Major Binding Research Articles

Developing alkali-activated controlled low-strength material (CLSM) using urban waste glass and red mud for sustainable construction

Using industrial waste in controlled low-strength material (CLSM) offers many benefits and addresses waste management issues. However, identifying optimal CLSM design while balancing environmental impacts and engineering properties poses a notable challenge. Herein, new alkali-activated CLSM formulations based on urban waste glass and red mud (RM) are proposed for the first time with systematic investigations into the material properties and sustainability. The formulations involve the ternary blends of slag, glass powder (GP) and RM as the binders and crushed glass as aggregate. Our observations show RM has a clay-like texture with complex crystalline phases rich in Al and Fe. Increasing the proportion of RM to GP notably decreases the flowability, extends the setting time and impairs the mechanical properties. Nevertheless, red mud demonstrates a crucial role of reducing bleeding level especially for the mixtures with high proportions of glass aggregate. The standard leachate tests as per toxicity characteristic leaching procedure (TCLP) show the heavy metals leached from the CLSM are below the concentration limits and exhibit low mobility. The microstructural and thermodynamic analyses reveal the precipitation of calcium-(sodium-)aluminosilicate hydrate (C-(N-)A-S-H) as the major binding material. The reactive Fe and Al in red mud most probably contribute to the formation of hydrogarnet phases. Moreover, the suggested CLSM formations typically exhibit reduced carbon emissions and lower costs compared to the traditional CLSM produced with cement and fly ash, underlining their environmental sustainability and cost-effectiveness. This study provides a potential guideline for the flowable fill construction in the regions with bauxite producers.

Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens.

The opportunistic pathogen Pseudomonas aeruginosa develops increasing resistance toward even the most potent antibiotics. Like other bacteria, the pathogen produces a number of virulence factors including metallophores, which constitute an important group. Pseudomonads produce the iron-chelating metallophore (siderophore) pyochelin, which, in addition to its iron-scavenging ability, is an effector for the transcriptional regulator PchR in its FeIII-bound form (ferripyochelin). In the present study, docking studies predicted a major ferripyochelin binding site in PchR, which prompted the exploration of nor-pyochelin analogues to produce tight binding to PchR, and thereby upregulation of the pyochelin metabolism. In addition, we investigated the effects of using the analogues to bind the antimicrobial cations GaIII and InIII. Selected analogues of nor-pyochelin were synthesized, and their GaIII- and InIII-based complexes were assessed for antimicrobial activity. The results indicate that the GaIII complexes inhibit the pathogens under iron-limited conditions, while the InIII-based systems are more effective in iron-rich media. Several of the GaIII complexes were shown to be highly effective against a multidrug-resistant P. aeruginosa clinical isolate, with minimum inhibitory concentrations (MICs) of ≤1 μg/mL. Similarly, two of the InIII-based systems were particularly effective against the isolate, with an MIC of 8 μg/mL. These results show high promise in comparison with other, traditionally potent antibiotics, as the compounds generally indicated low cytotoxicity toward mammalian cells. Preliminary mechanistic investigations using pseudomonal transposon mutants suggested that the inhibitory effects of the InIII-based systems could be due to acute iron deficiency as a result of InIII-bound bacterioferritin.

The Effects of Inhibitor Chivosazole A on Actin Interacting with Profilin: A Theoretical Study

AbstractActin is highly conserved and contributes to numerous cellular activities. Profilin, one of actin binding proteins, promotes the exchange rate of nucleotide of actin, which leads to a fast elongation of actin filament. To slow down the elongation of filament, chivosazole A (ChivoA) is developed as an inhibitor of blocking actin‐profilin interaction. Intriguingly, known from the solved crystal structure, ChivoA does not bind on the interface between actin and profilin. Here, molecular dynamics (MD) simulation is used to study the possible mechanism how ChivoA inhibits actin‐profilin interaction. First, principal component analysis and representative structures comparisons reveal that the conformation of ChivoA‐bound actin is restrained at a closed state, whereas a trend toward an open state is found in profilin‐bound actin. Then, Peptide Gaussian accelerated MD shows that ChivoA limits the ability of the DNase I binding loop (D‐loop) swings and enlarges a distance between two major profilin binding regions. On the contrary, the distance between these two regions of profilin‐bound actin decreases in a clamp‐like motion mode. Finally, binding energies are calculated by molecular mechanics/poisson‐boltzmann surface area method and display that the ChivoA‐bound actin is less favorable for profilin binding.

