Molecular insights into the migration of organic contaminants during purification of epoxy resin waste salt: A comparative study of interfacial wetting and ethanol/water extraction processes.

Optimizing amphipathic switching in hydrocarbon stapled peptides for enhancing endosome escape.

A dual-mode sensing platform based on bifunctional iron-doped carbon dots for sarcosine detection.

This study reports the synthesis and characterization of a novel benzimidazole-derived Schiff base (BIMPB) via the condensation of (1H-benzo[d]imidazol-2-yl)methanamine with 1-phenylbutane-1,3-dione. The structure was confirmed using 1H-NMR, 13C-NMR and FT-IR spectroscopy. Photophysical properties were extensively evaluated, revealing a strong S0 → S2 transition at 212 nm and fluorescence emission peaks at 396 and 410 nm, corresponding to π → π* and n → π* transitions. BIMPB demonstrated significant sensitivity to pH variations, exhibiting blue shifts of 11–23 nm across different environments. Furthermore, the compound acts as a fluorescent chemosensor for Cu2+ and Ca2+ ions, where coordination leads to a substantial reduction in fluorescence intensity accompanied by a distinct blue shift. The interaction between BIMPB and DNA was investigated using UV-Vis and fluorescence titration. The results showed a hypochromic effect and a minor shift in the absorption peak from 342 nm to 340 nm, suggesting a binding mechanism dominated by intercalation or electrostatic interactions. A high binding constant (Kb = 2.1 × 105 M−1) and a fluorescence quenching efficiency of 58.9% confirm the formation of a stable complex. Stern–Volmer analysis indicated a static quenching mechanism. These experimental findings, supported by molecular docking studies (binding energy = −8.3 kcal/mol), highlight the potential of BIMPB as a sensitive molecular probe for DNA-targeting and chemical sensing applications.

Design and characterization of soy protein isolate/alginate/N-doped carbon dot composite film for dual colorimetric and fluorescence sensing in intelligent packaging.

Herein, 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine (TPP-(OH)4) was functionalised with methacrylate group to convert it to a crosslinker (TPP-M) which later was used in photo-polymerisation alongside acrylamide. TPP-M obtained was characterised using proton nuclear magnetic resonance (1H-NMR), Fourier-Transform infrared (FTIR), ultraviolet-visible (UV- Vis) and fluorescence spectroscopy. The ability of TPP-M to detect Pb(II) ions was tested, and the resulted spectrum showed the reduced fluorescence intensity upon addition of Pb(II) ions. Then, the TPP-M was made into a polymer film through photo-polymerisation using UV light as a light source and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) as a photo-initiator. The film obtained was tested for Pb(II) ion detection using fluorescence spectroscopy and showed reduced fluorescence intensities.

Huntington's disease is caused by expansion of a CAG repeat in the human HTT gene, producing a mutant huntingtin protein that misfolds and forms intracellular aggregates. Although Huntington's disease is primarily characterized as a neurodegenerative disorder, mutant huntingtin is ubiquitously expressed, and peripheral tissues such as skeletal muscle exhibit pathological abnormalities. To define the muscle-intrinsic consequences of pathogenic huntingtin expression, we expressed caspase-6 truncated pathogenic human huntingtin in body wall muscle of Drosophila melanogaster larvae and performed quantitative structural and functional analyses. Aggregate analysis revealed that fluorescence intensity increased with aggregate size while aggregate morphology became more irregular. Delaying transgene expression until later stages of larval development dramatically reduced aggregate number, demonstrating a strong temporal dependence of aggregate formation. Myonuclei were enlarged, misshapen, and exhibited significantly reduced fluorescence intensity, consistent with altered chromatin organization. Notably, huntingtin aggregates were observed within the nucleus, indicating that nuclear proteostasis is directly perturbed by pathogenic huntingtin in muscle cells. Despite these intracellular defects, muscle fiber shape and sarcomere organization were preserved, suggesting that contractile apparatus assembly is not overtly disrupted. In contrast, mitochondrial organization was severely affected, with extensive mitochondrial aggregation throughout muscle fibers, consistent with altered organelle homeostasis. Functional analyses demonstrated that pathogenic huntingtin expression significantly impaired neuromuscular performance. Larvae exhibited reduced excitatory junctional potentials and diminished muscle contractile force, indicating compromised synaptic transmission and muscle function. Together, these findings demonstrate that pathogenic human huntingtin expression in skeletal muscle is sufficient to drive widespread protein aggregation, nuclear and mitochondrial abnormalities, and functional deficits despite the absence of overt structural changes. Our results highlight the importance of muscle-intrinsic pathogenic mechanisms and provide a quantitative framework for understanding how mutant huntingtin disrupts cellular organization and physiology outside the nervous system.

