Despite their potential, alkali-treated konjac glucomannan (KGM) gels are limited by excessive brittleness and a lack of eco-friendly synthesis methods, creating an urgent need for more durable and 'green' alternatives. In this study, highly stable KGM gels were constructed under low-alkali conditions by adjusting the ethanol content. The results showed that intermolecular hydrogen bonding and hydrophobic interactions were enhanced with increasing ethanol concentration (0-20% v/v) under low-alkaline conditions. The physicochemical properties of KGM gels showed dynamic improvement, with denser micro-network morphology and simultaneous enhancement of thermal stability. However, the addition of a high ethanol concentration (20% v/v) tended to trigger local aggregation, disrupting the gel network structure. At an ethanol addition of 15%, the hydrogen bonding and hydrophobic interactions of KGM gels reached an optimal equilibrium, exhibiting the most compact gel network and excellent resistance to deformation. This study reveals the regulation of the microstructure and macroscopic properties of KGM gels by ethanol, which provides theoretical support for the construction of high-performance KGM gels under low-alkali conditions.
Pseudomonas aeruginosa is a predominant spoilage organism in meat products. The extensive use of antimicrobial preservatives has, however, led to the emergence of resistant strains. Mitigating the resistance of foodborne P. aeruginosa to conventional preservatives has become a critical challenge in food safety. Piperonylpiperazine (Pip), a piperazine derivative sourced from Ruta chalepensis, was first examined in this work as a novel agent capable of both suppressing virulence and enhancing preservative efficacy against P. aeruginosa, with its mode of action elucidated. At sub-inhibitory concentrations, Pip strongly suppressed the production of virulence factors and potentiated the susceptibility of P. aeruginosa to the common preservative EDTA. Mechanistically, a multi-pronged approach involving pull-down assay, transcriptomic profiling, SPR analysis, and gene knockout models demonstrated that Pip binds specifically to the LYS-164 and ASP-35 residues of the RhlI synthase, blocking the quorum sensing (QS) signaling cascade. This QS disruption led to reduced virulence factor production and attenuated pathogenicity in a Caenorhabditis elegans model. The compromised QS system subsequently induced oxidative stress, which disrupted cell membrane integrity and permeability, thereby potentiating EDTA's antibacterial action. The practical application of this synergistic combination was validated in a chicken meat model, where the Pip-EDTA mixture significantly curtailed spoilage. These findings suggest that Pip is a highly promising natural additive that can be used in combination with existing preservatives like EDTA to enhance food safety and extend the shelf life of meat products by effectively controlling resistant P. aeruginosa.
A novel quinoline-based fluorescent probe, HSS, incorporating sulfuryl hydrazide, was synthesized for the selective detection of Zr4+ in environmental and biological systems. The probe was structurally characterized by nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HR-MS). Fluorescence response to Zr4+ was investigated in a DMSO/H2O (1:1, v/v) solvent system. Binding stoichiometry and affinity were determined using Job's plot and Benesi-Hildebrand analysis, and the sensing mechanism was explored through density functional theory (DFT) calculations of frontier molecular orbital energies. HSS exhibited a selective "turn-on" green fluorescence upon Zr4+ binding, forming a 1:1 complex with a binding constant of 4.3 & times; 10(6) M-& sup1;. The probe demonstrated a detection limit of 2.68 & times; 10(-)(8) M, effective performance across a pH range of 4 similar to 10, and no interference from common metal ions. DFT studies confirmed a photoinduced electron transfer (PET)-based sensing mechanism. The rapid and sensitive fluorescence response enabled successful applications in live-cell imaging and on-site Zr4+ monitoring via smartphone-based detection, highlighting its potential for environmental and biomedical analysis.