A cobalt coordination complex binds on a unique binding site between domain-I and domain-III of serum albumin

Serum albumin binding influences physiological effects and pharmacokinetics of drugs. Major binding sites in serum albumin are sudlow sites I and II, located on domains IIA and IIIA, respectively. However, groove between domain I and III as a binding site is not well studied. In this work, we studied the binding of a cobalt coordination complex (DCoP) with bovine serum albumin (BSA) using multi-spectroscopic methods and molecular docking. DCoP strongly interacts with BSA with association constant of ∼7 × 105M−1. The binding was found to significantly alter protein's conformation and unfolding pathway. Results of this study shows that DCoP binds at the groove formed between domains III and I. We conclude that the groove is a rare binding site for large molecules and coordination complexes. The knowledge of unique binding site of serum albumin enlightens the comprehensive role of protein as a carrier biomacromolecule.

Cobaltabis(dicarbollide) Interaction with DNA Resolved at the Atomic Scale.

Boron neutron capture therapy represents a promising avenue for cancer treatment that requires nontoxic drugs with a high boron content efficiently distributed into cancerous cells. The metallacarborane o-cobaltabis(dicarbollide) ([COSAN]-) fulfills these requirements and constitutes an attractive candidate. Nevertheless, the interaction of this promising drug with nucleic acids, the assumed target of the biological damage, is poorly understood since contradictory results are reported in the literature. This work establishes the DNA/[COSAN]- interaction strength, mechanism, and time scale at the atomistic level by using a combination of microsecond-molecular dynamics and hybrid quantum mechanics/molecular mechanics simulations and by quantifying the absolute binding free energy. Results show that the DNA/[COSAN]- interaction is highly dependent on the ionic strength of the medium. A relatively weak DNA major groove binding (ΔGbind= -2.49 kcal/mol) driven mostly by dihydrogen B-H···H-N bonding is observed in the simulations only at a high NaCl concentration, whereas DNA intercalation mode is deemed highly unlikely.

Confocal image of three oxoaporphine alkaloids in cancer cell lines and their interaction with DNA by multispectroscopic and molecular docking techniques

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV–vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Unveiling the multifaceted interactions of antitumor drug mitoxantrone with ct-DNA through biophysical and in silico studies

Mitoxantrone, an anthraquinone derivative, is a widely used anticancer drug with its well-known ability to engage in complex interactions with DNA. Although known for its intercalating ability, the enigma surrounding its binding modes with DNA persists. The existing corpus of literature primarily focuses on mitoxantrone-DNA interactions with short DNA sequences, thereby yielding insights into its interactive nature is limited to this specific sequence. This study aims to elucidate the diverse modes with which mitoxantrone interacts with calf thymus DNA using a combination of spectroscopy, calorimetry and in silico studies. The findings from spectroscopic, calorimetric and molecular dynamic results in correlation with existing literature, unveil a fascinating narrative: mitoxantrone intercalates at lower concentrations but promotes condensation at higher concentrations. Although intercalation with side chains positioned in the minor/major groove is the major binding mode in GC-rich sequences, molecular modelling studies hint at an alternative binding mode in AT-rich sequences where it exclusively displays pure electrostatic interaction. These findings underscore the pivotal role of both drug structure and base sequence in dictating binding mode and affinity. Such insights not only deepen the understanding of structure-activity relationships but also hold promise for guiding future drug design strategies.

Metal-Based Drug-DNA Interactions and Analytical Determination Methods.

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA-metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

A second life for the crystallographic structure of Berenil-dodecanucleotide complex: a computational revisitation thirty years after its publication

AbstractThis study revisits the pioneering work of Professor Neidle, and co-workers, on the crystal structure of complexes formed between groove binders and DNA sequences. The original research revealed a DNA-ligand complex consisting of a dodecanucleotide bound with Berenil [1,3-bis(4′-amidinophenyl)-triazene] an anti-trypanocidal drug. This article aims to delve deeper into the structural dynamics of this system, showcasing the role played by water molecules in stabilizing the interaction between the ligand and the DNA. With this work, we reevaluate the findings from the original crystallographic study by employing modern molecular dynamics techniques, including Supervised Molecular Dynamics (SuMD) for generating binding trajectories, Thermal Titration Molecular Dynamics for assessing unbinding events, and AquaMMapS to identify regions occupied by stationary water molecules. The study addresses a minor and a major groove binding mode and assesses their strength and specificity using TTMD simulations, generating unbinding trajectories. This comprehensive approach integrates the understanding of the interaction of this DNA-ligand complex, which originated with the valuable work of Professor Neidle, resulting in an in-depth insight into the pivotal role of water molecules with this DNA, a behavior detected and extendable even to other nucleic acid complexes.

