High-Performance, High-Resolution Quantum Dot Light-Emitting Diodes with Self-Assembly Single-Molecular Interface Modification.

With the development of near-eye displays, the demands for display resolution and performance are increasing. Quantum dot performance is virtually independent of pixel size, making it an efficient way to display ultrahigh resolution. However, the low efficiency of high-resolution quantum dot devices has been an urgent technical bottleneck to be solved. Here, we constructed a dense single-molecule modification layer and a leakage current blocking layer for high-resolution devices using self-assembly, thereby realizing ultrahigh-resolution, high-efficiency, and stable high-resolution quantum dot light-emitting diodes (QLEDs). The peak external quantum efficiencies of the red devices are 24.68% (8759 PPI) and 19.54% (26075 PPI), respectively, with an exceptional long lifetime (T95@1000 nit) up to 4871 h. In addition, we explored the feasibility of this modification strategy on non-Cd-based quantum dots. In conclusion, our strategy effectively improves the performance of high-resolution devices and provides a superior approach for realizing near-eye display applications.

Molecular modification and biotechnological applications of microbial aspartic proteases.

The growing preference for incorporating microbial aspartic proteases in industries is due to their high catalytic function and high degree of substrate selectivity. These properties, however, are attributable to molecular alterations in their structure and a variety of other characteristics. Molecular tools, functional genomics, and genome editing technologies coupled with other biotechnological approaches have aided in improving the potential of industrially important microbial proteases by addressing some of their major limitations, such as: low catalytic efficiency, low conversion rates, low thermostability, and less enzyme yield. However, the native folding within their full domain is dependent on a surrounding structure which challenges their functionality in substrate conversion, mainly due to their mutual interactions in the context of complex systems. Hence, manipulating their structure and controlling their expression systems could potentially produce enzymes with high selectivity and catalytic functions. The proteins produced by microbial aspartic proteases are industrially capable and far-reaching in regulating certain harmful distinctive industrial processes and the benefits of being eco-friendly. This review provides: an update on current trends and gaps in microbial protease biotechnology, exploring the relevant recombinant strategies and molecular technologies widely used in expression platforms for engineering microbial aspartic proteases, as well as their potential industrial and biotechnological applications.

D-allulose 3-epimerase for low-calorie D-allulose synthesis: microbial production, characterization, and applications.

D-allulose, an epimer of D-fructose at C-3 position, is a low-calorie rare sugar with favorable physiochemical properties and special physiological functions, which displays promising perspectives in the food and pharmaceutical industries. Currently, D-allulose is extremely sparse in nature and is predominantly biosynthesized through the isomerization of D-fructose by D-allulose 3-epimerase (DAEase). In recent years, D-allulose 3-epimerase as the key biocatalyst for D-allulose production has received increasing interest. The current review begins by providing a summary of D-allulose regarding its characteristics and applications, as well as different synthesis pathways dominated by biotransformation. Then, the research advances of D-allulose 3-epimerase are systematically reviewed, focusing on heterologous expression and biochemical characterization, crystal structure and molecular modification, and application in D-allulose production. Concerning the constraint of low yield of DAEase for industrial application, this review addresses the various attempts made to promote the production of DAEase in different expression systems. Also, various strategies have been adopted to improve its thermotolerance and catalytic activity, which is mainly based on the structure-function relationship of DAEase. The application of DAEase in D-allulose biosynthesis from D-fructose or low-cost feedstocks through single- or multi-enzymatic cascade reaction has been discussed. Finally, the prospects for related research of D-allulose 3-epimerase are also proposed, facilitating the industrialization of DAEase and more efficient and economical bioproduction of D-allulose.

Machine Learning Exploration of the Relationship Between Drugs and the Blood-Brain Barrier: Guiding Molecular Modification.