Although aptamer-based biosensors offer significant potential for small molecules, the performance of single aptamers is often constrained by an inherent trade-off between rapid binding kinetics and high affinity. To resolve this bottleneck, we chose histamine, a crucial food safety indicator in seafood, as a model target, and rationally designed a synergistic kinetic-relay aptamer pair (SKRAP) as recognition components consisting of two histamine-targeted aptamers: a fast-capture aptamer (L2) with high association rate and a stable-lock aptamer (HIS3-T2) with superior binding affinity. Bio-layer interferometry and molecular docking validated the synergistic kinetic-relay recognition mechanism: L2 rapidly grabbed histamine due to its higher association rate, while HIS3-T2 sequentially trapped the dissociated target through more stable multi-hydrogen-bond interactions, jointly lowering equilibrium dissociation constant (Kd) and dissociation rate. Then PtFe nanozyme with robust peroxidase-like activity was synthesized as a signal amplification component and the catalytic mechanism was thoroughly studied. The SKRAP@PtFe complex was immobilized on chitosan/polyethylene glycol-modified paper to fabricate a smartphone-assisted colorimetric biosensor. Target-induced SKRAP folding created steric hindrance suppressing nanozyme catalysis, generating quantitative color signals within 10min. The biosensor achieved a wide linear range (3.05-781.25nM) and a low limit of detection (2.21nM), achieving highly selective and accurate quantification of histamine in raw and processed seafood. Beyond histamine, the proposed synergistic kinetic-relay aptamer pair design holds great promise as a modular sensing toolkit for rapid and sensitive analysis of other small molecules in complex real-world samples.
Green mold, caused by Penicillium digitatum (Pd), is a major postharvest disease affecting citrus fruits. This study investigated the biocontrol efficacy and possible mechanisms of the antagonistic yeast Meyerozyma caribbica (Mc), isolated from orchard soil, against P. digitatum in postharvest mandarin fruit. M. caribbica reduced green mold incidence, lesion diameter, P. digitatum spore germination, and germ tube length in a concentration-dependent manner. Microscopic observations showed that M. caribbica cells adhered to P. digitatum hyphae. Population dynamics analysis further revealed that M. caribbica rapidly colonized citrus wounds and persisted on fruit surfaces during storage. In a 30-day natural storage trial, M. caribbica-treated fruit exhibited a lower decay rate than the control fruit (9.91 % vs. 29.48 %) and reduced weight loss (2.32 % vs. 3.64 %), without adversely affecting firmness, TSS, or titratable acidity. NBT staining and H2O2 content determination provided direct evidence that M. caribbica reduced excessive ROS accumulation induced by P. digitatum. In the Mc + Pd treatment, the activities of ROS-scavenging enzymes, including CAT, SOD, APX, and GR, were enhanced, and the levels of non-enzymatic antioxidants, including ascorbic acid and glutathione, were higher than those in the Pd treatment. Consistently, M. caribbica reduced MDA content and cell membrane permeability by 29.89 % and 15.46 %, respectively, on day 5 compared with the Pd treatment. In addition, defense-related enzyme activities, including PPO, POD, PAL, LOX, and GLU, as well as the total phenolic and flavonoid contents, were markedly increased in the Mc + Pd treatment group. Overall, M. caribbica suppresses citrus green mold through multiple possible modes of action, including the suppression of P. digitatum development, successful colonization, regulation of ROS homeostasis, and enhancement of tissue-associated antioxidant and defense responses. These findings suggest that M. caribbica Y1 has potential as an eco-friendly biocontrol agent for postharvest citrus disease management.
