查找使用阿拉丁产品的科研文献

DOTA-grafted Cationic Polymers Behaving as Powerful Macromolecular Resistance-reversal Agents (MRRAs) Combating Against New Delhi Metallo-β-lactamase (NDM)-producing Bacteria

Ruixue Wang,Jian Zhang,Yun li,Liping Qiao,Zhuorui Dong,Dandan Cui,Peirong Bai,Liping Li,Bing Cao,Ruiping Zhang

New Delhi metallo-β-lactamase (NDM)-producing bacteria have posed a significant threat to human health. To navigate this tricky problem, numerous NDM inhibitors have been explored, showing great antibacterial synergy. But there are still be some problems to be tackled, such as suboptimal efficacy, rapid resistance evolution, and high cytotoxicity. Herein, we engineer two macromolecular resistance-reversal agents (MRRAs) via pharmacophore integration: linear (MRRAL) and nanostructured (MRRAN) topologies, both coordinating metal ion chelator-DOTA motif into tunable polycationic scaffolds. And we validate their efficacy through 4 clinically isolated NDM-producing pathogens. MRRAs present excellent effect boosting meropenem (MEM) to fight against those superbugs with the fractional inhibitory concentration indices much less than 0.5. Notably, the nanostructured MRRAN exhibited superior potency compared to its linear counterpart MRRAL under the same concentration of the active group of “DOTA.” Mechanistic studies revealed that MRRAN could achieve bacterial membrane targeting through charge-mediated accumulation, exerting triple-action synergistic mechanisms: 1) physical membrane disruption through powerful local cationic surface interactions and hydrophobic force, 2) precise Zn 2 + depletion from membrane-associated NDM, and 3) localized DOTA enrichment for enhanced metalloenzyme inhibition. Our findings established a paradigm for rational design of macromolecule metalloenzyme inhibitors through spatial organization of pharmacophores, offering a promising therapeutic strategy against NDM-mediated carbapenem resistance.

Β-Lactoglobulin interacting with phlorizin alters its GI digestive peptide profile and synergistically enhances intestinal accessibility and MUC2 secretion on LS174T cells

Haiyan Xue,Yalin Tan,Baoyuan He,Yan Zhou,Bowei Ding,Yawen Wu,Jun Ma,JiaYi Wang,Wenmin Dong

Phlorizin (PZ), a naturally occurring flavonoid glycoside in Malus exhibits dual therapeutic potential as an antioxidant and antidiabetic agent, however its clinical translation is constrained by poor aqueous solubility (<0.1 mg/mL) and suboptimal bioavailability. To address these limitations, this study examined supramolecular complexation with β-lactoglobulin (β-LG), a whey protein carrier capable of hydrophobic nutrient transport and known for its immunomodulatory properties. Furthermore, the molecular binding mechanism, gastrointestinal stability, and synergistic effects of the PZ–β-LG complex on intestinal mucosal secretion were systematically characterized by integrating computational simulations, spectroscopic validation, and in vitro functional assays. Molecular dynamics simulations revealed that the PZ preferential bound within the calyx domain of β-LG (ΔG = −8.3 kcal/mol) through hydrophobic interactions and hydrogen bonding, as evidenced by emerging UV–Visible absorption peaks between 300 and 350 nm and intrinsic fluorescence spectroscopy. Simulated gastrointestinal digestion coupled with Liquid Chromatography–Tandem Mass Spectrometry(LC-MS/MS) peptidomics demonstrated a significant reduction in β-LG antigenicity reduction(52.1% vs. free β-LG; P  < 0.01), which might be attributed to the enhanced gastrointestinal hydrolysis efficiency and the masking of immunoreactive epitopes Notably, 2 digestion-resistant peptides (VAGTWY-42 and LDAQSAPLR-89) persisted across all groups, suggesting potential allergenicity hotspots that may require further investigation. Cellular assessments using intestinal epithelium LS174T cells revealed that β-LG complexation reduced PZ associated cytotoxicity by 62% ( P  < 0.05) while synergistically upregulating the expression of mucin-2 (MUC2) at both transcriptional (2.5-fold increase) and secretory levels (2.1-fold elevation vs. control). Overall, these findings indicate that hydrophobic-driven complexation PZ with β-LG not only enhances the bioavailability of polyphenol but also decreases the antigenicity of protein carrier in intestine cells.

