Search Results (336)

Tetracycline antibiotics are increasingly detected in aquatic environments because of their ecological risks and persistence, while conventional wastewater treatment processes are often insufficient for their effective removal from water. Here, we introduce a novel 3D graphene oxide-based nanocomposite that stacks Cu-NPs and amino-functionalized MIL-101(Fe) (denoted by Cu/NH₂-MIL-101(Fe)@GO) to effectively remove tetracycline (TC) and oxytetracycline (OTC) from environmental water samples. XPS, XRD, TEM, SEM, and FTIR analyses were conducted to characterize the structure and surface morphology of the Cu/NH₂-MIL-101(Fe)@GO nanocomposite. Overall, it was confirmed that GO, NH₂-MIL-101(Fe), and Cu-NPs were successfully incorporated, resulting in a porous material with high access to Cu-related sites as well as oxygen- and nitrogen-based functionalities (such as amino-, hydroxy-, and carboxy-groups). This hybrid system facilitates the adsorption by complementary mechanisms like surface complexation/chelation at Cu and Fe centers with the pH-dependent tetracycline species in electrostatic interactions, hydrogen bonding, π–π stacking, and molecule confinement in the metal–organic framework (MOF) pores, and by the synergistic effects at the GO–MOF(Fe)–Cu junction interfaces. The batch adsorption studies showed that the quick and efficient uptake of the two antibiotics at pH 6.5, with removal rates of 99.65–99.83%, was achieved by 15.0 mg of Cu/NH₂-MIL-101(Fe)@GO at an initial concentration of 20 ppm in 40 min at 25 °C. Equilibrium data were found to be well-fitted by the Langmuir isotherm (R² = 0.908–0.909), suggesting monolayer-dominated adsorption with the maximum capacity of 769.8–775.2 mg g⁻¹. The adsorption kinetics was well-described by the pseudo-second order model (R² = 0.9641–0.9749), which agreed with the strong binding between the tetracyclines and active sites of the nanocomposite. The main novelty of this work consists of the design of a single recoverable platform integrating GO-based preconcentration, pore accessibility of NH₂-MIL-101(Fe), and Cu-driven complexation, which led to the strong removal of tetracyclines under a relevant range of water conditions. These findings demonstrate that Cu/NH₂-MIL-101(Fe)@GO could serve as a promising high-efficiency and potentially reusable adsorbent for removing tetracycline from aqueous solution, which provides a more sustainable approach for pharmaceutical wastewater treatment. Full article

Polysialic acid (PSA), a highly negatively charged glycan attached mainly to the neural cell adhesion molecule (NCAM), is emerging as a critical but underrecognized extracellular regulator of glutamatergic neurotransmission. While previous literature has focused on PSA’s developmental roles, increasing evidence indicates that PSA–NCAM also contributes to synaptic plasticity mechanisms in the mature brain. This review integrates evidence from structural biophysics, single-channel electrophysiology, and disease models to explain how PSA modulates glutamate receptor gating to control learning and memory. We synthesize findings from biochemical reconstitution, electrophysiological recordings, and in vivo studies to show that PSA can modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor open probability, burst duration, and cooperative gating without affecting conductance, thereby promoting long-term potentiation. Conversely, PSA selectively suppresses GluN2B-containing extrasynaptic N-methyl D-Aspartate (NMDA) receptor activity by lowering open probability and calcium influx, maintaining an optimal balance between potentiation and depression while providing neuroprotection. Disruption of PSA–NCAM signaling in developmental and disease models, including prenatal cannabinoid exposure and neurodegeneration, produces cognitive deficits reversible by PSA restoration. Notably, much of the current evidence derives from in vitro systems, with relatively few studies conducted in vivo, and studies employing PSA mimetics mostly, which should be considered when interpreting physiological relevance. Collectively, the available evidence suggests that PSA functions as an extracellular modulator linking synaptic glycans to glutamate receptor regulation and plasticity related signaling pathways, highlighting the potential importance of extracellular glycan mechanisms in the control of synaptic function. Full article