OBJECTIVE: This study aimed to improve the efficiency of pharmacotherapy for CNS diseases by optimizing the ability of drug molecules to penetrate the Blood-Brain Barrier (BBB). METHODS: We established qualitative and quantitative databases of the ADME properties of drugs and derived characteristic features of compounds with efficient BBB penetration. Using these insights, we developed four machine learning models to predict a drug's BBB permeability by assessing ADME properties and molecular topology. We then validated the models using the B3DB database. For acyclovir and ceftriaxone, we modified the Hydrogen Bond Donors and Acceptors, and evaluated the BBB permeability using the predictive model. RESULTS: The machine learning models performed well in predicting BBB permeability on both internal and external validation sets. Reducing the number of Hydrogen Bond Donors and Acceptors generally improves BBB permeability. Modification only enhanced BBB penetration in the case of acyclovir and not ceftriaxone. CONCLUSIONS: The machine learning models developed can accurately predict BBB permeability, and many drug molecules are likely to have increased BBB penetration if the number of Hydrogen Bond Donors and Acceptors are reduced. These findings suggest that molecular modifications can enhance the efficacy of CNS drugs and provide practical strategies for drug design and development. This is particularly relevant for improving drug penetration of the BBB.

The molecular modification, expression, and the antibacterial effects studies of human lysozyme.

Human lysozyme (hLYZ) has attracted considerable research attention due to its natural and efficient antibacterial abilities and widespread uses. In this study, hLYZ was modified to enhance its enzyme activity and expressed in a Pichia pastoris expression system. A combination mutant HZM(2R-K)-N88D/V110S demonstrated the highest enzyme activity (6213 ± 164 U/mL) in shake flasks, which was 4.07-fold higher when compared with the original strain. Moreover, the recombinant P. pastoris was inducted in a 3 L bioreactor plus methanol/sorbitol co-feeding. After 120 h induction, the antibacterial activity of hLYZ reached 2.23 ± 0.12 × 105 U/mL, with the specific activity increasing to 1.89 × 105 U/mg, which is currently the highest specific activity obtained through recombinant expression of hLYZ. Also, hLYZ supernatants showed 2-fold inhibitory effects toward Staphylococcus aureus and Micrococcus lysodeikticus when compared with HZM(2R-K). Our research generated a hLYZ mutant with high antibacterial capabilities and provided a method for screening of high-quality enzymes.

Advancements in the Heterologous Expression of Sucrose Phosphorylase and Its Molecular Modification for the Synthesis of Glycosylated Products.

Sucrose phosphorylase (SPase), a member of the glycoside hydrolase GH13 family, possesses the ability to catalyze the hydrolysis of sucrose to generate α-glucose-1-phosphate and can also glycosylate diverse substrates, showcasing a wide substrate specificity. This enzyme has found extensive utility in the fields of food, medicine, and cosmetics, and has garnered significant attention as a focal point of research in transglycosylation enzymes. Nevertheless, SPase encounters numerous obstacles in industrial settings, including low enzyme yield, inadequate thermal stability, mixed regioselectivity, and limited transglycosylation activity. In-depth exploration of efficient expression strategies and molecular modifications based on the crystal structure and functional information of SPase is now a critical research priority. This paper systematically reviews the source microorganisms, crystal structure, and catalytic mechanism of SPase, summarizes diverse heterologous expression systems based on expression hosts and vectors, and examines the application and molecular modification progress of SPase in synthesizing typical glycosylated products. Additionally, it anticipates the broad application prospects of SPase in industrial production and related research fields, laying the groundwork for its engineering modification and industrial application.

Research and application progress of microbial ß-mannanases: a mini-review.

Mannan is a predominant constituent of cork hemicellulose and is widely distributed in various plant tissues. ß-Mannanase is the principal mannan-degrading enzyme, which breaks down the ß-1,4-linked mannosidic bonds in mannans in an endo-acting manner. Microorganisms are a valuable source of ß-mannanase, which exhibits catalytic activity in a wide range of pH and temperature, making it highly versatile and applicable in pharmaceuticals, feed, paper pulping, biorefinery, and other industries. Here, the origin, classification, enzymatic properties, molecular modification, immobilization, and practical applications of microbial ß-mannanases are reviewed, the future research directions for microbial ß-mannanases are also outlined.

