Search Results (346)

Alzheimer’s disease (AD) is a progressive, complex, multifactorial, neurodegenerative disease and accounts for most cases of dementia. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and monoclonal antibodies. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis, having only symptomatic effects. Thus, the priority remains prevention and clarifying AD etiology. A better understanding of the neuroprotective mechanisms undertaken by specific genes is crucial to guide the design of novel therapeutic agents via selective ligands and precision medicine. In this review, we present a perspective of the physiological phase of the AD spectrum, of risk factors in AD with a focus on therapeutic approaches in three categories: neurotransmitters/ion modulations, peptide deposit control and aspecific treatments, followed by a discussion of treatment limitations. An overview of innovative strategies and non-pharmaceutical ancillary support is given. Full article

The deep defluorination of water remains a significant environmental challenge. In this work, aluminum was loaded onto the bifunctional resin S957 containing a phosphoric-sulfonic acid difunctional group for efficient fluoride removal. Al-S957 demonstrated excellent fluoride removal performance across a broad pH range. When anions and organics coexisted, Al-S957 exhibited significantly better fluoride adsorption performance compared to aluminum-loaded monofunctional resins. The adsorption followed an endothermic chemisorption process on a monolayer surface. FTIR and XPS analyses further revealed that fluoride removal relied on a ligand exchange mechanism. Column adsorption conducted over five cycles highlighted the strong practical potential of Al-S957. The results suggested that Al-S957 exhibits significant potential for practical applications. Full article

Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals widely used in industrial applications and have become persistent environmental contaminants due to their chemical stability. Water-soluble PFASs with fewer than ten carbon atoms, such as perfluorooctanoic acid (PFOA), are particularly concerning because of their high solubility in water, environmental mobility, and resistance to degradation. In this work, we present an eco-friendly Fe₃O₄ magnetic nanoparticle (MNP)-based platform for the detection and removal of PFOA from water. The synthesized iron oxide MNPs exhibit rapid and strong magnetic responsiveness, enabling efficient magnetic separation for both PFOA detection and removal. To optimize surface affinity for PFOA, we functionalized the MNPs with distinctive ligands, including polyethylene glycol (PEG), β-cyclodextrin (βCD), and dopamine (DA). Among these, PEG and DA showed notable binding affinity toward PFOA, as confirmed by infrared spectroscopy and colorimetric assays. After incubation with the functionalized MNPs followed by magnetic retrieval, we achieved over 90% PFOA removal efficiencies, demonstrating the potential for future research in PFAS remediation technologies. Importantly, the system was validated using deionized, tap, and lake water, all of which yielded comparable and promising results. This study provides a promising, eco-friendly, and recyclable nanomaterial platform for investigating the crucial role of surface chemistry in nanoparticle–PFAS interactions through ligand-mediated magnetic separation. Full article

In recent years, extensive attention has been paid to advanced oxidation processes (AOPs) with peracetic acid (PAA), a widely used disinfectant, using transition metal ions for the degradation of organic contaminants within water environments. Mn(II) has been widely used as an effective homogeneous transition metal catalyst for oxidant activation, but it has shown poor performances with PAA. Since the stability of manganese species can be enhanced through the addition of ligands, this study systematically investigated a novel AOP for the oxidation of carbamazepine (CBZ) using an Mn(II)/PAA system with several different ligands added. The reactive species were explored through UV-vis spectrometry, scavengers, and probe compounds. The results suggest that Mn(III)–ligand complexes and other high-valent Mn species (Mn(V)) were generated and contributed obviously toward efficient CBZ oxidation, while radicals like CH₃CO₂^• and CH₃CO₃^• were minor contributors. The oxidation efficiency of Mn(II)/PAA/ligands depended highly on ligand species, as ethylene diamine tetraacetic acid (EDTA) and oxalate (SO) could promote the oxidation of CBZ, while pyrophosphate (PPP) showed modest enhancement. The results obtained here might contribute to the removal of residue pharmaceuticals under manganese-rich waters and also shed light on PAA-based AOPs that could help broaden our present knowledge of manganese chemistry for decontamination in water treatment. Full article

Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The CD36 gene is alternatively spliced. It has several alternative promoters and first exons. The alternative transcripts are expressed in multiple tissues, and their expression patterns are highly variable. The molecular mechanisms that regulate CD36 gene expression are complex and reflect its multifunctional role in different tissues. CD36 activity has been linked to several metabolic processes, such as inflammation, angiogenesis, phagocytosis, and energy homeostasis. CD36 plays a key role in regulating vascular and cardiovascular health and in the pathogenesis of atherosclerosis. CD36 gene mutations in the Caucasian population are rare. Hence, it is extremely difficult to recruit a statistically significant group of CAD patients with these mutations. Nevertheless, this population is largely at risk of cardiovascular disease. Atherosclerosis is a multifactorial disease, but the role of the CD36 receptor in the development of ox-LDL is extremely important. This review aims to introduce readers to issues related to the relationship between CD36 and CAD. The activity of this receptor should be considered when exploring treatment options for atherosclerosis-related complications. Full article