Molecularly imprinted polymers (MIPs) are widely employed for selective adsorption of target molecules in sensing and separation applications. The architecture of MIP films can influence adsorption behavior, interfacial stability, and reusability, yet systematic investigations of these effects are limited. This study aimed to evaluate how different polypyrrole (PPy) MIP film architectures affect the adsorption, stability, and regeneration characteristics of geraniol-imprinted layers on gold electrodes. Geraniol-imprinted and non-imprinted PPy films were electropolymerized onto quartz crystal microbalance (QCM) substrates. Two film architectures were compared: (i) a single-layer geraniol-imprinted PPy film, and (ii) a double-layer film consisting of a non-imprinted PPy underlayer followed by a geraniol-imprinted layer. Film characterization was performed using cyclic voltammetry (CV) and electrochemical quartz crystal microbalance (EQCM) measurements. Adsorption–desorption cycles were conducted to assess mass uptake, signal stability, and regeneration performance. EQCM analysis revealed that the double-layer architecture exhibited enhanced frequency signal stability during repeated adsorption–desorption cycles compared to single-layer films, suggesting a stabilizing effect of the underlying non-imprinted PPy layer at the electrode interface. Geraniol-imprinted films demonstrated significantly higher mass uptake than non-imprinted controls, confirming the sensitivity provided by molecular imprinting. Single-layer films showed more variability in signal response and less consistent regeneration performance. The architecture of MIP films significantly affects adsorption behavior, stability, and regeneration on electrode surfaces. Incorporating a non-imprinted PPy underlayer can improve signal reproducibility and enhance the robustness of MIP-based sensing interfaces. These findings provide guidance for the rational design of MIP coatings for electrochemical sensors and QCM-active platforms. Full article

Charge transport underpins essential biological processes, including cellular respiration, photosynthesis, and enzymatic catalysis. Advances in molecular electronics have enabled single-molecule measurements that unequivocally establish redox-active proteins as efficient electron conductors, with their metal cofactors serving as intrinsic redox relays. By contrast, ubiquitous non-redox proteins lacking such redox centers have long been considered poor conductors. However, recent research has challenged this view, demonstrating that efficient charge transport in non-redox proteins can be mediated through polypeptide backbones, aromatic side-chain arrays, and hydrogen bond networks. This review surveys progress in understanding the single-molecule conductance of non-redox proteins. Firstly, we elucidate the fundamental transport mechanisms, highlighting the interplay between coherent tunneling and thermally activated hopping. We then provide an overview of state-of-the-art experimental techniques for single-molecule characterization. Through analysis of diverse systems spanning short peptides to large enzymes, we illustrate how aromatic amino acid networks and dynamic conformational fluctuations govern conductance, enabling emerging applications in label-free biosensing and single-molecule protein/DNA sequencing. Finally, we discuss persistent challenges and outline future opportunities for integrating protein-based conductors into bioelectronic devices. This review aims to stimulate further research and pave the way for novel applications harnessing protein conductance. Full article

Introduction: PMBCL is an aggressive type of lymphoma characterized by high heterogeneity in clinical, molecular, and genetic features. In PMBCL, disturbances in the NFkB pathway and deregulation of BCL-2 and mTOR family proteins are observed, which may contribute to impaired apoptosis. Therefore, many strategies have been established to target the functioning of these pathways. Early clinical trials of mTOR, NFkB and Bcl-2 inhibitors suggest their activity in many hematological cancers, but their activity as monotherapy agents may still be insufficient; therefore, combinations of these compounds with other molecules acting on those active in a given cancer subtype are being sought. Materials and Methods: In vitro studies were conducted on a single PMBCL cell line, Karpas 1106P. We administered three novel drugs: AZD2014 (vistusertib), an inhibitor of the serine-threonine kinase mTOR; IMD-0354, an NFκB inhibitor; and ABT-199 (venetoclax), a highly selective inhibitor for BCL-2. Drugs were administered alone, in pairs and in combination of all three agents. Results: Based on the results of our own research, for the Karpas cell line individually, ABT-199 had the strongest pro-apoptotic effect on cancer cells, while in pairs the most potent induction of apoptosis occurred following treatment with AZD2014+ABT-199. The combination of three drugs did not have a stronger effect than either a single drug used alone or any two-drug combination. Conclusions: These results provide preliminary in vitro evidence that targeting the BCL-2 and mTOR pathways may enhance pro-apoptotic activity in a PMBCL cell model; however, further validation in additional cell lines and in vivo models is needed before translational implications can be considered. Full article