WITHDRAWN: Recent Advances in the Microbial Synthesis of Human Hemoglobin

Hemoglobin is a major binding protein in human red blood cells and plays an important role in the storage and transportation of oxygen. In recent years, the use of recombinant hemoglobin as a new type of oxygen carrier has attracted widespread attention. So far, the research on recombinant hemoglobin technology is in its early stages and there are still many problems, such as low yield and easy degradation. In this review, we summarize the molecular strategies for recombinant synthesis of human hemoglobin in microorganisms through metabolic engineering and synthetic biology techniques in recent years, and explore the possibility of preparing hemoglobin-based oxygen carriers based on fetal hemoglobin, in order to improve the yield of recombinant human hemoglobin and the sustained stability during protein production through protein engineering strategies, and to possibly reduce the toxic side effects of recombinant hemoglobin products.

Phytochemical analysis and pharmacological activities of essential oils extracted from Zingiber officinale (Roscoe) used in mediterranean diet: in vitro and in silico studies

ABSTRACT For their pungency and tanginess, ginger rhizomes (Zingiber officinale) are often used in cooking. Ginger has long been used in traditional medicine and home remedies to treat pain and inflammation. This research tests Z. officinale (EOZ) essential oils’ chemical composition, insecticidal, and antioxidant properties in vitro and in silico. EOZ yielded 0.69% of root mass with 23 chemicals. The main chemicals in EOZ were α-zingiberene (23.850%), Geranial (14.160%), and (E,E)-α-farnesene (9.980%). EOZ demonstrated noteworthy antioxidant activity in all tests, with an IC50 of 9.53 ± 0.41 mg/mL in the DPPH test and an EC50 of 87.46 ± 3.19 mg/mL in the FRAP system. The results indicate that EOZ has strong efficacy against C. maculatus, even at low concentrations (1.00 μL/100 g). Note that EOZ killed 20 ± 0% and 13.33 ± 4.44% of adult C. maculatus in inhalation and contact tests, respectively. High concentration (20.00 μL/100 g) resulted in 100% adult mortality in inhalation tests and 96.67 ± 4.44% mortality in contact testing. We then used molecular docking to identify EO major component binding modes by targeting insecticidal and antioxidant protein structures 1R20 and 1R4U. This research helps create insecticides and antioxidants from common ginger essential oil.

Myosin superfamily members during myelin formation and regeneration.

Myelin is an insulator that forms around axons that enhance the conduction velocity of nerve fibers. Oligodendrocytes dramatically change cell morphology to produce myelin throughout the central nervous system (CNS). Cytoskeletal alterations are critical for the morphogenesis of oligodendrocytes, and actin is involved in cell differentiation and myelin wrapping via polymerization and depolymerization, respectively. Various protein members of the myosin superfamily are known to be major binding partners of actin filaments and have been intensively researched because of their involvement in various cellular functions, including differentiation, cell movement, membrane trafficking, organelle transport, signal transduction, and morphogenesis. Some members of the myosin superfamily have been found to play important roles in the differentiation of oligodendrocytes and in CNS myelination. Interestingly, each member of the myosin superfamily expressed in oligodendrocyte lineage cells also shows specific spatial and temporal expression patterns and different distributions. In this review, we summarize previous findings related to the myosin superfamily and discuss how these molecules contribute to myelin formation and regeneration by oligodendrocytes.

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

BackgroundHepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PurposeTo investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. MethodsA mouse model of hepatic fibrosis was prepared with 20 % carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. ResultsIn vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. ConclusionGA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.

Complex Formation and Hydrolytic Processes of Protected Peptides Containing the -SXH- Motif in the Presence of Nickel(II) Ion.