With the worsening global water pollution crisis, pharmaceuticals and personal care products (PPCPs) have been increasingly detected in aquatic environments. The effective removal of PPCPs remains challenging for conventional water treatment technologies, whereas photocatalytic technology has shown distinct promise. Dissolved organic matter (DOM), a ubiquitous component of aquatic ecosystems, exerts multifaceted effects on the photocatalytic oxidation of PPCPs. In this article, the influence of DOM on the performance of various photocatalysts in PPCP removal is systematically summarized and analyzed. This review highlights DOM’s role in altering the migration and transformation of PPCPs via processes including adsorption and complexation. The adsorption of PPCPs on photocatalysts is achieved by competitive adsorption or by providing more adsorption sites. DOM modifies the structural properties of photocatalysts through mechanisms such as ligand exchange, intermolecular forces, electrostatic forces, and hydrophobic interactions. DOM inhibits the formation of active species via light attenuation and shielding effects while simultaneously enhancing their generation through photosensitization and electron transfer facilitation. In this review, the interaction mechanism among DOM, PPCPs, and photocatalysts within the PPCP photocatalytic oxidation system is expounded on. These findings provide novel insights into optimizing photocatalytic reaction conditions and enhancing treatment efficiency, while providing a theoretical foundation for advancing efficient, eco-friendly PPCPs remediation technologies. Full article

Ubiquitin-specific protease 7 (USP7), a deubiquitinase enzyme responsible for removing ubiquitin (Ub) from target proteins, plays a crucial role in oncogenic pathways and has been implicated in various human diseases. X-ray crystallography has revealed distinct conformations of USP7, including apo (ligand-free), allosteric inhibitor-, and Ub-bound states. However, the dynamic mechanisms underlying the allosteric inhibition of USP7 remain unclear. This study investigates the effect of allosteric inhibitor binding on the dynamics of USP7 through multiple replica molecular dynamics simulations. Our results demonstrate that Ub binding stabilizes the USP7 conformation, while allosteric inhibitor binding increases flexibility and variability in the fingers and palm domains of USP7. Furthermore, our analysis of USP7 local regions reveals that allosteric inhibitor binding not only restrains the dynamics of the C-terminal Ub binding site, thereby impeding the accessibility of Ub to USP7, but also disrupts the proper alignment of the catalytic triad (Cys223-His464-Asp481) in USP7. Additionally, community network analysis indicates that intra-domain communications within the fingers domain in USP7 are significantly enhanced upon allosteric inhibitor binding. This study reveals that the binding of an allosteric inhibitor induces a dynamic shift in enzyme’s conformational equilibrium, effectively disrupting its catalytic activity through allosteric modulation. Full article

Accurately predicting protein–ligand binding affinity is an important step in the drug discovery process. Deep learning (DL) methods have improved binding affinity prediction by using diverse categories of molecular data. However, many models rely heavily on interaction and sequence data, which impedes proper learning and limits performance in de novo applications. To address these limitations, we developed a novel graph neural network model, called StructureNet (structure-based graph neural network), to predict protein–ligand binding affinity. StructureNet improves existing DL methods by focusing entirely on structural descriptors to mitigate data memorization issues introduced by sequence and interaction data. StructureNet represents the protein and ligand structures as graphs, which are processed using a GNN-based ensemble deep learning model. StructureNet achieved a PCC of 0.68 and an AUC of 0.75 on the PDBBind v.2020 Refined Set, outperforming similar structure-based models. External validation on the DUDE-Z dataset showed that StructureNet can effectively distinguish between active and decoy ligands. Further testing on a small subset of well-known drugs indicates that StructureNet has high potential for rapid virtual screening applications. We also hybridized StructureNet with interaction- and sequence-based models to investigate their impact on testing accuracy and found minimal difference (0.01 PCC) between merged models and StructureNet as a standalone model. An ablation study found that geometric descriptors were the key drivers of model performance, with their removal leading to a PCC decrease of over 15.7%. Lastly, we tested StructureNet on ensembles of binding complex conformers generated using molecular dynamics (MD) simulations and found that incorporating multiple conformations of the same complex often improves model accuracy by capturing binding site flexibility. Overall, the results show that structural data alone are sufficient for binding affinity predictions and can address pattern recognition challenges introduced by sequence and interaction features. Additionally, structural representations of protein–ligand complexes can be considerably improved using geometric and topological descriptors. We made StructureNet GUI interface freely available online. Full article

