Binding Mechanism Research Articles

Identification of novel tau positron emission tomography tracers for chronic traumatic encephalopathy by comprehensive in silico screening and molecular dynamics simulation.

Chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive mild traumatic brain injury, is characterized neuropathologically by abnormal hyperphosphorylated tau accumulation. Early detection of tau deposition in the brain is crucial for the prevention and evaluation of CTE. Positron emission tomography (PET) tracers can image specific proteins, while the optimal PET tracer for CTE tau fibrils remains unidentified. In this study, structure-based virtual screening and CNS PET MPO algorithms were utilized to identify candidates for novel tau PET tracers from 23 000 compounds in the ChemDiv CNS BBB library. A total of 8 μs molecular dynamics simulations were then employed to evaluate their binding affinity and atomic-level interaction with CTE tau protofibrils. The results indicate that V017-7820 (CNS-4), S776-0061 (CNS-12), S567-0465 (CNS-18), and T828-0465 (CNS-25) exhibit higher docking scores and binding free energies with CTE tau protofibrils while also satisfying the fundamental physicochemical properties of PET tracers. Further simulation analyses reveal that CNS-4 has the strongest binding affinity to tau protofibrils among the four compounds. Hydrophobic, π-π stacking, and hydrogen bonding interactions are the primary driving forces for the binding of these compounds to CTE tau protofibrils. In particular, CNS-12 and CNS-25 exhibit more intense hydrophobic and π-π stacking interactions, whereas CNS-4 and CNS-25 exhibit stronger hydrogen bonding interactions. This study identifies promising lead compounds for tau PET tracers and highlights their mechanism of binding to CTE tau protofibrils, which provides new insights for further screening and development of novel PET tracers for CTE diagnosis.

Novel Schiff Base Sulfonate Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Docking Insights.

Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization of six novel Schiff base sulfonate derivatives (L1-L6) through spectroscopic techniques (FTIR and NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE), which are crucial therapeutic targets for diseases such as glaucoma, epilepsy, and Alzheimer's disease. The Kivalues for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of, 106.10 ± 14.73-422.80 ± 17.64 nM (THA: 159.61± 8.41 nM), 116.90 ± 24.40-268.00 ± 35.84 nM (AAZ: 439.17 ± 9.30 nM), and 177.00 ± 35.03-435.20 ± 75.98 nM (AAZ: 98.28 ± 1.69 nM), respectively. Molecular docking analyses revealed key interactions within the active sites of the enzymes, including hydrogen bonding with critical residues and π-π stacking interactions. Notably,L3demonstrated superior inhibition against hCA I (Ki: 116.90 ± 24.40 nM) and AChE (Ki: 106.10 ± 14.73 nM), positioning it as a promising lead compound. This comprehensive investigation contributes to the development of isoform-specific inhibitors for therapeutic use and provides valuable insights into their binding mechanisms.

BIOACTIVE COMPOUNDS OF Moringa oleifera AS KRASG12C INHIBITORS IN COLORECTAL CANCER: IN SILICO STUDY

KRAS is a GTPase enzyme that regulates cell growth and division. Mutations in KRAS can lead to its permanent activation, resulting in uncontrolled cell growth and cancer progression. Approximately 30–44% of colorectal cancer cases harbor KRAS mutations, with 1–3% involving the KRASG12C variant. Historically considered "undruggable," recent advancements, such as Sotorasib, have demonstrated the potential to target KRASG12C effectively, making it a promising focus for drug discovery. Moringa oleifera, a plant rich in phytochemicals, is a potential source of bioactive compounds with therapeutic applications. In this study, 218 compounds derived from M. oleifera were screened using molecular docking, targeting KRASG12C. Quercetin (3) exhibited the lowest binding affinity (-9.37 kcal/mol) and showed interactions with key residues, including GLN100A, VAL104A, LYS17A, and TYR97A, suggesting a binding mechanism similar to that of Sotorasib as native ligand. The physicochemical analysis further revealed high gastrointestinal absorption, good lipophilicity, and favorable bioavailability scores for Quercetin (3), supporting its potential as a drug candidate. These findings highlight the potential of M. oleifera compounds, particularly quercetin (3), as inhibitors of KRASG12C in colorectal cancer.