The dangerous potential of chemical warfare requires immediate development of new materials capable of detecting and efficiently adsorbing the toxic nerve agents VX and Novichok (A-234). The current adsorbents fail to achieve sufficient detection efficiency and specific binding capabilities. Our research, conducted through advanced computational modeling, predicts that carbon nanocones (CNCs) could function as effective molecular traps for these toxic substances. The research combines density functional theory (DFT) with molecular dynamics (MD) and Monte Carlo (MC) simulations to explain the basic principles of molecular trapping by these agents. The nanocone shape produces two distinct and selective binding areas. MC shows preferential trapping VX molecules within the internal concave surface (P1), while A-234 molecules are strongly adsorbed on the external convex surface (P2). Docking results complement this by showing that A-234 exhibits stronger single-molecule binding on the more open surface, consistent with its preference for P2. The nanocone captures molecules through van der Waals forces, which produce measurable electronic changes that modify its electronic signature. The research demonstrates that carbon nanocones represent a promising candidate material for the future development of chemical defense systems, potentially including sensitive detection systems and advanced filtration technologies. Full article

Background/Objectives: Developability assessment is a critical step in advancing antibody-based molecules toward clinical application. This evaluation typically begins during clinical candidate selection and continues throughout all modifications of the molecule during development. It is guided by the target product profile, which includes the intended administration route and regimen, formulation parameters, and process conditions encountered during manufacturing, storage, and delivery. While developability testing is well established for conventional therapeutic antibodies, strategies for assessing single-domain antibodies (sdAbs) and their conjugates remain underexplored. Here, we present a strategy to test the developability of sdAbs as a case study for two clinical candidates intended as precursors for the production of diagnostic tracers for clinical imaging. Methods: Assays were developed to evaluate chemical and thermodynamic stability, target binding affinity and capacity, and chelation efficiency (“chelatability”). Accelerated stability studies were conducted for both unconjugated sdAbs and their chelator conjugated forms following incubation at two pH conditions, at multiple time points, and after twelve freeze–thaw cycles to simulate process conditions and long-term storage. Analytical assays were applied stepwise in a hierarchical approach to minimize experimental effort and material consumption. Candidates exhibiting critical developability features were selectively addressed by assays with increasing precision. Results: A tailored panel of analytical assays optimized for low molecular weight proteins was established and applied to the two clinical candidates, identifying instability hotspots as well as potential mitigation strategies. Successful engineering of a candidate with an initially critical developability profile was achieved. Conclusions: This study demonstrates the implementation of a structured developability assessment strategy for sdAb conjugates. The approach integrates physicochemical and functional stability evaluations, supporting robust candidate selection, formulation development, and method optimization for this class of molecules. Full article

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivation and excessive autoantibody production. Z-DNA binding protein 1 (ZBP1), an innate immune sensor involved in nucleic acid recognition and cell death signaling, has been implicated in antiviral and inflammatory responses. However, its role in B-cell dysregulation during SLE remains unclear. Methods: Integrative transcriptomic analyses were performed using public datasets (GSE61635, GSE235658, GSE136035, and GSE163497) to determine the expression pattern and biological functions of ZBP1 in SLE. Bulk RNA-seq and single-cell RNA-seq data were used to evaluate ZBP1 expression across B-cell subsets. Correlations between ZBP1 expression, disease activity, and immunological parameters were assessed. RNA-seq data following ZBP1 knockdown were analyzed to explore its potential downstream pathways and molecular networks. In addition, in vitro ZBP1 knockdown experiments were conducted to examine its effects on B-cell activation, plasma cell differentiation, and antibody production. Results: ZBP1 was significantly upregulated in peripheral blood and B cells from SLE patients and was enriched in pathways related to type I interferon signaling and cytokine-mediated immune responses. Single-cell transcriptomic profiling further revealed elevated ZBP1 expression across multiple B-cell subsets, including naïve B cells, memory B cells, age-associated B cells (ABCs), and plasma cells. Clinically, ZBP1 expression in peripheral B cells was positively correlated with CD86 mean fluorescence intensity (MFI), SLE Disease Activity Index (SLEDAI) scores, and serum IgG levels, suggesting a link between ZBP1 and B-cell activation. RNA-seq analysis following ZBP1 silencing demonstrated that ZBP1 regulates genes involved in the cell cycle, DNA replication, and p53 signaling, indicating its potential role in promoting B-cell proliferation and activation. Functionally, ZBP1 silencing impaired B-cell activation, reduced plasma cell differentiation, and decreased immunoglobulin production in vitro. Conclusions: Our study identifies ZBP1 as a molecule upregulated in SLE B cells and associated with B-cell activation and disease activity. Although direct causality remains to be established, the data indicate that ZBP1 may contribute to SLE pathogenesis by modulating cell cycle-related pathways and promoting aberrant B-cell responses, highlighting its potential as a biomarker and a candidate therapeutic target in SLE. Full article