MIL-101(Cr), a widely studied chromium-based metal–organic framework material consisting of chromium metal ions and terephthalic acid ligands, has attracted much attention due to its ultra-high specific surface area, large pore size, and excellent thermal, chemical, and aqueous stability. The outstanding properties and abundant unsaturated Lewis acid sites of this material have shown promising applications in aqueous phase adsorption, gas storage, separation, catalysis, drug delivery, and sensing. In this paper, we systematically review the synthesis technology and performance optimization strategy of MIL-101(Cr), discuss the advantages and limitations of various synthesis methods, such as traditional hydrothermal method, microwave-assisted hydrothermal method, template method, and solvent-thermal method, and summarize and analyze the optimization strategy of MIL-101 from the aspects of physical modification and chemical modification. In addition, this paper summarizes the latest application progress of MIL-101(Cr) in gas adsorption and separation, wastewater purification, pollutant removal, catalysis, and pharmaceutical delivery, and points out the current challenges and future development directions, to provide guidance and inspiration for the industrial application of MIL-101(Cr) and the development of new materials. Full article

To address the challenges of environmental adaptability and passivation in nanoscale zero-valent iron (nFe⁰) systems, we developed oxalate-modified nFe⁰ (nFe_oxa) through a coordination-driven synthesis strategy, aiming to achieve high-efficiency Cr(VI) removal with improved stability and reusability. Structural characterization (STEM and FT-IR) confirmed the formation of a FeC₂O₄/nFe⁰ heterostructure, where oxalate coordinated with Fe(II) to construct a semiconductor interface that effectively inhibits anoxic passivation while enabling continuous electron supply, achieving 100% Cr(VI) removal efficiency within 20 min at an optimal oxalate/Fe molar ratio of 1/29. Mechanistic studies revealed that the oxalate ligand accelerates electron transfer from the Fe⁰ core to the surface via the FeC₂O₄-mediated pathway, as evidenced by EIS and LSV test analyses. This process dynamically regenerates surface Fe(II) active sites rather than relying on static-free Fe(II) adsorption. XPS and STEM further demonstrated that Cr(VI) was reduced to Cr(III) and uniformly co-precipitated with Fe(II/III)-oxalate complexes, effectively immobilizing chromium. The synergy between the protective semiconductor layer and the ligand-enhanced electron transfer endows nFe_oxa with superior reactivity. This work provides a ligand-engineering strategy to design robust nFe⁰-based materials for sustainable remediation of metal oxyanion-contaminated water. Full article

ADAMTS-5 (aggrecanase-2) is a major metalloprotease involved in regulating the cartilage extracellular matrix. Due to its role in removing aggrecan in the progression of osteoarthritis (OA), ADAMTS-5 is often regarded as a potential therapeutic target for OA. Punicalagin (PCG), a polyphenolic ellagitannin found in pomegranate (Punica grunatum L.), and ellagic acid (EA), a hydrolytic metabolite of PCG, have been widely investigated as potential disease-modifying osteoarthritis drugs (DMOADs) due to their potent antioxidant and anti-inflammatory properties, but their interaction with ADAMTS-5 has yet to be determined. In this study, molecular docking simulations were used to predict enzyme–inhibitor binding interactions. The results suggest that both compounds may be able to bind within the active site via the formation of H bonds and interactions between the ligand’s aromatic rings and hydrophobic residue in the enzyme with inhibition constants of 183.3 µM and 1.13 µM for PCG and EA, respectively. Biochemical activity against recombinant human ADAMTS-5 was assessed using a dimethylmethylene blue-based assay to determine residual sulfated glycosaminoglycan (sGAG) in porcine articular cartilage. Although its loss could not be attributed to ADAMTS-5, sGAG was effectively persevered by PCG and EA. The potential conversion of PCG to EA by enzyme-catalyzed hydrolysis activity was then investigated using liquid chromatography–mass spectroscopy to determine the potential for the use of PCG and EA as a prodrug–proactive metabolite pair in the development of drug delivery systems to arthritic synovial joints. Full article

Excessive phosphorus discharge from fertilizers and detergents has caused severe eutrophication in water bodies, necessitating the upgrading of efficient and cost-effective adsorbents for phosphorus removal. In this study, a novel lanthanum and extracellular polymeric substance (EPS) coprecipitation-modified ceramic (La-EPS-C-450) was developed to address the limitations of existing adsorbents. The ceramic filler served as a robust and scalable matrix for lanthanum loading, while EPS introduced functional groups and carbonate components that enhanced adsorption efficiency. The prepared adsorbent manifested a maximum phosphorus adsorption capacity of 83.5 mg P/g-La at 25 °C, with its performance well expressed by the Freundlich isotherm model, indicating that it was a multilayer adsorption process. The adsorption mechanism was driven by electrostatic attraction and ligand exchange between lanthanum and phosphate ions, forming inner-sphere complexes. The material demonstrated unfluctuating‌ performance across a pH range of 3–7 and retained high selectivity in the presence of competing anions. In practical applications, La-EPS-C-450 effectively removed phosphorus from actual river water, achieving a treatment capacity of 1800 bed volumes in a continuous-flow fixed column system. This work provides valuable insights into the progress of advanced ceramic-based adsorbents and demonstrates the potential of La-EPS-C-450 as a cost-efficient and effective material for phosphorus removal in water treatment applications. Full article