Separation and Dynamic Binding Mechanism of 3D Model Animation by Integrating Improved Genetic Algorithm and WebAR

With the development of the economy, the demand for 3D model animation in fields such as games, film and television, and education is constantly increasing. At present, many 3D model animations are built based on genetic algorithm. However, due to the slow convergence speed and poor local search ability of genetic algorithm, this model still has many shortcomings. Therefore, a cellular automaton is used to optimize the genetic algorithm, and a cellular genetic algorithm is proposed. It is integrated with WebAR technology, which has the characteristics of lightweight and low cost, aiming to improve the separation and dynamic binding mechanism of 3D model animation. Experimental analysis showed that when the number of chromosome genes was 90, the vertex gene value of the research algorithm was the highest, ranging from 281 to 501, and the convergence was the highest. The file size of the model dataset based on the research method was reduced by 50% compared with before. The FPDT based on the animation separation and dynamic binding mechanism was decreased by 15.2 s on average. To sum up, it can be seen that the designed 3D model animation is more detailed and the animation dynamic is also the best. This research method can significantly improve the separation and dynamic binding mechanism of 3D model animation. This research will improve the integration of genetic algorithm and WebAR technology, which can not only effectively deal with complex 3D models and animations, but also has broad application prospects.

Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties

Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH’s unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent.

Understanding the binding mechanisms of hydroxy-chalcone-based 24-membered macrocyclic bis-epoxide with beta-lactoglobulin

The lipocalin carrier protein, β-lactoglobulin (β-lg), stands out as a crucial protein in the food industry, known for its ability to effectively bind with hydrophobic small molecules. However, it was unclear how β-lg interacts with macrocyclic molecules. In this research, we focused on two key aspects. First, we synthesized a 24-membered macrocycle 4d by modifying a natural product chalcone to create a macrocycle by connecting two ortho-hydroxyl groups of each phenyl ring of two chalcone units with alkyl chains. To enhance solubility, we converted the chalcone CC bonds to epoxide rings. Second, we investigated the binding ability and mechanism of binding of the compound with the β-lg. The β-lg and 4d interaction shows an isoemissive point at 382 nm with Kb = 4.64 ± 0.02 × 105 at 298 K, indicating the excellent protein binding ability of 4d. Remarkably, despite its size, 4d binds to the protein without altering its conformation, suggesting the availability of a spacious binding site on the protein where the molecule fits well. Molecular docking analysis confirmed the presence of such a site at the mouth of the calyx. Additionally, our 200 ns molecular dynamics simulation demonstrated that 4d adopts a conformation to interact with the hydrophobic amino acids of the binding site, ultimately stabilizing the protein.

Innovative dual-benefit recycling and sustainable management of municipal solid waste incineration fly ash via ultra-high performance concrete

Millions of tons of municipal solid waste incineration fly ash are generated worldwide each year. Currently, landfilling is the primary disposal method, consuming vast land resources and posing significant risks of soil and groundwater contamination due to the high concentration of hazardous heavy metals. Thus, this study investigated the potential of recycling hazardous municipal solid waste incineration fly ash into non-hazardous ultra-high performance concrete for sustainable development. The mechanisms of heavy metal solidification and binding were examined through Density Functional Theory calculations and microscale experiments. Heavy metals are solidified through the adsorption and binding effects of calcium silicate hydrate and the encapsulation effect of the compact accumulation within the concrete structure. The pore structure of the concrete and the chemical reactions between the fly ash and cement were analyzed to validate the heavy metal solidification mechanism. After solidification, the leaching concentrations of heavy metals from the concrete were two orders of magnitude lower than the limit specified by the Toxicity Characteristic Leaching Procedure. The autogenous shrinking of UHPC with MSWIFA was reduced by about 50 %, and the compressive strength of the concrete decreased. The incorporation of MSWIFA led to approximately a 20 % reduction in energy consumption and carbon emissions. The concrete with MSWIFA exhibited better overall performance. This study presents an innovative and effective approach for recycling municipal solid waste incineration fly ash into non-hazardous concrete, contributing to sustainable hazardous waste management and reducing environmental pollution caused by heavy metals.

Targeted Regulation of Osteoblasts and Osteoclasts in Osteosarcoma Patients by CSF3R Receptor Inhibition of Osteolysis Caused by Tumor Inflammation Based on Transcriptional Spectrum Analysis and Drug Library Screening.