Fluorescence hydrogels have become attractive candidates for monitoring food freshness; however, the ability to improve anti-interference, broaden the color variation range, and introduce multifunctionality remains limited. Here, an ingenious fluorescence hydrogel design strategy for monitoring food freshness is proposed via integrating an OH--responsive dye into functional matrices. By adjusting the intermolecular charge transfer and π-π stacking effect, nitrobenzoxadiazaole-based dye BOD-R1 was prepared and responded to biogenic amines via nucleophilic substitution. Embedding BOD-R1 in benzene-1,4-diboronic acid, poly(vinyl alcohol) (PVA), agarose (AG), and carboxymethyl cellulose (CMC) produced hydrogel R1@BAPC, which exhibited antifreezing ability, self-repairing function, high adhesion, and interface self-adaptability. Notably, the fluorescence color of R1@BAPC progressively changed from blue to yellow, as the amount of target putrescine (Put) increased, and then extracted into RGB values, in which G/B acted as the quantitative output. The hydrogel achieved a limit of detection (LOD) of 0.26 ppm for Put and completed detection within 85 s. Real sample analyses with shrimp, chicken, and pork suggested that the test results aligned well with those of the standard method, supporting excellent practical usability. The BOD-R1/BAPC design not only provides a distinct route for the synthesis of multifunctional hydrogels but also provides a portable platform for monitoring food freshness, with potential benefits for healthy food supply.
Background Our preliminary studies identified the arylpiperazine derivative NAF19 as a promising therapeutic agent against prostate cancer, though its precise mechanisms remained unclear.Methods Network pharmacology was utilized to pinpoint both therapeutic targets and disease-related targets. Functional assessments of cells were conducted using the CCK-8 method and wound-healing assays to analyze the effects of NAF19 on LNCaP cell proliferation and migration, respectively. The effect of NAF19 on the cell cycle progression of prostate cancer cells was examined using flow cytometry, while phosphorylation of AKT and PI3K was assessed using Western blotting.Results The anti-proliferative activity of NAF19 increased with higher doses and longer durations of treatment. The wound healing assay confirms its strong inhibitory effect on cell migration. Western blotting results indicate that NAF19 influences EMT-related protein expression, leading to elevated E-cadherin and decreased Vimentin and N-cadherin levels. Further mechanistic investigation showed that NAF19 significantly reduced the expression of CXCR4, as well as phosphorylated PI3K and Akt proteins. Western blot results confirmed that NAF19 downregulated Skp2 while increasing the levels of p27 and p21, suggesting involvement of the Skp2/p27/p21 signaling pathway. Molecular docking analysis demonstrated that NAF19 binds strongly to CXCR4, exhibiting a binding energy of -9.6 kcal/mol.Conclusions This investigation confirms that NAF19 acts as a new CXCR4 antagonist, effectively suppressing several cancer-promoting pathways in prostate cancer, such as PI3K/AKT signaling, cell cycle advancement, and EMT.
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Background We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, and found significant differences in pyrimidine metabolites. The PMGs is associated with the clinical prognosis of several cancers, but its biological role in PCa is still unclear.Methods This study extracted 98 reliable PMGs, and analyzed their somatic mutations, expression levels, and prognostic significance. Unsupervised clustering was applied to classify patients with PCa into clusters based on six PMGs that were related to the prognosis of PCa. The TME, gene mutations, and immune escape ability were compared among the clusters. A scoring algorithm based on prognostic PMGs, referred to as the PMGscore, was developed. TK1 was identified and the biological functions of TK1 were determined using loss-of-function experiments. RNA sequencing was subsequently performed to determine the molecules associated with the underlying mechanisms of TK1 function.Results In total, six out of 98 PMGs simultaneously exhibited differential expression in PCa and were correlated with BCR. Patients were clustered into two clusters according to the expression levels of these six PMGs, which reflected distinct clinical outcomes and immune cell infiltration characteristics. Clinical features, tumor prognosis, and functional annotation were analyzed. Subsequently, we constructed a prognostic signature using these six PMGs. In combination with other clinical traits, we found that the six PMGs’ prognostic signature was an independent prognostic factor for patients with PCa. Finally, we found that the expression of TK1 was higher in CRPC tissues than in PCa tissues in three GEO datasets. The results indicated that TK1 promotes the growth and metastasis of PCa cells.Conclusions We provide evidence for a PMG signature for PCa patients to accurately predict clinical prognosis. TK1 plays crucial roles in the progression of PCa cells and can be used as a potential therapeutic target for CRPC.