Interactions between metal ions and proteins are considered reversible, such as the coordination of a metal ion to a protein or enzyme, but irreversible processes like the oxidative reactions, aggregation or hydrolytic processes may occur. In the presence of Ni(II)-ions selective hydrolysis of the peptides containing the -SXH- or -TXH- motif was observed. Since the side chain of histidine serves as the metal ion binding site for many native proteins, and very often histidine is present in a -SXH- or -TXH- sequence, to study the complex formation and hydrolytic processes in presence of nickel(II) ion four peptides were synthesised: Ac-SKHM-NH2, A3SSH-NH2, A4SSH-NH2, AAAϵKSH-NH2. The Ni(II)-induced hydrolysis of Ac-SKHM-NH2 peptide occurs rapidly in alkaline medium already at room temperature. In two peptides containing -SSH- sequence on the C-termini, the N-terminal part is the major binding site for the nickel(II) ion, but the formation of dinuclear complexes was also observed. In the [Ni2LH-6]2- complex of hexapeptide, the coordination sphere of the metal ions is saturated with deprotonated Ser-O-, which does not result in hydrolysis of the peptide. For A4SSH-NH2, both Ni(II) ions fulfill the conditions for hydrolysis, which was confirmed by HPLC analyses at pH ≈8.2 and 25 °C.

Development towards a novel screening method for nipecotic acid bioisosteres using molecular imprinted polymers (MIPs) as alternative to in vitro cellular uptake assays

Impaired expression of GABA transporters (GATs) is closely related to the pathogenesis of among others Parkinson's disease and epilepsy. As such, lipophilic nipecotic acid analogs have been extensively studied as GAT1-addressing drugs and radioligands but suffer from limited brain uptake due to the zwitterionic properties of the nipecotic acid moiety. Bioisosteric replacement of the carboxylic acid group is a promising strategy to improve the brain uptake, though it requires knowledge on the binding of these isosteres to GAT1. To screen nipecotic acid isosteres for their affinity to GAT1 in a time- and cost-effective manner, this research aims to develop a molecular imprinted polymer (MIP) that mimics the natural binding site of GAT1 and can act as an alternative screening tool to the current radiometric and mass spectrometry cellular-based assays. To this end, a nipecotic acid MIP was created using the electropolymerization of ortho-phenylenediamine (oPD) by cyclic voltammetry (CV). The optimization of the generated receptor layer was achieved by varying the scan rate (50–250 mV/s) and number of CV cycles (5–12), yielding an optimized MIP with an average imprinting factor of 2.6, a linear range of 1–1000 nm, and a theoretical LOD of 0.05 nm, as analyzed by electrical impedance spectroscopy (EIS). Selectivity studies facilitated the investigation of major binding interactions between the MIP and the substrate, building an experimental model that compares characteristics of various analogs. Results from this model indicate that the substrate carboxylic acid group plays a more important role in binding than an amine group, after comparing the binding of cyclohexanecarboxylic acid (average IF of 1.7) and piperidine (average IF of 0.46). The research culminates in a discussion regarding the feasibility of the in vitro model, comparing the synthetic system against the biological performance of GAT1. Thus, evaluating if it is possible to generate a synthetic GAT1 mimic, and if so, provide directions for follow-up research.

Lentiviral vector determinants of anion-exchange chromatography elution heterogeneity.

The demand for Lentiviral Vector (LV) drug substance is increasing. However, primary capture using convective anion-exchange chromatographyremains a significant manufacturing challenge. This stems from a poor understanding of the complex adsorption behaviors linked to LVs intricate and variable structure, such as high binding heterogeneity which is typically characterized by a gradient elution profile consisting of two peaks. Understanding which LV structural components drive these phenomena is therefore crucial for rational process design. This work identifies the key LV envelope components responsible for binding to quaternary-amine membrane adsorbents. Eliminating the pseudotype protein (Vesicular Stomatitis Virus G glycoprotein [VSV-G])did not impact the heterogenous two-peak elution profile, suggesting it is not a major binding species. Digestion of envelope glycosaminoglycans (GAGs), present on proteoglycans, leads to a dramatic reduction in the proportion of vector eluted in peak 2, decreasing from 50% to 3.1%, and a threefold increase in peak 1 maximum. Data from reinjection experiments point towards interparticle envelope heterogeneity from discrete LV populations, where the two-peak profile emerges from a subpopulation of LVs interacting via highly charged GAGs (peak 2) along with a weaker binding population likely interacting through the phospholipid membrane and envelope protein (peak 1).

Competitive Binding of Viral Nuclear Localization Signal Peptide and Inhibitor Ligands to Importin-α Nuclear Transport Protein.