Osteosarcoma (OS) is a common primary malignant bone tumor that mainly occurs in children and adolescents. The use of IL-8 inhibitor compounds has been reported in patents, which can be used to treat and/or prevent osteosarcoma, but the pathogenesis of osteosarcoma remains to be investigated. At present, osteoblasts and osteoclasts play an important role in the occurrence and development of OS. However, the relationship between osteoblasts and osteoclasts in the specific participation mechanism and inflammatory response of OS patients has not been further studied. The transcriptome, clinical data, and other data related to OS were downloaded from the GEO database to analyze them with 200 known inflammatory response genes. We set the screening conditions as p < 0.05 and | log2FC| > 0.50, screened the differentially expressed genes (DEGs) related to OS, tested the correlation coefficient between the OS INF gene and clinical risk, and analyzed the survival prognosis. We further enriched and analyzed the DEGs and inflammatory response genes of OS with GO/KEGG to explore the potential biological function and signal pathway mechanism of OS inflammatory response genes. Moreover, the virtual screening of drug sensitivity of OS based on the FDA drug library was also carried out to explore potential therapeutic drugs targeted to regulate OS osteogenesis and osteoclast inflammation, and finally, the molecular dynamics simulation verification of OS core protein and potential drugs was carried out to explore the binding stability and mechanism between potential drugs and core protein. Through differential analysis of GSE39058, GSE36001, GSE87624, and three other data sets closely related to OS osteoblasts and osteoclasts, we found that there was one upregulated gene (CADM1) and one down-regulated gene (PHF15) related to OS. In addition, GSEA enrichment analysis of the DEGs of OS showed that it was mainly involved in the progress of OS through biological functions, such as oxidative photosynthesis, acute junction, and epithelial-mesenchymal transition. The enrichment analysis of OS DEGs revealed that they mainly affect the occurrence and progress of OS by participating in the regulation of the actin skeleton, PI3K Akt signal pathway, complement and coagulation cascade. According to the expression of CSF3R in OS patients, a risk coefficient model and a diagnostic model were established. It was found that the more significant the difference in the CSF3R gene in OS patients, the greater the risk coefficient of disease (p < 0.05). The AUC under the curve of the CSF3R gene was greater than 0.65, which had a good diagnostic significance for OS. The above results showed that the prognosis risk gene CSF3R related to OS inflammation was closely related to the survival status of OS patients. Finally, through the virtual screening of the ZINC drug library and molecular dynamics simulation, it was found that the docking model formed by the core protein CSF3R and the compounds, Leucovorin and Methotrexate, were the most stable, which revealed that the compounds Leucovorin and Methotrexate might play a role in the treatment of OS by combining with the inflammatory response related factor CSF3R of OS. CSF3R participates in the occurrence and development of OS bone destruction by regulating the inflammatory response of osteoblasts and osteoclasts and can affect the survival prognosis of OS patients.

Design, In silico Screening, Synthesis, Characterisation and DFT-based Electronic Properties of Dihydropyridine-based Molecule as L-type Calcium Channel Blocker.

People of all nationalities and social classes are now affected by the growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A range of therapeutic compounds, on the other hand, are often used to handle hypertension. The objectives of this study are first to design potential antihypertensive drugs based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise the best ligand. Due to the lack of 3D structures for human Cav1.2, the protein structure was modelled using a homology modelling approach. A protein-ligand complex's strength and binding interaction were investigated using molecular docking and molecular dynamics techniques. DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2- TZVP level of theory. The SwissADME website was used to study the ADMET properties. In this study, a series of DHP compounds (19 compounds) were properly designed to act as calcium channel blockers. Among these compounds, compound 16 showed excellent binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised. To assess the structural features of the synthesised molecule quantum chemical calculations were performed. Based on molecular docking, molecular dynamics simulations, and drug-likeness properties of compound 16 can be used as a potential calcium channel blocker.

Order/Disorder Transitions Upon Protein Binding: A Unifying Perspective.

When two proteins bind to each other, this process is often accompanied by a change in their structural states (from disordered to ordered or vice versa). As it turns out, there are 10 distinct possibilities for such binding-related order/disorder transitions. Out of this number, seven scenarios have been experimentally observed, while another three remain hitherto unreported. As an example, we discuss the so-called mutual synergistic folding, whereby two disordered proteins come together to form a fully structured complex. Our bioinformatics analysis of the Protein Databank found potential new examples of this remarkable binding mechanism.