Harnessing dandy mechanical property, hydrogels facilitate the construction of wearable fluorescence sensors for minimally-invasive monitoring pesticide residue in living crops, while the interface self-adaptability and detection accuracy remain hugely challenging. Herein, blue-emission aggregation-induced emission nanoparticles (b-TPE NPs) and red-emission Mn-doped ZnS quantum dots (r-Mn@ZnS QDs) are encapsulated inside agarose, borax, and polyvinyl alcohol-co-constituted hydrogel to construct dual-color TPE@Mn@ZnS@AG@PVA as wearable crop sensor. Owing to specific recognition of r-Mn@ZnS QDs by thiophannate-methyl (TM), the customized TPE@Mn@ZnS@AG@PVA shows a gradual color evolution from reddish purple to blue with high resistance to environmental and experimental interferences via quenching r-Mn@ZnS QDs' fluorescence by target-induced aggregation and photo-induced electron transfer while acting negligible disturbance in blue fluorescence of b-TPE NPs, consequently achieving TM dual-color assay with limit of detection at 0.045 µg mL-1. Additionally, TPE@Mn@ZnS@AG@PVA fascinates smart interface self-adaptability, high adhesion, and outstanding self-repairing function, and then is pasted onto the interfaces of crops to deliver on the sense pesticide residue data in minimally-invasive manner, leading to the monitor of dynamic TM degradation. This study offers an in-depth penetration into dual-color wearable sensor with distinctive features for minimally-invasive monitoring pesticide residue in living crops, advancing the development of wearable crop sensors and precision agriculture.
Peroxynitrite (ONOO-) is closely associated with several pathophysiological events due to its high oxidation and nitrification reactivity, which can cause irreparable damage to a variety of biomolecules when present in excess. Consequently, the development of a reliable ONOO-detection method is essential for understanding its role. Given the significant imaging advantages of ratiometric and near-infrared (NIR) probes, a ratiometric NIR fluorescence probe (FYS) was developed for the visual detection of ONOO-both in vitro and in vivo. Probe FYS offers several benefits, including a large fluorescence emission shift (184 nm), a low detection limit (0.75 mu M), good selectivity, and rapid detection. Inspired by these outstanding characteristics, it has been successfully utilized for imaging endogenous and exogenous ONOO-in cells. More importantly, this probe could be used to monitor variations in ONOO-levels as ferroptosis progresses. We anticipate that this probe will be widely applied as a potent tool to investigate the biological function of ONOO-, thereby facilitating a deeper understanding of ferroptosis.
A Schiff base fluorescent probe (BYO) was designed and synthesized from bisphenol A. BYO fluorescent "turn-on" sensor can rapidly and simultaneously measure Al3+/Zn2+ with superior sensitivity and selectivity. Other than that, BYO exhibits enhanced fluorescence in the presence of Al3+ and Zn2+ across a wide pH range, which is resistant to interference. The detection limits were extremely low, reaching Al3+ at 9.4 × 10-9 M and Zn2+ at 4.6 × 10-8 M. The binding coefficients were calculated 8.76 × 1010 M-2 for Al3+ and 4.16 × 109 M-2 for Zn2+. Data from Job's, 1H NMR, FTIR, LC-MS, and DFT support a synergistic mechanism involving excited-state intramolecular proton transfer (ESIPT) and photoinduced electron transfer (PET). Furthermore, the BYO probe was also successfully integrated into the hydrogel to visualize and monitor the dynamic distribution and concentration changes of Al3+ and Zn2+. Moreover, characterized by high transmembrane efficiency, the BYO probe facilitates in situ detection of Al3+ and Zn2+ within living cell via fluorescence bioimaging. This work enhances the biocompatibility of fluorescent probes and expands the potential of the probes for applications in biology and smart response materials.