Venezuelan equine encephalitis virus (VEEV) is a highly virulent pathogen whose nuclear localization signal (NLS) sequence from capsid protein binds to the host importin-α transport protein and blocks nuclear import. We studied the molecular mechanisms by which two small ligands, termed I1 and I2, interfere with the binding of VEEV's NLS peptide to importin-α protein. To this end, we performed all-atom replica exchange molecular dynamics simulations probing the competitive binding of the VEEV coreNLS peptide and I1 or I2 ligand to the importin-α major NLS binding site. As a reference, we used our previous simulations, which examined noncompetitive binding of the coreNLS peptide or the inhibitors to importin-α. We found that both inhibitors completely abrogate the native binding of the coreNLS peptide, forcing it to adopt a manifold of nonnative loosely bound poses within the importin-α major NLS binding site. Both inhibitors primarily destabilize the native coreNLS binding by masking its amino acids rather than competing with it for binding to importin-α. Because I2, in contrast to I1, binds off-site localizing on the edge of the major NLS binding site, it inhibits fewer coreNLS native binding interactions than I1. Structural analysis is supported by computations of the free energies of the coreNLS peptide binding to importin-α with or without competition from the inhibitors. Specifically, both inhibitors reduce the free energy gain from coreNLS binding, with I1 causing significantly larger loss than I2. To test our simulations, we performed AlphaScreen experiments measuring IC50 values for both inhibitors. Consistent with in silico results, the IC50 value for I1 was found to be lower than that for I2. We hypothesize that the inhibitory action of I1 and I2 ligands might be specific to the NLS from VEEV's capsid protein.

The 5'-terminal stem-loop RNA element of SARS-CoV-2 features highly dynamic structural elements that are sensitive to differences in cellular pH.

We present the nuclear magnetic resonance spectroscopy (NMR) solution structure of the 5'-terminal stem loop 5_SL1 (SL1) of the SARS-CoV-2 genome. SL1 contains two A-form helical elements and two regions with non-canonical structure, namely an apical pyrimidine-rich loop and an asymmetric internal loop with one and two nucleotides at the 5'- and 3'-terminal part of the sequence, respectively. The conformational ensemble representing the averaged solution structure of SL1 was validated using NMR residual dipolar coupling (RDC) and small-angle X-ray scattering (SAXS) data. We show that the internal loop is the major binding site for fragments of low molecular weight. This internal loop of SL1 can be stabilized by an A12-C28 interaction that promotes the transient formation of an A+•C base pair. As a consequence, the pKa of the internal loop adenosine A12 is shifted to 5.8, compared to a pKa of 3.63 of free adenosine. Furthermore, applying a recently developed pH-differential mutational profiling (PD-MaP) approach, we not only recapitulated our NMR findings of SL1 but also unveiled multiple sites potentially sensitive to pH across the 5'-UTR of SARS-CoV-2.

Co-occurrence of PRKN and SYNJ1 variants in Early-Onset Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM_004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM_003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD.

Moss biomass as effective biosorbents for heavy metals in contaminated water

The study explored batch adsorption of Cd(II) and Pb(II) ions using moss biomass from Barbula consanguinea and Hyophila involuta, assessing removal efficiency concerning various parameters. Both moss species showed high removal rates for Cd(II) (87 % for B. consanguinea and 89 % for H. involuta) and Pb(II) (93 % for B. consanguinea and 94 % for H. involuta) from contaminated water, reaching equilibrium within 30 min. While Cd(II) removal was pH-independent, Pb(II) removal showed pH-dependence, peaking at pH 5.0–5.5. Adsorption isotherm analysis indicated that the Langmuir, Freundlich, Elovich, Sips, and Redlich-Peterson models best described Cd(II) and Pb(II) adsorption onto both moss species (except for Cd(II) adsorption onto H. involuta), with R2 > 0.98. This confirms a heterogeneous surface with both monolayer and multilayer adsorption sites. The pseudo-second-order kinetic model confirmed chemisorption on moss biomass from both species. FTIR spectra identified major binding sites such as phenols, alkaloids, amines, alkenes, nitro compounds, and low-molecular-weight carbohydrates. EDS analysis validated the bonding of Cd(II) and Pb(II) ions to the biomass surface by displacing Ca(II) ions. According to the Langmuir model, moss biomass exhibited selective adsorption, favoring Pb(II) over Cd(II). B. consanguinea showed a higher adsorption capacity than H. involuta, which is attributed to its higher negative zeta potential. This study underscores the novelty of moss biomass for heavy metal removal in wastewater treatment, highlighting its sustainability, effectiveness, cost-efficiency, versatility, and eco-friendliness.