Thermophilic ß-mannanases from bacteria: production, resources, structural features and bioengineering strategies.

ß-mannanases are pivotal enzymes that cleave the mannan backbone to release short chain mannooligosaccharides, which have tremendous biotechnological applications including food/feed, prebiotics and biofuel production. Due to the high temperature conditions in many industrial applications, thermophilic mannanases seem to have great potential to overcome the thermal impediments. Thus, structural analysis of thermostable ß-mannanases is extremely important, as it could open up new avenues for genetic engineering, and protein engineering of these enzymes with enhanced properties and catalytic efficiencies. Under this scope, the present review provides a state-of-the-art discussion on the thermophilic ß-mannanases from bacterial origin, their production, engineering and structural characterization. It covers broad insights into various molecular biology techniques such as gene mutagenesis, heterologous gene expression, and protein engineering, that are employed to improve the catalytic efficiency and thermostability of bacterial mannanases for potential industrial applications. Further, the bottlenecks associated with mannanase production and process optimization are also discussed. Finally, future research related to bioengineering of mannanases with novel protein expression systems for commercial applications are also elaborated.

Adsorbed p-Aminothiophenol Molecules on Platinum Nanoparticles Improve Electrocatalytic Hydrogen Evolution.

Electrocatalytic hydrogen evolution is an important approach to produce clean energy, and many electrocatalysts (e.g., platinum) are developed for hydrogen production. However, the electrocatalytic efficiency of commonly used metal catalysts needs to be improved to compensate their high cost. Herein, the electrocatalytic efficiency of platinum nanoparticles (PtNPs) in hydrogen evolution is largely improved via simple surface adsorption of sub-monolayer p-aminothiophenol (PATP) molecules. The overpotential goes down to 86.1 mV, which is 50.2 mV lower than that on naked PtNPs. This catalytic activity is even better than that of 20 wt.% Pt/C, despite the much smaller active surface area of PATP-adsorbed PtNPs than Pt/C. It is theoretically and experimentally confirmed that the improved electrocatalytic activity in hydrogen evolution can be attributed to the change in electronic structure of PtNPs induced by surface adsorption of PATP molecules. More importantly, this strategy can also be used to improve the electrocatalytic activity of palladium, gold, and silver nanoparticles. Therefore, this work provides a simple, convenient, and versatile method for improving the electrocatalytic activity of metal nanocatalysts. This surface adsorption strategy may also be used for improving the efficiency of many other nanocatalysts in many reactions.

Expression and Molecular Modification of Chitin Deacetylase from Streptomyces bacillaris.

Chitin deacetylase can be used in the green and efficient preparation of chitosan from chitin. Herein, a novel chitin deacetylase SbCDA from Streptomyces bacillaris was heterologously expressed and comprehensively characterized. SbDNA exhibits its highest deacetylation activity at 35 °C and pH 8.0. The enzyme activity is enhanced by Mn2+ and prominently inhibited by Zn2+, SDS, and EDTA. SbCDA showed better deacetylation activity on colloidal chitin, (GlcNAc)5, and (GlcNAc)6 than other forms of the substrate. Molecular modification of SbCDA was conducted based on sequence alignment and homology modeling. A mutant SbCDA63G with higher activity and better temperature stability was obtained. The deacetylation activity of SbCDA63G was increased by 133% compared with the original enzyme, and the optimal reaction temperature increased from 35 to 40 °C. The half-life of SbCDA63G at 40 °C is 15 h, which was 5 h longer than that of the original enzyme. The improved characteristics of the chitin deacetylase SbCDA63G make it a potential candidate to industrially produce chitosan from chitin.

Multi-Dimensional Elimination of ß-Lactams in the Rural Wetland: Molecule Design and Screening for More Antibacterial and Degradable Substitutes.