Excessive exposure of hypochlorite ions (ClO-) and silver ions (Ag+) lead to significant environmental safety and human health risks. How to quick and accurate detecting of Ag+ and ClO- in aquatic environment seems urgent. Continuation of preliminary work, a novel bifunctional fluorescent probe molecule of Tz.3 was designed basing on an electron donor phenothiazine core structure with intramolecular charge transfer (ICT) effect. Experimental results showed that fluorescent probe molecule of Tz.3 can rapidly detect ClO- with LOD = 2.478 nM in less 30 s and no response to Ag+ in MeOH/PBS solution. However, under UV lamp irradiation, Tz.3 can respond to Ag+ with LOD = 8.628 nM. Furthermore, the sensing mechanism of Tz.3 to ClO- and Ag+ ions were elucidated by characterization of the reaction products with UV-vis absorption, fluorescence emission spectroscopy, mass spectrometry, and DFT calculations. Finally, the colorimetric-fluorescent dual-response fluorescent probe molecule of Tz.3 was applied to detect Ag+ and ClO- ions in real water samples, and demonstrates significant potential for monitoring exogenous and endogenous ClO- in living cells.
The majority of patients with androgen-dependent prostate cancer (PCa) develop resistance to hormone therapy after approximately 18-24 months of androgen deprivation therapy treatment. During this process, PCa cells progressively lose their sensitivity to androgens and evolve into castration-resistant prostate cancer leading to uncontrolled tumor growth and ultimately the failure of endocrine therapy. To develop potential anti-prostate cancer agents, in this study, we identified a novel ether-type arylpiperazine derivative as a potent androgen receptor (AR) antagonist, uncovering a series of effective antiproliferative compounds. The derivatives (7, 11, 17, 19, 20, 21, 22, 23, and 24) demonstrated strong cytotoxicity against cancer cells, with 17, 19, 20, and 23 showing significant androgen receptor antagonistic activity (Inhibition% >60) and robust AR binding affinities. The structure-activity relationship (SAR) of these developed derivatives was discussed based on data. Docking study suggested that the compound 19 mainly bind to AR ligand binding pocket site through Van der Waals' force interactions. This research presents a promising lead compound for developing anticancer agents targeting prostate cancer therapy.
Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.
Zinc ions (Zn2+) and pyrophosphate (PPi) play pivotal roles in biological systems, with their dynamic concentrations being closely linked to various physiological and pathological processes, making them essential biomarkers for disease diagnosis and health assessment. The development of highly sensitive and selective in situ detection technologies is crucial for elucidating their biological functions. This study introduces an advanced near-infrared fluorescent sensor, DHP, constructed by integrating the molecular framework of dicyanoisophorone (DCI) derivatives with di(thiophen-2-yl)ethyl amide moieties. The probe exhibits significant aggregation-induced emission (AIE) characteristics in tetrahydrofuran/water (THF/H2O) mixed systems. Further investigations show that in THF/HEPES (1,1, v/v) buffer systems, DHP specifically recognizes Zn2+, resulting in a marked emission enhancement at 660 nm (detection limit: 0.13 μM) with a large Stokes shift of 160 nm, effectively minimizing interference from excitation light sources. Moreover, the DHP-Zn2+ complex also serves as a PPi sensor (detection limit: 0.39 μM). The sensing mechanism was investigated via 1H NMR titration experiments, Fourier transform infrared (FT-IR) spectroscopy, high-resolution mass spectrometry (HRMS) analysis, and density functional theory (DFT) calculations. Furthermore, the probe has been successfully applied in smartphone RGB detection of real water samples, portable swab tests, plant tissue Zn2+ determination, as well as imaging analysis of Zn2+ and PPi in living cells.
