate ester derivative 18c exhibits much higher anti-proliferative activity than positive control NUC-1031 with IC
50 s of 3.6-19.2 nM on multiple cancer cells. The metabolic pathway of 18c demonstrates that 18c 's bioactive metabolites prolong its anti-tumor activity. More importantly, we separated the two P chiral diastereomers of gemcitabine cyclic phosphate ester prodrugs for the first time, revealing their similar cytotoxic potency and metabolic profile. 18c displays significant in vivo anti-tumor activity in both 22Rv1 and BxPC-3 xenograft tumor models. These results suggest that compound 18c is a promising anti-tumor candidate for treating human castration-resistant prostate and pancreatic cancer.- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.