Canine distemper virus (CDV) remains a highly contagious and lethal pathogen, posing a severe global threat to domestic dogs and wild carnivores. To address the urgent need for effective interventions, we utilized a proprietary Vero-SLAM cell platform to isolate a wild-type CDV strain and generate neutralizing polyclonal antibodies. Subsequently, phage display technology was employed to screen for single-chain variable fragments (scFvs) targeting the CDV hemagglutinin protein (CDV-H). This approach led to the identification of a specific scFv with virus-binding affinity comparable to commercial antibodies, which effectively blocks CDV infection in Vero-SLAM cells. Molecular docking and molecular dynamics simulations were conducted to elucidate the interaction mechanism, suggesting that this scFv binds to a novel and unique epitope on the CDV-H. These findings not only expand our understanding of the antigenic properties of the CDV H protein but also provide a theoretical foundation and a promising candidate molecule for the development of future CDV diagnostics and antiviral strategies. Full article

Alzheimer’s disease (AD) is a major public health issue, and the role of peripheral immunity in its pathogenesis remains poorly understood. This study conducted a comprehensive reanalysis of publicly available single-cell transcriptomic and chromatin accessibility datasets to investigate immune cell dynamics in AD. By integrating data from cerebrospinal fluid and peripheral blood samples, we constructed a cross-tissue immune cell atlas. Based on Monocle3 pseudotemporal trajectory analysis, we propose the hypothesis that CD8⁺ TEMRA cells in the cerebrospinal fluid may originate from blood-derived CD8⁺ TPex cells. Furthermore, cell–cell communication analysis revealed a potential interaction mechanism whereby CD8⁺ TPex cells secrete MIF signals to activate monocytes, prompting them to release increased levels of inflammatory factors (IL1B) and adhesion molecules (ICAM1). These inflammatory factors collectively contribute to the disruption of the blood–brain barrier, thereby facilitating immune cell infiltration. Our reanalysis provides a novel interpretation of existing data, establishes a regulatory framework for understanding immune infiltration in AD. Full article

Background: Colorectal cancer (CRC), with high incidence but low rates of early diagnosis, poses significant challenges to public health worldwide. Lipid metabolic reprogramming has been closely associated with CRC occurrence and development. This study aimed to identify key fatty acid metabolism-related molecules involved in the development of CRC and to explore potential prognostic biomarkers and therapeutic targets. Methods: Based on The Cancer Genome Atlas (TCGA) data from colon adenocarcinoma (COAD) patients, we applied weighted gene co-expression network analysis (WGCNA), Cox regression, and least absolute shrinkage and selection operator (LASSO) to identify fatty acid metabolism-related signature genes in CRC. Expression validation and prognostic analysis were conducted. Summary-data-based Mendelian randomization (SMR) was used to infer causal relationships between target genes and CRC. Single-cell transcriptomics and immune infiltration analysis elucidated underlying pathogenic mechanisms. Cellular and animal experiments validated tumor-suppressive effects and lipid metabolic regulatory mechanisms. Results: RPS6KA1 and CHGA were identified as fatty acid metabolism-related signature genes in COAD. Only RPS6KA1 was significantly downregulated in COAD and negatively correlated with poor prognosis (p = 0.0069). SMR confirmed its tumor-suppressive role, potentially associated with enhanced antitumor functions of CD8⁺T cells and follicular helper T cells. In vitro and in vivo experiments demonstrated that RPS6KA1 inhibits malignant progression of colon cancer and modulates fatty acid metabolism. Conclusions: Integrated multi-dimensional bioinformatic and experimental analyses reveal that RPS6KA1 remodels fatty acid metabolism and suppresses malignant progression, indicating its value as a prognostic biomarker in CRC and providing new insights for therapeutic strategies. Full article