Sishen Wan suppresses colon cancer through dual inhibition of PI3K/AKT/mTOR and STAT3-mitophagy pathways: Network pharmacology and experimental validation.

Structurally optimized photo-crosslinkable casein-PEG hydrogels for enhanced encapsulation and functional stability of resveratrol.

Background: Brugada syndrome (BrS) is a genetic cardiac arrhythmia disorder inherited in an autosomal dominant manner, characterized by ST-segment elevation in the right precordial leads (V1-V3) on electrocardiograms (ECGs). This syndrome predominantly affects young individuals with structurally normal hearts and significantly increases the risk of ventricular arrhythmias and sudden cardiac death (SCD). The most common genotype found among BrS patients is caused by variants in the SCN5A gene, which lead to a loss of function of the cardiac sodium channel Nav1.5 by different mechanisms. Methods: Plasmids containing SCN5A were constructed using PCR and site-directed mutagenesis to create the D372H variant. HEK293 cells were cultured and transfected with the WT, D372H, or a combination of both plasmids. Patch-clamp recordings assessed sodium current characteristics. Confocal microscopy visualized channel localization. Quantitative RT-PCR was used to analyze mRNA expression levels, while Western blot evaluated protein expression using specific antibodies. Results: In HEK293 cells expressing the D372H mutant, functional assays revealed a near-complete loss of sodium currents. Co-transfection of WT and D372H plasmids resulted in a significant reduction in current density compared with WT alone, while activation, inactivation, and recovery kinetics were unaffected. In addition, both the mutant protein and protein expressed in co-transfected cells exhibited reduced fluorescence intensity, indicating decreased expression levels. These findings were further supported by Western blot and RT-qPCR analyses. Conclusions: In summary, our findings indicate that the D372H variant produces a marked reduction in Nav1.5 function through reduced sodium current density and decreased channel expression. Given its critical position within the DI-pore loop, this defect is expected to markedly diminish the inward sodium current necessary for normal depolarization. Such impaired excitability-particularly relevant in the right ventricular outflow tract-may accentuate regional differences in repolarization and create conditions that favor reentrant activity. These findings provide mechanistic insights into how the p.D372H variant alters Nav1.5 channel function in vitro and offer functional evidence that may assist in interpreting its potential relevance to Brugada syndrome.

BACKGROUND:Acquired resistance to BRAFV600E inhibitors remains a major obstacle in melanoma treatment. We hypothesized that melanoma-initiating cells (MICs), regulated by cancer-associated fibroblasts in the tumor microenvironment, mediate drug resistance through stromal Notch1 signaling.STUDY DESIGN:Patient-derived melanoma-associated fibroblasts (MAFs) were engineered to activate Notch1 signaling (MAFN1IC-GFP) via lentiviral transduction. Drug resistance was assessed using BRAF inhibitor-resistant melanoma cells (451LuBR) in 3-dimensional spheroid co-culture assays with PLX4720 treatment. In vivo efficacy was evaluated in NOD scid gamma mice cografted with 451LuBR cells and MAFN1IC-GFP or control MAFGFP (n = 8/group). Primary endpoints included tumor growth, angiogenesis, and CD271⁺ MIC populations assessed by immunofluorescence and quantitative imaging.RESULTS:In vitro, MAFN1IC-GFP suppressed drug-resistant melanoma spheroid formation across PLX4720 concentrations (1 to 100 μM, p < 0.01). In vivo, MAFN1IC-GFP cografting reduced tumor growth by 50% (mean tumor weight, p < 0.01) and bioluminescence signal (p < 0.05). Mechanistically, MAFN1IC-GFP selectively depleted CD271⁺ MICs (~50% reduction in fluorescence intensity, p < 0.01), decreased their proliferation (p < 0.01), and induced apoptosis (p < 0.01).CONCLUSIONS:Activating Notch1 signaling in MAFs overcomes BRAF inhibitor resistance by disrupting cancer stem cell niches. This stromal-targeted approach represents a novel therapeutic strategy to complement surgical and systemic therapies in melanoma patients with drug-resistant disease.