β-hydroxybutyrate regulates microglia M1/M2 polarization and phagocytosis through the JAK1/STAT1 pathway to reduce neuroinflammation and exert anti-epileptic effects

Yang Hui,Wang Huifen

Hydroquinone Hydroxypropyl-β-cyclodextrin Inclusion Complex Based Topical Cream as an Effective Treatment of Melasma by Releasing Hydroquinone in a Controlled Manner

Mu Yinling,Liu Hongbing,Guo Xianglin,Liu Yiyu,Pan Wanbing,Zhao Fan,He Haibing,Gou Jingxin,Tang Xing,Yin Tian,Zhang Yu

Objective Hydroquinone (HQ) is globally regarded as the gold-standard topical agent for melasma treatment. However, its clinical utility is limited by several challenges: susceptibility to oxidation induced by light, air, and metal ions, which generates harmful byproducts and triggers adverse effects (e.g., skin irritation, pruritus, and dermatitis). Moreover, excessively high concentration in the skin of hydroquinone due to the burst release of HQ may cause melanocyte cytotoxicity, while systemic penetration raises additional safety concerns. To overcome these limitations and enhance the therapeutic applicability of HQ, this study aims to develop strategies that mitigate its instability and optimize its delivery profile. Methods In this study, an oil-in-water cream containing hydroquinone cyclodextrin inclusion complex (HQ-HPCD) was designed with PO as the oil phase matrix to improve the treatment of melasma. Results As expected, the in vitro release profile of HQ-HPCD cream exhibited near-zero-order kinetics, effectively mitigating the irritation associated with burst release-induced peak concentrations. The HQ-HPCD inclusion complex demonstrated enhanced photostability and oxidative resistance compared to free HQ. Then it was confirmed by B16F10 cells that the HQ-HPCD increased the IC 50 of HQ by 4.6 times. Moreover, skin condition, tyrosinase activity, SOD (Superoxide Dismutase), MDA (Malondialdehyde) and melanin content in the mice were detected and the results were in line with the in vitro assays, which showed that PO-HQ-HPCD cream has higher resistance to melanin deposition and lower irritation. Conclusions This study successfully developed a topical formulation that enhances the stability of hydroquinone (HQ) while achieving its sustained release in the epidermal layer, thereby improving its clinical applicability of melasma.

Intelligent pH Sensing Films based on Chitosan/Cellulose Nanocrystals with Blood Peach Anthocyanins and β-Cyclodextrin-Encapsulated Carvacrol for Monitoring Shrimp Freshness

Zhou Qi,Wang Yangguang,Yuan Gaofeng,Dai Qiuping

Intelligent indicator films were successfully fabricated by incorporating blood peach anthocyanins (BPA) and β-cyclodextrin-encapsulated carvacrol (β-CD@CAR) into chitosan/cellulose nanocrystals (CN) matrices. The prepared films were comprehensively characterized using multiple analytical techniques. The addition of BPA and β-CD@CAR significantly enhanced the films' UV–vis radiation blocking ability, thermal stability, as well as antioxidant (DPPH radical scavenging rate: 45.89% for CN-EO-1A film, vs. 7.71% for pure CN film) and antibacterial activities ​(inhibition zones of 10.24 mm and 8.52 mm against Escherichia coli and Staphylococcus aureus , respectively). Specifically, β-CD@CAR notably improved the mechanical properties of the films and strengthened their color stability and pH responsiveness. Notably, the CN film with 0.5% (w/w) BPA and β-CD@CAR (CN-EO-0.5A) demonstrated excellent performance, with a tensile strength of 10.99 MPa and an elongation at break of 91.66%. Additionally, it exhibited remarkable color responsiveness to different pH values and ammonia exposure.​ The effectiveness of the CN-EO-0.5A in monitoring shrimp freshness during storage at 4 °C was further evaluated. The film could visually indicate the freshness levels of shrimp, distinguishing among fresh, sub-fresh, and spoiled states through distinct color changes. Strong correlations were established between the total color difference of the CN-EO-0.5A and key freshness indicators of shrimp, including total volatile basic nitrogen ( R 2  = 0.9630) and total viable count ( R 2  = 0.9983). Therefore, the CN-EO-0.5A film showed promise for real-time monitoring seafood freshness.