Ethylenediamine (EDA), a harmful and explosive industrial chemical raw material, poses significant threat to environmental and public safety. Therefore, developing portable, easy-to-use device for real-time, on-site EDA detection method is crucial. Herein, we developed a handheld EDA active detection system (EDA-HADS), incorporating an EDA-responsive solid-state sensing gel (ESSG) and an integrated air pump, as biomimetic platform for visual detection of EDA vapor in various environments. First, a Julolidine-based fluorescent probe (JDCO) with two primary amine-binding sites was designed for EDA detection, it demonstrated a rapid green-tocyan fluorescence transition to EDA with high sensitivity and specificity. JDCO was then embedded into polyacrylamide (PAM) gels to form the ESSG, enabling visual EDA vapor detection via RGB-based fluorescence color analysis. The integrated EDA-HADS, mimicking the canine olfactory system, achieved a low detection limit (LOD = 2.1 ppm) and fast response (< 120 s) to EDA, allowing on-site, quantitative EDA vapor monitoring. Moreover, the EDA-HADS design strategy employed in this work opens a new avenue for the development of artificial intelligence sensing platforms for the detection of various volatile organic compounds, thereby enhancing public safety.
Comprehensive Summary The crystallization of chiral molecules is of great significance to understand the origin and evolution of hierarchical chirality and reveal the relationships between structural chirality and circularly polarized luminescence (CPL) activity. Here, we report two pairs of chiral metal–organic frameworks (MOFs) (DCF‐17/LCF‐17, DCF‐18/LCF‐18) by utilizing tetradentate ligands tetra(3‐imidazoylphenyl)ethylene (TIPE) and 4,4'‐[4',5'‐bis[4‐(4‐pyridinyl)phenyl][1,1':2',1”‐terphenyl]‐4,4”‐diyl]bis[pyridine] (TPPP) as linkers. It can be observed that the spontaneous resolution of the achiral ligands is converted into the induced resolution, and the ligands form the absolute configuration by using enantiopure camphoric acid (cam) as chiral induced reagent (CIR). As a result, the racemate MOFs can be driven to generate absolute homochiral crystallization. Another two achiral MOFs [Cd(D‐cam)(TPPP) 0.5 ] (AF‐1, AF = achiral framework) and [Cd(L‐cam)(TPPP) 0.5 ] (AF‐2) were prepared. The position disorder of D / L ‐cam skeleton causes the generation of nonchiralization, further leading to disappearance of symmetry breaking of TPPP. For the perspective of structure, this is the first report which reveals the chiral transfer and nonchiralization between chiral induced agents and tetradentate ligands. Besides, DCF‐17 and LCF‐17 show CPL with luminescence dissymmetry factor ( g lum ) of –1.0 × 10 ‐2 and +9.2 × 10 –3 , respectively. This work provides the useful evidences to reveal the induced chiral crystallization and the construction of CPL‐active crystalline materials.
N4-acetylcytidine (ac4C) is essential for the development and migration of tumor cells. According to earlier research, N-acetyltransferase 10 (NAT10) can increase messenger RNAs (mRNAs) stability by catalyzing the synthesis of ac4C. However, little is known about NAT10 expression and its role in the acetylation modifications in prostate cancer (PCa). Thus, the biological function of NAT10 in PCa is investigated in this study. Compared to paraneoplastic tissues, the expression of NAT10 is significantly higher in PCa. The NAT10 expression is strongly correlated with the pathological grade, clinical stage, Gleason score, T-stage, and N-stage of PCa. NAT10 has the ability to advance the cell cycle and the epithelial-mesenchymal transition (EMT), both of which raise the malignancy of tumor cells. Mechanistically, NAT10 enhance the stability of high mobility group AT-hook 1 (HMGA1) by acetylating its mRNA, thereby promoting cell cycle progression to improve cell proliferation. In addition, NAT10 improve the stability of Keratin 8 (KRT8) by acetylating its mRNA, which promotes the progression of EMT to improve cell migration. This findings provide a potential prognostic or therapeutic target for PCa.