Natural soy protein isolate (SPI) exhibits suboptimal functional characteristics, including limited solubility, reduced foaming capacity, and diminished emulsifying ability. Conventional singular-modification techniques are unable to enhance multiple functional properties concurrently, thereby posing challenges in fulfilling the varied requirements of food processing. Therefore, this study employed ultrasonic and pepsin enzymatic modification techniques on SPI. By varying ultrasonic frequency (20 kHz, 207 kHz) and sonic energy density (295 W/L, 590 W/L), different modified protein samples were obtained. The effects of single treatment, combined treatment, and varying ultrasonic parameters on their structure and functionality were investigated. The results indicate that compared to single enzymatic hydrolysis, combination-treated SPI exhibited reduced fluorescence intensity and UV absorbance, along with significant decreases in methionine (Met) and free-sulfhydryl (SH) content (p < 0.05). Particle size decreased while distribution became more uniform, and relative molecular weight also diminished. This indicates that combined processing induces more pronounced changes in the protein's primary to higher-order structures, thereby enhancing functional properties. Specifically, surface hydrophobicity (H0) and emulsification stability (ESI) improved, while emulsifying capacity (EAI) significantly increased (p < 0.05). In summary, ultrasonication combined with enzymatic hydrolysis exhibits synergistic effects, optimizing protein structure and functional characteristics. This approach facilitates the development of functional foods and broadens their application scope.

Reduction in fluorescence intensity upon addition of quencher molecules is often quantified by the Stern-Volmer equation. Central to the underlying model is the formation of an adduct between quencher and excited state (dynamic quenching), or ground-state (static quenching), fluorophore at steady-state conditions. Assuming a thermodynamic behavior, that is, a system with large numbers of fluorophore and quencher molecules, the resulting dependency of the ratio between fluorescence intensities, with and without quencher, on quencher's concentration is linear. Yet, alongside abundance reports confirming this linear behavior, numerous observations indicate the dependency can also be nonlinear with either upward or downward curvature. By maintaining the same physical mechanisms for quenching, we derive in this paper an alternative equation to describe fluorescence quenching. Here, however, we assume a local equilibrium (steady-state) between a single fluorophore and a finite number of surrounding quencher molecules, effectively partitioning the (macroscopic) system into many noninteracting small subsystems. Depending on the fluorophore's properties, the association's strength, and conditions, the resulting behavior exhibits linear dependencies, upward curvatures, or downward curvatures. More specifically, the relation reads, , where K is a steady-state equilibrium constant for complex formation and [Q] T is the total concentration of quencher in the small subsystem. The dimensionless parameter has different expressions for dynamic and static mechanisms. In the former, it is a ratio between the maximum rate of quenching and the rate of fluorophore excitation, whereas in the latter, it is a function of the fraction of excited fluorophore. Intriguingly, this relation applies also for systems with exciplex emissions. We tested the validity of this model on 151 experimental fluorescence quenching plots, taken from the literature, operated by dynamic, static, and combined mechanisms. The results of the fitting are excellent with an average correlation coefficient of 0.9985.

CH3/CF3 substituent dependent tunable fluorescence and thermofluorochromism triphenylamine-acetophenone fluorophore.

Colorimetric/fluorescent dual-channel ammonia-responsive films based on sodium alginate and polyvinyl alcohol for monitoring freshwater shrimp freshness.

Breast cancer is a widespread and aggressive disease, with 2.3 million new cases globally in 2022. Metastasis, the spread of cancer cells to distant organs, remains a leading cause of breast cancer-related mortality. Current treatment options, particularly traditional chemotherapeutic drugs, are often associated with severe side effects, emphasizing the urgent need for safer and more effective therapeutic alternatives. Triple-negative breast cancer (TNBC) represents one of the most aggressive breast cancer subtypes, characterized by the absence of estrogen receptors (ER), receptors (PR), and HER2 expression. The human TNBC cell line MDA-MB-231, was selected in this study due to its aggressive, metastatic phenotype and its well-established use in zebrafish xenograft models. This makes it a highly relevant platform for preliminary in vivo evaluation of novel plant-derived compounds, particularly those targeting hard-to-treat breast cancer subtypes such as TNBC. Elaeagnus angustifolia (EA), commonly known as Russian olive, has attracted interest for its antimicrobial, anti-inflammatory, and antioxidant properties. However, its potential anticancer activity, especially against TNBC, remains relatively unexplored. This research investigated the efficacy of EA extract against MDA-MB-231 TNBC cells using a wild-type AB zebrafish model. A key objective was to evaluate the toxicological profile of EA across multiple physiological parameters in zebrafish, including developmental, cardiovascular, neuromuscular, and hepatic functions. The study identified safe, non-toxic concentrations of EA extract (0.5 mg/mL and 0.75 mg/mL). Moreover, treatment with EA in zebrafish xenografts led to a dose-dependent reduction in fluorescence intensity of injected TNBC cells, suggesting suppression of tumor cell proliferation and survival.. These findings suggest that EA warrant further investigation as a potential anticancer agent for TNBC. The observed safety profile and preliminary anti-tumor effects in zebrafish provide a foundation for future mechanistic and mammalian studies.