Restricted economic conditions and limited sewage treatment facilities in rural areas lead to the discharge of small-scale breeding wastewater containing higher values of residual beta-lactam antibiotics (ß-lactams), which seriously threatens the aquatic environment. In this paper, molecular docking and a comprehensive method were performed to quantify and fit the source modification for the combined biodegradation of ß-lactams. Using penicillin (PNC) as the target molecule, combined with contour maps for substitute modification, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed for the high-performance combined biodegradation of ß-lactams. The selected candidate with better environmental friendliness, functionality, and high performance was screened. By using the homology modeling algorithms, the mutant penicillin-binding proteins (PBPs) of Escherichia coli were constructed to have antibacterial resistance against ß-lactams. The molecular docking was applied to obtain the target substitute by analyzing the degree of antibacterial resistance of ß-lactam substitute. The combined biodegradation of ß-lactams and substitute in the constructed wetland (CW) by different wetland plant root secretions was studied using molecular dynamics simulations. The result showed a 49.28% higher biodegradation of the substitutes than PNC when the combined wetland plant species of Eichhornia crassipes, Phragmites australis, and Canna indica L. were employed.

Proteins from pseudocereal seeds: solubility, extraction, and modifications of the physicochemical and techno-functional properties.

Pseudocereals (amaranth, buckwheat and quinoa) are emerging as popular gluten-free crops. This may be attributed to their wide-ranging health benefits, including antioxidant, hypoglycemic and serum-cholesterol reducing properties. Proteins of these crops have a high nutritional quality as a result of the presence of essential amino acids. Additionally, amaranth, buckwheat and quinoa proteins (AP, BP and QP, respectively) have physicochemical properties that are useful for the manufacture of different types of food. However, native pseudocereal proteins demonstrate a low solubility in water, mainly because of their composition. The major components of these proteins are albumins (water-soluble) and globulins (salt-soluble), although some proportions of glutelin (alkali-soluble) and prolamins (alcohol-soluble) are also found. The most commonly used method for extracting pseudocereal proteins is the alkaline extraction method, which may contribute to the low solubility of pseudocereal protein. Fortunately, different methods for modifying physicochemical (or techno-functional) properties have been proposed to extend their industrial application. For example, high-intensity ultrasound (HIUS) proved useful for improving the solubility of API and QP. Heating can allow for the formation of soluble aggregates of QP. The combination of heating and HIUS can improve the digestibility, solubility and foam properties of AP. Conjugation through the Maillard reaction can improve BPI and QP interfacial properties. Thus, present study provides a review of the solubility, extraction and modification of the techno-functional properties of AP, BP and QP. © 2022 Society of Chemical Industry.

Molecular Inhibition for Selective CO2 Conversion.

Electrochemical CO2 reduction presents a sustainable route to the production of chemicals and fuels. Achieving a narrow product distribution with heterogeneous Cu catalysts is challenging and conventional material modifications offer limited control over selectivity. Here, we show that surface-immobilised molecular species can act as inhibitors for specific carbon products to provide rational control over product distributions. Combined experimental and computational results showed that anchoring of a thiol-functionalised pyridine on Cu destabilises a surface-bound reaction intermediate to energetically block a CO-producing pathway, thereby favouring formate production. The nitrogen atom was shown to be essential to the inhibition mechanism. The ability of molecules to control selectivity through inhibition of specific reaction pathways offers a unique approach to rationally modify heterogeneous catalysts.

Modification of Nitrate Ion Enables Stable Solid Electrolyte Interphase in Lithium Metal Batteries.

The lifespan of high-energy-density lithium metal batteries (LMBs) is hindered by heterogeneous solid electrolyte interphase (SEI). The rational design of electrolytes is strongly considered to obtain uniform SEI in working batteries. Herein, a modification of nitrate ion (NO3 - ) is proposed and validated to improve the homogeneity of the SEI in practical LMBs. NO3 - is connected to an ether-based moiety to form isosorbide dinitrate (ISDN) to break the resonance structure of NO3 - and improve the reducibility. The decomposition of non-resonant -NO3 in ISDN enriches SEI with abundant LiNx Oy and induces uniform lithium deposition. Lithium-sulfur batteries with ISDN additives deliver a capacity retention of 83.7 % for 100 cycles compared with rapid decay with LiNO3 after 55 cycles. Moreover, lithium-sulfur pouch cells with ISDN additives provide a specific energy of 319 Wh kg-1 and undergo 20 cycles. This work provides a realistic reference in designing additives to modify the SEI for stabilizing LMBs.