Unifying Theory and Experiments: Multi-Target Pharmacology of Dajihan Pill Against Hyperlipidemia

Background: The increasing incidence of hyperlipidemia (HLP) is attributed to the imbalance in redox homeostasis, aberrant lipid metabolism, and the excessive intake of empty calories. Dajihan Pill (DJHP) is a Traditional Chinese Medicine (TCM) formula composed of Zingiberis Rhizoma (ZR), Piperis Longi Fructus (PLF), Alpiniae Officinarum Rhizome (AOR), and Cinnamomi Cortex (CC) in a ratio of 3:2:3:2. It exhibits a significant preventive effect on HLP. Certainly, the active components and the precise mechanism of action are not fully understood. Therefore, this study aims to elucidate the preventive and ameliorative mechanisms of DJHP against HLP by integrating network pharmacology, molecular docking, and experimental validation. Methods: Based on the pharmacological method, active ingredients in DJHP and targets were extracted from Traditional Chinese Medicine System Pharmacology (TCMSP) and UniProt. Then core compounds and targets were obtained by constructing “compounds-targets-disease” and proteinprotein interaction (PPI) network. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to elucidate further the associated action mechanism. The molecular binding mechanisms between the core ingredients and targets were elucidated through molecular docking. Additionally, the antioxidant capacities of DJHP extracts were investigated by assessing their DPPH, hydroxyl, and ABTS radical scavenging activities. Results: A total of 45 active compounds and 258 targets were identified in DJHP. Network analysis indicated that quercetin, beta-sitosterol, kaempferol, and oleic acid might serve as core bioactive compounds. Seven core targets, including AKT1, INS, and TNF, were identified as potential preventive targets. GO analysis suggested the improvement of HLP by DJHP may be related to the lipid metabolic process, high-density lipoprotein particle, triglyceride binding, and inflammatory response. The KEGG analysis indicated TNF, HIF-1, and AMPK signaling pathways were involved. The observations of active compounds binding with core targets indicated an excellent combination. Additionally, antioxidant results showed that DJHP exhibited significant DPPH, hydroxyl, and ABTS radical scavenging activities. Conclusion: Theoretical and experimental investigations indicate that DJHP can effectively modulate various signaling pathways and enhance the redox system, thus mitigating HLP. Our work provided a basis for the pharmacological study of DJHP in preventing HLP and further research.

A highly selective colorimetric chemosensor based on Salicylaldehyde Schiff base for Cu+2 and F− ions detection with a turn-off response for copper (II) ion: Experimental and theoretical studies

A salicylaldehyde-Schiff base ligand (SS) containing a pyridine-2-carboxamidine group was synthesized via a simple and convenient method to facilitate the highly selective colorimetric detection of Cu+2 and F− ions. Employing colorimetric, UV–visible, and fluorescence techniques, as well as 1H NMR titration experiments, we assessed the sensing capabilities of the synthesized sensor SS towards Cu+2 and F− ions. The developed sensor showed remarkable selectivity in the presence of competing ions, with a color transition from colorless to yellow and orange in the presence of Cu+2 and F− ions respectively. The detection limits for Cu+2 and F− ions were determined to be 1.7×10−5 M and 1.94×10−4 M, respectively, using UV-visible analysis. Notably, the fluorescence experiment displayed a significantly lower detection limit for Cu+2 ion, approximately 6.6 μM. Analysis of the spectroscopic data using Job's plot revealed a 1:2 binding stoichiometry between Cu+2 and SS, while 1:1 complex formation was observed between SS and F− ions. Density functional theory (DFT) calculations enabled us to explore the optimized structures, electronic properties, and binding mechanisms of the SS, SS-F− adduct, and SS-Cu+2 complexes. These computations revealed a reduction in the HOMO-LUMO energy gap for SS upon its interaction with fluoride and copper species, consistent with the experimental observations.

Identification of Coumarin-Chalcone and Coumarin-Pyrazoline Derivatives as Novel Anti-Toxoplasma gondii Agents.

Toxoplasmosis, a zoonotic infection caused by the apicomplexan parasite Toxoplasma gondii, affects a significant portion of the global human population. This condition, particularly dangerous for pregnant women and immunocompromised individuals, currently lacks effective treatment options. Eighteen coumarin-based derivatives were synthesized, comprising coumarin-chalcone hybrids (5a-i) and coumarin-pyrazoline hybrids (6a-i). Cytotoxicity was evaluated using L929 mouse fibroblasts and Hs27human fibroblasts. Anti-T. gondii activity was assessed, and molecular docking studies were performed to predict binding modes with TgCDPK1. Pyrazoline hybrids (6a-i) showed lower toxicity than chalcone-bearing coumarins (5a-i), with CC30 values exceeding the highest tested concentration (500µg/mL) for most compounds. The synthesized molecules demonstrated strong anti-T. gondii activity, with IC50 values ranging from 0.66µg/mL to 9.05µg/mL. Molecular docking studies provided insights into potential binding mechanisms. This study highlights the potential of coumarin-based hybrids as anti-T. gondii agents. The findings should contribute to the growing arsenal of small molecules against T. gondii and underscore the value of molecular hybridization in drug design. Further studies to elucidate these compounds' mechanism of action and in vivo efficacy are warranted to fully realize their potential as anti-parasitic agents.