Intracerebral hemorrhage (ICH) incidence increases with age, and neuronal mitochondrial dysfunction and apoptosis post-ICH contribute to severe secondary brain injury. It is of paramount importance to explore molecular targets for protecting against brain injury after ICH. UBA52, a ubiquitin precursor protein, was found to be upregulated in brain tissues of ICH mice. Intracerebral injection of adeno-associated virus type 9 overexpressing UBA52 (AAV9-UBA52) alleviated neurological deficits and brain edema in ICH mice. In vitro and in vivo experiments demonstrated that UBA52 overexpression reduced hemin or ICH-induced apoptosis, reflected in decreased TUNEL-positive cells and reduced caspase-3 and caspase-9 levels. The augmentation of fluorescence intensity in Mitotracker labeling and the reduction of fluorescence intensity in JC-1 staining suggested that UBA52 overexpression mitigated hemin-induced mitochondrial damage. This was further evidenced by increased cellular ATP content and elevated cytochrome c levels located in mitochondria. In vivo findings showed that UBA52 overexpression reduced the quantity of degenerative neurons. UBA52 and NeuN co-localization verified its direct protective effect on neurons. IP-LC/MS and Co-IP assays identified Daxx as a UBA52-interacting protein, with UBA52 promoting Daxx ubiquitination and degradation. Rescue experiments showed Daxx overexpression abolished the protective effect of UBA52 against hemin-induced apoptosis and mitochondrial dysfunction. Collectively, this study demonstrated that UBA52 ameliorates ICH-induced secondary brain injury by promoting Daxx ubiquitination/degradation to inhibit neuronal apoptosis and mitochondrial damage, suggesting UBA52 as a potential protective target for ICH therapy.

The photophysical properties of thioanisole (SCH3) and its derivatives as a representative system for investigating aryl sulfides were explored by TD-DFT using the B3LYP functional. Thioanisole appears in a variety of chemical applications due to its structural and reactive properties such as in dyes, drugs, and materials. Our investigations focus on the structural, photophysical, and dynamic properties influenced by substituents (F and Cl) on absorption and emission spectra. The electronic transition mainly corresponds to S₀→S₂ (π→σ*) with excitation energies of 5.11 eV and 5.02 eV for SCH₃F and SCH₃Cl, respectively. The dynamic simulations on the first-excited state provide additional insights that complement those obtained from static calculations. The fluorescence spectrum of SCH3F typically shows a blue shift, while the fluorescence spectrum of SCH3Cl displays a red shift compared to SCH3. These findings indicate that the inductive effect plays a crucial role in structural stability, particularly influencing internal conversion during the dynamics, which may lead to a reduced fluorescence intensity.

The bone marrow (BM) niche plays a pivotal role in regulating the fate of hematopoietic stem cells (HSCs), and its integrity changes significantly during aging and in rare hematological disease, as in myelofibrosis (MF). In this study, we investigated how the localization and dynamics of HSCs are influenced under physiological and pathological conditions by a newly identified by HSC-supportive megakaryocytes (MKs) subpopulation. Using huCD34tTA/TetO-H2BGFP reporter mice, we analyzed HSCs distribution within the BM and quantified nuclear green fluorescent protein (GFP) intensity to assess the repopulating potential of aged controls and mutated Gata1low mice for MF. In the control group of aged mice, cells with high levels of GFP are clustered, and adjacent to cells morphologically identifiable as supportive MKs. These clusters displayed homogeneous GFP intensity, indicating that HSCs with similar functional properties tend to co-localize in proximity to supportive MKs. By contrast, in aged huCD34/TET/Gata1low mice, GFP cells were predominantly isolated and showed reduced fluorescence intensity. Although the frequency of MKs with a supportive phenotype was increased in MF mice, analyses of GFP revealed that the ability of these MKs to maintain the HSCs in their niche was significantly impaired. Our results provide new insights on the maladaptive remodeling of the BM niche. They highlight the supportive role of MKs as potential key regulators of HSCs homeostasis. Despite their numerical expansion in MF, these cells are functionally compromised, thereby contributing to altered HSCs localization, mobilization, and to hematopoietic failure.

Effects of dry-heating time on the physicochemical properties of abalone myofibrillar protein-polysaccharide conjugates and the antioxidant activity of their in vitro digestion products.