A facile method was employed to impregnate activated carbon, a commonly used water treatment medium, with nanostructured magnesium oxide for fluoride removal. Batch adsorption tests were conducted to evaluate the adsorption performance of the nanostructured magnesia-impregnated activated carbon (nMgO@AC) for fluoride removal. The results demonstrated that this composite material exhibited a good adsorption capacity, with a maximum equilibrium uptake of approximately 121.1 mg/g for fluoride. Kinetic studies revealed that the adsorption process followed the pseudo-second-order adsorption kinetic model, reaching equilibrium in about 100 min. Within the initial pH range of 3 to 11, the adsorption efficiency of nMgO@AC for fluoride remained above 95%, indicating that the initial solution pH had a minimal effect on the material’s fluoride removal capability. The adsorption mechanism was elucidated by characterizing the material properties before and after adsorption using SEM, TEM, XRD and XPS. Initially, magnesium oxide reacted with water and rapidly transformed into magnesium hydroxide. Subsequently, a ligand exchange occurred between the hydroxide groups in magnesium hydroxide and fluoride ions in the aqueous solution, resulting in the effective removal of fluoride. The findings of this study suggest that nanostructured magnesia-impregnated activated carbon holds significant potential for the treatment of fluoride-containing wastewater, particularly for highly alkaline wastewater. Full article

The excessive levels of neonicotinoid insecticides, particularly thiacloprid (THI), in the environment have become a significant threat to ecosystems. This study investigates the catalytic degradation of THI using pinewood biochar (PBC), zero-valent iron (ZVI), and ZVI/PBC composite, with a particular focus on the reaction activity modulation mediated by organic acids (humic acid: HA and oxalic acid: OA). Reductive dechlorination dominated THI degradation as observed by Cl⁻ release kinetics. Compared to HA (39.73%), the OA (73.44%) addition markedly increased the THI removal efficiency by ZVI/PBC, which alone has a lower removal efficacy, i.e., 37.29%. The increase in the THI removal rate was attributed to its enhanced electron transfer capacity. As confirmed by electrochemical characterization, the addition of organic acids promotes electron transfer between THI and catalysts (ZVI, PBC, or ZVI/PBC), thereby improving the removal efficiency of THI. XRD/XPS analyses elucidated that OA preferentially converted passivating Fe₂O₃/Fe₃O₄ on ZVI/PBC to reactive FeOOH and formed electron-conductive Fe–COO bonds, thereby suppressing oxide layer formation. PBC amplified these effects through ZVI dispersion and electron shuttling, reducing aggregation-induced activity loss. These findings provide a mechanistic framework for optimizing ligand-engineered iron composites, offering practical strategies to enhance pesticide remediation efficiency in organic acid-rich environmental systems. Full article

This study investigated the effectiveness of a ligand known as (2-Mercapyo-phenylimino)-1,3-dihydro-indol-2-one-based ligand, in removing stable/radioactive cesium and cobalt from contaminated wastewater. Several parameters, such as contact duration, temperature, adsorbent quantity, pH of the medium, and concentration of adsorbate, have been investigated as primary active parameters impacting the adsorption process. Regarding the stable isotopes, the concentrations of Co²⁺ and Cs⁺ were measured before and after the treatment processes using the Optical Emissions Spectroscopy with Inductively Coupled Plasma (ICP-OES) technique. Additionally, kinetic and equilibrium isotherm models were applied to understand the equilibrium data. Both Cs⁺ and Co²⁺ were ideally eliminated after 120 and 60 min, respectively. The optimal pH for Cs⁺ was 6.3, while that for Co²⁺ was 5. The results indicate that the adsorption process is endothermic for Co²⁺ and exothermic for Cs⁺. Three thermodynamic parameters (∆G°, ∆H°, and ∆S°) were calculated. The reported R² values for the Freundlich and Langmuir models showed that the adsorption process for Cs⁺ and Co²⁺ always followed these isotherms, regardless of the temperature used. For Cs⁺, the maximum single-layer capacity (q_max) was 15.10 mg g⁻¹, while for Co²⁺, it was 62.11 mg g⁻¹. When the aqueous medium was spiked with both radioisotopes individually, the elimination of ⁶⁰Co and ¹³⁴Cs achieved maximum values of 99 and 86%, respectively, within 120 min. It can be concluded that the ligand effectively removed cobalt and cesium from wastewater, with higher adsorption for cobalt. Full article