Deciphering non-covalent binding mechanism of olive biophenolic secoiridoids interaction with β-lactoglobulin: Multi-spectroscopies, thermodynamics, molecular docking, and molecular dynamics simulation

The non-covalent binding mechanism between β-lactoglobulin (β-LG) and four typical olive biophenolic secoiridoids, including oleuropein (OLE), hydroxytyrosol (HT), oleacein (OLEA), and oleocanthal (OLEO) was delineated using a combination of multi-spectroscopies, thermodynamics, molecular docking, and molecular dynamics simulations. The fluorescence quenching results indicated all the secoiridoids were able to form a stable complexation with β-LG. Among them, OLEA with a high binding constant 122.46 × 102 L mol−1 at 293 K, had a stronger binding ability to β-LG in a static quenching effect than OLE or HT with binding constant 11.53 or 21.13 × 102 L mol−1 in a dynamic quenching effect. The binding processes of all the secoiroids with β-LG were spontaneous, as indicated by negative ΔG values. The binding to β-LG by OLEA or OLEO mainly resulted from intermolecular hydrophobic forces, showing that their ΔH values reached 78.58 or 32.34 kJ mol−1; whereas the binding to β-LG by OLE and HT was mainly involved in hydrogen bonds, showing that their values of ΔH reached 12.72 and 14.92 kJ mol−1, respectively. The results from circular dichroism spectra indicated the secondary structure of β-LG was induced by OLE, HT and OLEO with a decrease in α-helix and an increase level in β-sheet. On the contrary, the increased level of α-helix and β-turn and decreased β-sheet for β-LG were induced by OLEA, which was corroborated by Raman spectra's observations. The β-LG exhibited a preference for binding to the compound with a lower molecular weight (MW) such as HT, OLEA or OLEO, primarily within the hydrophobic interior, facilitated by hydrophobic interactions and hydrogen bonding. However, OLE, with a higher MW, was more likely to bind to the exterior surface of β-LG through hydrogen bonding. Furthermore, the results of structure-affinity relationship indicated the gap energy ΔE(LUMO-HOMO) of OLEA and OLEO was strongly responsible for binding to β-LG. These findings will provide an insightful perception for formulating functional milk beverages incorporating olive biophenolic secoiridoids.

Experimental study on crack repair materials for masonry ancient building based on skeleton effect

In order to obtain “repair the old as the old” ancient building crack repair materials and cracks on both sides of the wall does not produce internal stress and secondary damage, this study uses acrylamide as the core gelling material, brick powder as the force transmitting skeleton of the hydrogel material modification, the preparation of the brick powder hydrogel. The dry density, modulus of elasticity, compressive strength, toughness and dissolution properties of hydrogels with different grey brick powder admixtures were tested. Scanning electron microscopy (SEM) was used to reveal the binding mechanism in the microstructure of acrylamide hydrogel modified with brick powder. The results show that the grey brick powder particles can be embedded in the three-dimensional network structure of the hydrogel in a more complete way, which effectively improves the mechanical properties and swelling properties of the hydrogel itself; With the increase in the proportion of brick powder, the dry density, compressive strength, toughness of the brick powder hydrogel were significantly increased, and the equilibrium swelling was significantly reduced, when the proportion of 70 % of compressive strength increased by 2998.06 %, toughness increased by 2250.03 %, and the equilibrium swelling was reduced by 716.12 %. Brick powder hydrogel performance and color meet the requirements of crack repair in masonry ancient building.