Berberine Alleviates Pancreatic β-Cell Ferroptosis and Injury in db/db Mice by Regulating the AGE/RAGE Pathway: Insight from Proteomic Analysis

Liu Xiao-cui,Liu Ya-ge,Lv Yong-ning,Deng Bin

Objective This study aimed to investigate the protective effects of berberine (BBR) on pancreatic β-cells and explore its underlying molecular mechanisms via a proteomics-based approach. Methods Using db/db mice as a diabetes model, BBR was administered at doses of 100 mg/kg and 200 mg/kg for 8 weeks. The protective effects were assessed through fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), pancreatic histopathological analysis, and TUNEL staining. Proteomic analysis employing the data-independent acquisition (DIA) method identified differentially expressed proteins (DEPs), whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to identify potential pathways. Molecular docking, surface plasmon resonance (SPR), and immunohistochemistry (IHC) were performed to validate key target proteins. Results BBR significantly reduced blood glucose levels, improved insulin resistance, enhanced insulin secretion, and reversed pathological changes in pancreatic tissue, thereby alleviating β-cell damage. Proteomic analysis identified 171 DEPs, implicating the AGE/RAGE signaling pathway as a key mechanism through which BBR exerts its protective effects. The results of molecular docking, SPR and IHC confirmed that BBR markedly inhibited the activation of the AGE/RAGE pathway. Conclusions These findings suggest that BBR alleviates pancreatic β-cell damage, potentially through regulation of the AGE/RAGE pathway, providing insights into its therapeutic potential for diabetes management.

Time-resolved fluorescence microspheres-antibody-penicillin-binding protein assisted construction of immunochromatographic assay for sensitive detection of 22 β-lactams in milk

Sun Yawei,Deng Xiangjie,Luo Changwei,Ma Wentao,Liu Wanjing,Wang Jinkui,Li Qingyue,Bu Tong,Zhang Xiya

A sensitive immunochromatographic assay (ICA) using time-resolved fluorescence microspheres (TRFMs) coupled with an indirect-labeling mode was developed for simultaneously determining 22 kinds of β-lactams in milk samples. The TRFMs labeled anti-receptor monoclonal antibodies (mAbs) conjugated to penicillin-binding proteins (PBPs) as ternary TRFMs-mAb-PBPs (TMP) nanoscaffolds provide excellent solubility, brightness, and stability. Thanks to the fact that they not only fully expose the binding sites of PBPs, thereby enhancing the biological affinity of PBPs towards the target, but also generated superb fluorescence signals, the versatile TMP manifested unique possibilities as efficient probes for ICA with remarkable enhancement in sensitivity in β-lactams screening. The results showed that the standard curves of the 22 varying β-lactams displayed linearity in their respective concentration ranges ( R 2 > 0.98), with the cutoff values of 1–100 ng/mL. The constructed TMP-ICA was successfully applied to the analysis of real milk, with consistent results compared with liquid chromatography-tandem mass spectrometry (LC-MS), providing an effective method for sensing β-lactams in food matrices. Graphical

Covalent Surface Functionalization of Semiconducting Polymer Dots with β-Cyclodextrin for Fluorescent Ratiometric Assay of Cholesterol through Host–Guest Inclusion and FRET