Background: Breast cancer is one of the most frequently diagnosed cancers worldwide, with metastasis contributing to high mortality rates. Current treatments for metastatic disease are limited, emphasizing the urgent need for novel therapeutic approaches. Methods: We conducted a small-molecule drug screen utilizing patient-derived circulating tumor cells (CTCs) as a platform to identify potential anti-cancer agents. We used a dye combination and a high-content imaging microscope to evaluate cellular viability upon compound treatment. Among the 250 small molecules tested, potential hits were identified. The efficacy of these compounds was investigated using in vitro and in vivo studies in mouse breast cancer models. Bulk RNA sequencing of treated cancer cells was performed to identify differentially expressed genes, with Gene Ontology enrichment analyses conducted for their functional characterization. Results: Our screen of a 250 small-molecule library led to the identification of five hits, derivatives of meriolins known to display cyclin-dependent kinase (CDK-2/9) inhibitory activity. Subsequent in vitro and in vivo studies validated the efficacy of these compounds in inhibiting cell cycle, tumor growth, and consequently, metastatic colonization in mouse breast cancer models. Treatment with single agents (15 mg/kg) in breast cancer mouse models demonstrated good tolerability in vivo. Transcriptome profiling of treated cancer cells revealed alterations in pathways associated with cell cycle regulation, providing mechanistic insights into the anti-cancer effects of the compounds. Conclusions: By integrating drug screens, transcriptomic analysis, and in vivo validation, our study contributes to the identification of novel promising candidates for the treatment of breast cancer. Full article

The flotation efficiency of magnesite in the slurry system is critically influenced by its surface wettability. In this work, molecular dynamics (MD) and density functional theory (DFT) calculations were employed to investigate the interactions between water molecules and the magnesite (104) surface. To elucidate the underlying mechanisms, systematic evaluations were conducted, encompassing frontier orbital energies, water molecule adsorption behavior, and the water wetting process. Results indicate that electrons readily transfer from the highest occupied molecular orbital (HOMO) of water to the lowest unoccupied molecular orbital (LUMO) of magnesite. Specifically, the chemisorption of a single water molecule onto the magnesite surface was observed, with a calculated adsorption energy of −91.6 kJ/mol. This process involves an interaction between the oxygen atom of water and a surface magnesium atom, leading to the formation of an Mg–O_W bond. This bond primarily arises from hybridization between the Mg 2p, Mg 2s, and O_W 2p orbitals. Furthermore, water molecules within the first adsorbed monolayer exhibited an average adsorption energy of −66.3 kJ/mol, which further confirms the occurrence of chemisorption. Notably, minimal changes were observed in the orbital interactions between water molecules and surface Mg atoms, a trend consistent with the single-molecule adsorption case. The average adsorption energies for the second and third water layers were calculated to be −63.2 kJ/mol and −45.6 kJ/mol, respectively. The stabilization of the hydration layer structure is attributed to the hydrogen-bonding network formed among water molecules in the outer layers. As the number of water layers increases, the structural disorder of water molecules on the magnesite surface progressively intensifies. This decrease in adsorption energy with increasing layer number is attributed to the progressively enhanced contribution of hydrogen-bonding interactions between water molecules across different layers. Consequently, the magnesite surface exhibits a low contact angle, indicating high intrinsic hydrophilicity. Collectively, these findings provide molecular-level insights into the wettability of the magnesite surface, thereby contributing to a more fundamental understanding of magnesite flotation mechanisms. Full article

Aluminum nitride (AlN) possesses an exceptional combination of high thermal conductivity and an ultra-wide band gap, rendering it highly attractive for electronic packaging and semiconductor substrate applications. In this study, surface chemical modification of AlN powders was performed employing low-molecular-weight organic acids, successfully yielding hydrolysis-resistant AlN powders. The underlying mechanisms responsible for the improved anti-hydrolysis performance imparted by both single organic acids and the composite acid were systematically investigated using X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM), characterization techniques. The results reveal that Oxalic acid within the concentration range of 0.25 M to 1.50 M partially inhibits the hydrolysis of aluminum nitride (AlN); however, hydrolysis products such as aluminum hydroxide are still formed. In the case of citric acid, a higher concentration leads to a stronger anti-hydrolysis effect on the modified AlN. No significant hydrolysis products were detected when the AlN sample was treated in a 1 M aqueous citric acid solution at 80 °C. The effectiveness of the organic acids in enhancing the hydrolysis resistance of AlN follows the order: composite acid (citric acid + oxalic acid) > citric acid > oxalic acid. Under the action of the composite acid, the AlN diffraction peaks exhibit the highest intensity. Furthermore, TEM observations reveal the formation of an amorphous protective layer on the surface, which contributes to the improved hydrolysis resistance. Analytical results confirmed that the surface modification process, mediated by citric acid, oxalic acid, or the composite acid, involved an esterification-like reaction between the surface hydroxyl groups on AlN and the chemical modifiers. This reaction led to the formation of a continuous protective coordination layer encapsulating the AlN particles, which serves as an effective diffusion barrier against water molecules, thereby significantly inhibiting the hydrolysis reaction. Full article