Exclusion of Superinfection or Enhancement of Superinfection in Pestiviruses—APPV Infection Is Not Dependent on ADAM17

Some viruses can suppress superinfections of their host cells by related or different virus species. The phenomenon of superinfection exclusion can be caused by inhibiting virus attachment, receptor binding and entry, by replication interference, or competition for host cell resources. Blocking attachment and entry not only prevents unproductive double infections but also stops newly produced virions from re-entering the cell post-exocytosis. In this study, we investigated the exclusion of superinfections between the different pestivirus species. Bovine and porcine cells pre-infected with non-cytopathogenic pestivirus strains were evaluated for susceptibility to subsequent superinfection using comparative titrations. Our findings revealed significant variation in exclusion potency depending on the pre- and superinfecting virus species, as well as the host cell species. Despite this variability, all tested classical pestivirus species reduced host cell susceptibility to subsequent infections, indicating a conserved entry mechanism. Unexpectedly, pre-infection with atypical porcine pestivirus (APPV) increased host cell susceptibility to classical pestiviruses. Further analysis showed that APPV can infect SK-6 cells independently of ADAM17, a critical attachment factor for the classical pestiviruses. These results indicate that APPV uses different binding and entry mechanisms than the other pestiviruses. The observed increase in the susceptibility of cells post-APPV infection warrants further investigation and could have practical implications, such as aiding challenging pestivirus isolation from diagnostic samples.

Novel Easy‐to‐Synthesize Hydrazine Multi‐channel Detection and Adsorption Materials

Comprehensive SummaryHydrazine hydrate (DH) is a widely used chemical agent, but it is highly toxic. Thus, the development of low‐cost and easy‐to‐prepare materials for the detection and adsorption of DH is very significant. Herein, a novel and easy‐to‐prepare supramolecular smart material based on bisquinoline‐functionalized naphthalene diimide (DQ8) has been designed and synthesized. In the DQ8, the synergistic effect between quinoline and naphthalene diimide groups has been employed to improve the selectivity and sensitivity for binding of DH. The DQ8‐based crystalline porous material (DQ8‐CPM) can simultaneously detect and adsorb DH and produce noticeable fluorescence color changes after adsorption of DH vapor. More significantly, the DQ8‐CPM shows nice recycling performance on DH detection and adsorption. Meanwhile, a smart gel based on DQ8 (DQ8‐G) shows multi‐channel response for DH through color, fluorescence, and state changes. The DQ8 shows high selectivity and sensitivity for DH. The detection limit of DQ8 for DH is 8.6 × 10–7 mol/L. According to the investigation of the DH binding and response mechanism, the synergistic effect between quinoline and naphthalene diimide groups plays an important role in the DH response process. It's a simple and feasible way to develop materials for detection and adsorption of DH through synergistic effects.

Saccharibacteria deploy two distinct Type IV pili, driving episymbiosis, host competition, and twitching motility.

All cultivated Patescibacteria, or CPR, exist as obligate episymbionts on other microbes. Despite being ubiquitous in mammals and environmentally, molecular mechanisms of host identification and binding amongst ultrasmall bacterial episymbionts are largely unknown. Type 4 pili (T4P) are well conserved in this group and predicted to facilitate symbiotic interactions. To test this, we targeted T4P pilin genes in Saccharibacteria Nanosynbacter lyticus strain TM7x to assess their essentiality and roles in symbiosis. Our results revealed that N. lyticus assembles two distinct T4P, a non-essential thin pili that has the smallest diameter of any T4P and contributes to host-binding, episymbiont growth, and competitive fitness relative to other Saccharibacteria, and an essential thick pili whose functions include twitching motility. Identification of lectin-like minor pilins and modification of host cell walls suggest glycan binding mechanisms. Collectively our findings demonstrate that Saccharibacteria encode unique extracellular pili that are vital mediators of their underexplored episymbiotic lifestyle.

A multiscale in silico approach to impede the interaction between Dengue NS1 and Human RPL18, aiming to suppress the Dengue viral translation and proliferation

A multiscale <i>in silico</i> approach to impede the interaction between Dengue NS1 and Human RPL18, aiming to suppress the Dengue viral translation and proliferation

Electrochemical probing of encapsulation process for polymeric micelles

Many of the drugs used in pharmaceutical formulations are not photoactive. Cyclic voltammetry and differential pulse voltammetry can unveil hidden information about the binding mechanism between the host and guest. This work aims to demonstrate that electrochemical techniques can be used to monitor the binding mechanism. The electrochemical reversibility, stability, and the effect of time were investigated. Also, the kinetics parameter, binding constant, and apparent diffusion coefficient were estimated. The reversibility and stability increased when toluidine blue was in the surfactant medium. The effect of time showed that the toluidine blue did not permeate the copolymeric micelles. Although F-127 copolymer is more hydrophilic, the toluidine blue, bonded more effectively in P-123 (Kb = 3,846 L/mol) than in F-127 (Kb = 184 L/mol). The kinetics parameter corroborated with the Kb. The Dapp found in P-123 and F-127 micelles followed an unexpected trend, 3.7 and 4.8 μcm2 s−1, respectively.