Junyong Sun,Sufan Wang,Feng Gao

Special functionalization of semiconducting polymer dots (Pdots) is highly desired to expand their applications in chemo/biosening. Herein, carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1′,3}-thiadiazole)] dots covalently tagged with aminated β-cyclodextrin (NH2–CD) have been designed to construct a ratiometric sensor for cholesterol (Cho). Using CD-Pdots as energy donors with rhodamine B (RB) as energy acceptors, a fluorescence resonance energy transfer (FRET) pair has been built because the host–guest interaction between RB and CD attached to Pdots brings donors and acceptors into close proximity. In the presence of Cho, the acceptors will depart from the donors because of the competitive inclusion interaction between Cho and RB with CD, resulting in the hindering of the FRET process between CD-Pdots and RB. On the basis of the turn-on fluorescence of CD-Pdots and turn-off fluorescence of RB, a sensitive ratiometric method for the determination of Cho in the concentration range from 25 to 350 nM with a detection limit of 4.9 nM was achieved. The proposed method was validated to determine free Cho in human serum samples with satisfactory results.

Engineering of a kaolin/SLS-functionalized biochar@β-cyclodextrin composite for adsorption of o-nitrophenol; optimization, mechanistic study, and Box–Behnken design

Abdelazeem S. Eltaweil,Nouf Al Harby,Mervette El Batouti,Eman M. Abd El-Monaem

In this investigation, a good adsorbent was created by combining kaolin, β-cyclodextrin, and sodium lauryl sulfate-functionalized biochar, resulting in a new Kaol/SLS-BC/β-CD composite. Assorted analyses were used to characterize the chemical/physical properties of the Kaol/SLS-BC/β-CD. The adsorption capability of the Kaol/SLS-BC/β-CD was evaluated, using an experimental adsorption batch study of o-nitrophenol (o-NP). The experimental batch experiments showed that o-NP removal of 100% was achieved at room temperature after 180 minutes with pH = 3, Kaol/SLS-BC/β-CD dose = 10 mg, and o-NP concentration = 50 mg L−1. Kinetic and isotherm analyses of the experimental data implied that the Freundlich isotherm model and the pseudo-second-order kinetic model were obeyed for the o-NP adsorption reaction. Surprisingly, the maximal adsorption capacity of Kaol/SLS-BC/β-CD towards o-NP, calculated from Langmuir analysis, was 588.24 mg g−1. The optimization of o-NP adsorption onto Kaol/SLS-BC/β-CD was investigated using response surface methodology (RSM) based on a Box–Behnken design (BBD) with three independent variables: initial o-NP concentration, adsorbent dosage, and contact time. The quadratic response surface model was validated through analysis of variance (ANOVA). The reduced quadratic model demonstrated good agreement between the predicted and experimental results. Thus, the validated model can be reliably applied to predict the optimal conditions for o-NP adsorption onto Kaol/SLS-BC/β-CD. The mechanistic study of the o-NP adsorption onto Kaol/SLS-BC/β-CD clarified that the process may occur via Lewis acid–base, pore-filling, coordination bond, hydrogen bond, and pi–pi interactions. Notably, the cycling test indicated that the Kaol/SLS-BC/β-CD could be reused for six adsorption cycles of o-NP with promising efficacy.

The effect of combining the enzymolysis of snail digestive enzyme and β-glucanase on the release of flavor in Lentinus edodes powder

Xiaoyu Ye,Jiaqi Li,Xia Ma,Xueqi Zhao,Liang Yao,Yuling Qu,Wenwei Zhang,Fengyun Zhao,Jianmin Yun