Recent advances and future prospective of organophosphorus-degrading enzymes: identification, modification, and application.

The organophosphorus-based OPs) nerve agents and pesticides have been applied in the agriculture industry for a long time. However, they were found to have a persistent effect on the environment and threaten human health. Traditional methods, including incineration and landfilling, could not thoroughly remove these organophosphorus compounds (OPs). Meanwhile, chemical hydrolysis for decontamination was also inhibited due to the presence of corrosive materials and high costs. Biological remediation for OPs employing microorganisms and organophosphorus-degrading enzymes is promising due to a mild and controllable procedure, environmental-friendly reactions, and high efficacy. A wide variety of enzymes have shown latent ability in degrading OPs hazards like organophosphorus hydrolase (OPH), organophosphorus acid anhydrolase (OPAA), the diisopropylfluorophosphatase (DFPase), and mammalian paraoxonase 1 (PON 1). To this end, increasing efforts have been made on these intriguing enzymes to increase their expression level, enhance the catalytic activity, modify the optimal substrate, and expand the practical application. In this review, the enzyme resource, crystal structure, molecular modification, and industry application were compared and discussed in detail. Moreover, the proposed ideas and positive results could be useful for the other relevant OPs-degrading enzymes.

Alginate degrading enzymes: an updated comprehensive review of the structure, catalytic mechanism, modification method and applications of alginate lyases.

Alginate, a kind of linear acidic polysaccharide, consists of α-L-guluronate (G) and ß-D-mannuronate (M). Both alginate and its degradation products (alginate oligosaccharides) possess abundant biological activities such as antioxidant activity, antitumor activity, and antimicrobial activity. Therefore, alginate and alginate oligosaccharides have great value in food, pharmaceutical, and agricultural fields. Alginate lyase can degrade alginate into alginate oligosaccharides via the ß-elimination reaction. It plays an important role in marine carbon recycling and the deep utilization of brown algae. Elucidating the structural features of alginate lyase can improve our knowledge of its catalytic mechanisms. With the development of structural analysis techniques, increasing numbers of alginate lyases have been characterized at the structural level. Hence, it is essential and helpful to summarize and discuss the up-to-date findings. In this review, we have summarized progress on the structural features and the catalytic mechanisms of alginate lyases. Furthermore, the molecular modification strategies and the applications of alginate lyases have also been discussed. This comprehensive information should be helpful to expand the applications of alginate lyases.

Modified organophosphorus fire retardant with low toxicity/high flame retardancy using the pharmacophore model associated with Mamdani fuzzy inference approach.

The bi-directional selective low toxicity/high flame retardancy organophosphorus fire retardants (OPFRs) derivatives were designed by a comprehensive effect 3D quantitative structure-activity relationship (QSAR) pharmacophore model, and the toxicity and flame retardancy mechanism of OPFR derivatives were explored. The 3D-QSAR comprehensive pharmacophore model was constructed using the toxicity/flame retardancy comprehensive evaluation values of OPFRs for molecular modifications, which were obtained by the Mamdani fuzzy inference approach. The environment-friendly OPFR derivatives (CDPP-F, CDPP-NO2, TPHP-F, TDCIPP-CH2CH3, and TDCIPP-Br) with high flame retardancy showed significantly reduced multi-toxicity effects (biotoxicity, reproductive toxicity, and neurotoxicity) in the comprehensive model. The spatial overlapping volumes of the toxicity/flame retardancy comprehensive effect model with the toxic effect and with flame retardant effect were 1 : 1. The trend (1 : 1) was similar to the degree of improvement of toxicity and flame retardancy of the OPFR derivatives. The toxicity and flame retardancy were decreased by more than 50%. This indicated that the spatial overlapping volumes in the comprehensive model with the toxic and flame retardant mono-models have significant effects. Based on the 2D-QSAR model, molecular docking, and density functional theory, it was found that, in molecular modification, the introduction of electronegative groups to improve the electronic parameters (q+) can reduce the toxicity of OPFRs. An increase in the bond length and bond angle of the molecular side chain increased the steric parameter (MR) that improved the molecular flame retardancy of OPFRs.

An adjusted 3D-QSAR model for the combined activity of fluoroquinolones photodegradation and microbial degradation assisted by dynamic simulation and its application in molecular modification.

This study developed a comprehensive characterization method for the combined degradation effect of modified fluoroquinolones (FQs) photodegradation and microbial degradation. A combination of revised 3D-QSAR model, molecular docking, path simulation inference, pharmacokinetics, molecular dynamics (MD) simulation and toxicokinetics simulation was used to construct a systematic environment-friendly drug screening system. Five derivatives were screened with significantly improved combined degradation effect (over 20%) and functional characteristics and human health parameters through combined model verification, functional and human health risk assessment. The simulation path of photo- and microbial-degradation of gatifloxacin and new gatifloxacin molecules was derived, and the reaction energy barrier was also calculated. The ratio of the total rate-determining steps change rate of the decreased energy barrier (14.10%:26.30%) was consistent with the ratio of the increased degradation performance predicted by the model (22.87%:19.77%), demonstrating the reliability of revised 3D-QSAR model and it could be applied in molecular modification. MD and toxicokinetics simulation were used to predict the binding energy and aquatic toxicity between photo- and microbial-degradation products and the degradation enzymes, which further to screen the degradation pathways with low potential environmental risks. The findings will be helpful to screen environment-friendly drug and develop appropriate strategies for its risk management.

Enzyme Therapy: Current Challenges and Future Perspectives.

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.

Molecular Modifications and Control of Processes to Facilitate the Synergistic Degradation of Polybrominated Diphenyl Ethers in Soil by Plants and Microorganisms Based on Queuing Scoring Method.

In this paper, a combination of modification of the source and regulation of the process was used to control the degradation of PBDEs by plants and microorganisms. First, the key proteins that can degrade PBDEs in plants and microorganisms were searched in the PDB (Protein Data Bank), and a molecular docking method was used to characterize the binding ability of PBDEs to two key proteins. Next, the synergistic binding ability of PBDEs to the two key proteins was evaluated based on the queuing integral method. Based on this, three groups of three-dimensional quantitative structure-activity relationship (3D-QSAR) models of plant-microbial synergistic degradation were constructed. A total of 30 PBDE derivatives were designed using BDE-3 as the template molecule. Among them, the effect on the synergistic degradation of six PBDE derivatives, including BDE-3-4, was significantly improved (increased by more than 20%) and the environment-friendly and functional evaluation parameters were improved. Subsequently, studies on the synergistic degradation of PBDEs and their derivatives by plants and microorganisms, based on the molecular docking method, found that the addition of lipophilic groups by modification is beneficial to enhance the efficiency of synergistic degradation of PBDEs by plants and microorganisms. Further, while docking PBDEs, the number of amino acids was increased and the binding bond length was decreased compared to the template molecules, i.e., PBDE derivatives could be naturally degraded more efficiently. Finally, molecular dynamics simulation by the Taguchi orthogonal experiment and a full factorial experimental design were used to simulate the effects of various regulatory schemes on the synergistic degradation of PBDEs by plants and microorganisms. It was found that optimal regulation occurred when the appropriate amount of carbon dioxide was supplied to the plant and microbial systems. This paper aims to provide theoretical support for enhancing the synergistic degradation of PBDEs by plants and microorganisms in e-waste dismantling sites and their surrounding polluted areas, as well as, realize the research and development of green alternatives to PBDE flame retardants.