In this paper, the regulatory effect of combining the enzymolysis of snailase and β-glucanase on the flavor release of Lentinula edodes powder was analyzed. The flavor attributes and differences of volatiles before and after enzymatic hydrolysis were evaluated using gas chromatograph-ion mobility spectrometry, electronic nose, and quantitative descriptive analysis. The results showed that a total of 70 volatile compounds were identified, the flavor contributions of nitrogen oxides, sulfides, and aromatic compounds in L. edodes were significantly enhanced after enzymatic hydrolysis. The enzymatically treated L. edodes received the highest scores in fruity flavor and sour flavor. After enzymatic hydrolysis of shiitake, 2-methyl butanal (bitter almond note) and 1-octen-3-one (grassy note) showed a significant decrease in flavor contribution, while the flavor contribution of β-caryophyllene and acetic acid, associated with sweet and sour flavor, significantly increases. Principal component analysis revealed that the flavor profile of shiitake powder was significantly reconstructed after enzymatic treatment

Trinity synergy of guanidine-functionalized polymer brush-modified β-cyclodextrin polymer magnetic beads for recognition of phosphopeptides in serum of Alzheimer's disease

Mei Yang,Yuanzhi Zhao,Shoulin Chen,Chunbo Liu,Yinghua Yan,Haihua Tian

Systematic profiling of protein phosphorylation is pivotal for elucidating the molecular pathogenesis of Alzheimer's disease (AD). Here, we report the rational design of ‌magCEP@PEI@G‌, a multifunctional magnetic adsorbent integrating β-cyclodextrin–epichlorohydrin polymers, polyethyleneimine (PEI), and guanidino functional groups to enable synergistic phosphopeptide enrichment. This hybrid material achieves unprecedented performance: ‌10-cycle reusability‌ with >95% retention of enrichment efficiency, an ultra-low limit of detection (‌0.2 fmol‌), exceptional selectivity (‌5000:1‌ phospho/non-phospho peptide ratio), rapid elution (‌10 min‌), and near-perfect recovery (‌105.0 ± 0.5%‌). Applied to serum samples from three AD patients, magCEP@PEI@G enabled the robust identification of ‌135 unique phosphopeptides. These results establish magCEP@PEI@G as a highly efficient, scalable platform for the sensitive enrichment of low-abundance phosphopeptides and hold substantial promise for the ‌early diagnosis of Alzheimer's disease‌.

A Study on the Formation and Mechanisms of Worm-Like β-Lactoglobulin Self-Assemblies and Their Role in Regulating Fibrillar Self-Assemblies

Mingyu Qi,Zihan Yin,Risheng Jin

This study investigated the formation, structural characterization, cross-nucleation behavior, and functional properties of worm-like β-lactoglobulin (β-Lg) self-assemblies induced by heat treatment at 85°C under neutral pH conditions. The assembly process was monitored using SDS–PAGE, free thiol content determination, transmission electron microscopy (TEM), thioflavin T (ThT) fluorescence, ζ-potential, surface hydrophobicity, Fourier transform infrared spectroscopy (FTIR), and molecular dynamics (MD) simulations. The results indicate that heating promotes disulfide bond rearrangement and conformational changes, leading to the formation of a stable worm-like self-assembled structure. This is specifically reflected in the ζ-potential shifting from −16.8 ± 0.2 to −36.5 ± 0.3, an increase in surface hydrophobicity (from 810 ± 8.5 to 2643 ± 10.2), and a decrease followed by an increase in β-sheet content (from 36.12% to 28.35% to 29.25%), revealing structural changes during the formation of the worm-like self-assembled structures. Molecular dynamics simulations revealed that heating increased structural openness and enhanced residue mobility (Leu87, Ala111, Val128 RMSF > 2 Å). Cross-seeding experiments indicate that worm-like fibers influence the fiberization kinetics by prolonging the hysteresis phase and modulating the fluorescence intensity (depending on the seeding concentration); the fluorescence intensity during the plateau phase increased by 26.30%. Functionally, the appropriate incorporation of worm-like fiber bundles improves emulsification (emulsification capacity increased to 43.53% ± 0.3%) and foaming properties (foaming capacity increased to 142.56% ± 0.1%), whereas excessive aggregation weakens these properties. These findings provide new insights into the controlled formation of β-Lg worm-like assemblies and their potential as functional ingredients in food systems.