Active Sites Research Articles

Strategies and Mechanisms to Improve the Catalytic Performance of Cu-Based Catalyst for CO2 Electrochemical Reduction Reaction to Methane

This article introduces three significant ways of producing methane by electrocatalytic reduction of carbon dioxide. Electrocatalytic reduction of carbon dioxide can efficiently convert CO2 molecules into various high-energy fuels under ambient conditions. Methane gas, among them, stands out due to its relatively high calorific value, chemical stability, ease of storage and transportation. Therefore, research on electrocatalytic reduction of CO2 to generate methane is crucial. Common methods include adjusting catalyst morphology to expose more active sites, building nanoscale catalysts results in smaller-sized nanostructured copper and combining copper with other metals to form alloys, creating multi-metal catalysts. By optimizing these catalysts, we can efficiently reduce carbon dioxide into methane.

Kinetic Studies on MB Adsorption by Graphene like Material from Coconut Shell Charcoal

Coconut shell (CS) activated carbon is widely used for water purification, but its adsorption capacity is inferior compare to graphene oxide (GO). GO has oxygen functional groups so it can effectively bind pollutants like methylene blue (MB). In this study we synthesized graphene-like material from CS charcoal using the modified Hummers method by varying its oxidation times. The XRD decomposition results for H-CS3.2 show a structural composition similar to GO material. The diffraction peak at 10.7° (3.04%) falls within GO's characteristic range of 8°-11°, supported by a Raman ID/IG ratio of 0.95. In contrast, H-CS3.1 material does not exhibit GO's structural composition, with a diffraction peak at 13.9° (1.09%). An increasing of oxidation time, enhanced adsorption capacity in the equilibrium state of H-CS3.2 (22.368 mg/g) surpassing H-CS3.1 (17.079 mg/g). The heightened adsorption was linked to an increased O/C ratio or higher % of atomic oxygen (0.04 for H-CS3.1 and 0.17 for H-CS3.2). The pseudo second-order Ho (PSO) adsorption kinetic model demonstrated the adsorption mechanism, with active sites (oxygen functional groups) such as carbonyl (C = O) and epoxy (C – O) at basal plane carbon. Steric hindrance caused by hydroxyl functional groups (C – OH) led to a reduction in π-π interactions and decreased adsorption ability of the H-CS3.1 material. Desorption of H-CS3.1 material was influenced by MB detachment through interface diffusion.

Aluminum Fluorides as Noncovalent Lewis Acids in Proteins: The Case of Phosphoryl Transfer Enzymes.

The Protein Data Bank (PDB) was scrutinized for the presence of noncovalent O ⋅ ⋅ ⋅ Al Triel Bonding (TrB) interactions, involving protein residues (e. g. GLU and GLN), adenosine/guanine diphosphate moieties (ADP and GDP), water molecules and two aluminum fluorides (AlF3 and AlF4 -). The results were statistically analyzed, revealing a vast number of O ⋅ ⋅ ⋅ Al contacts in the active sites of phosphoryl transfer enzymes, with a marked directionality towards the Al σ-/π-hole. The physical nature of the TrBs studied herein was analyzed using Molecular Electrostatic Potential (MEP) maps, the Quantum Theory of Atoms in Molecules (QTAIM), the Non Covalent Interaction plot (NCIplot) visual index and Natural Bonding Orbital (NBO) studies. As far as our knowledge extends, it is the first time that O ⋅ ⋅ ⋅ Al TrBs are analyzed within a biological context, participating in protein trapping mechanisms related to phosphoryl transfer enzymes. Moreover, since they are involved in the stabilization of aluminum fluorides inside the protein's active site, we believe the results reported herein will be valuable for those scientists working in supramolecular chemistry, catalysis and rational drug design.

Carbon-Encapsulated Bimetallic Fe-W-Based Selenides with Abundant Heterogeneous Conductive Network for Superior Potassium Ion Storage.

Potassium-ion batteries (KIBs) are one of the most promising alternatives to lithium-ion batteries (LIBs) due to their high ion mobility, abundant resources, and low cost. However, the problems of low capacity and poor cycling stability of KIBs remain unsolved; therefore, it is crucial to explore alternative electrode materials suitable for reversible insertion and extraction of K+. Herein, carbon-encapsulated Fe3Se4/WSe2 microsphere material assembled from nanosheets with abundant heterogeneous interfaces and expanded interlayer spacing (denoted as FWSC) is designed as an anode material for superior potassium ion storage. The microspheres assembled from nanosheets, the outer carbon coating, and the expanded layer spacing can expose more active sites and improve the electronic conductivity and structural stability of the material. The abundant heterogeneous conductive network not only improves the conductivity of the material but also enhances the reversibility of the electrochemical reaction. As a result, the FWSC exhibits outstanding cycling stability, excellent rate performance (the capacity retention is 53% when the current density is from 0.5 to 1.0 A g-1), and stable long-term cycle performance (a capacity of 209 mAh g-1 at 1.0 A g-1 over 1000 cycles).

Application of the Linear Interaction Energy Method to Nitric Oxide Synthase Structure-Based Inhibitor Design.

The overproduction of nitric oxide by neuronal nitric oxide synthase (nNOS) is associated with several neuropathological conditions. As a result, inhibition of nNOS is a desirable therapeutic goal while avoiding the inhibition of endothelial NOS (eNOS) given its essential role in maintaining cardiovascular tone. Designing inhibitors with high specificity for nNOS over eNOS is challenging given the close similarity in the active site structure of all mammalian NOS isoforms. Computational methods like free energy perturbation (FEP) and thermodynamic integration (TI) offer attractive avenues for rational drug design, but application of these methods to NOS is hindered by several challenges, including proper handling of highly charged inhibitors with diverse structures as well as computational expense. To address these issues, we present a simplified approach combining continuum dielectric generalized born (GB) solvent models with linear interaction energy (LIE) calculations. Our method demonstrates excellent agreement with experimental data for charged inhibitors targeting mammalian NOS isoforms (mNOS). Our results highlight the utility of the GB-LIE method as a promising tool for screening NOS inhibitors and potentially other protein targets with charged active sites and diverse inhibitor structures.

Enhanced Photosensitizer Wettability via Anchoring Competition of Violet Phosphorus Quantum Dots for Breakthroughs in Photodynamic Film Sterilization.

Wettability is important for photodynamic film sterilization since higher wettability enhances the capture of bacteria in contact with photosensitizers. Herein, a small number of violet phosphorus quantum dots (VPQDs) are anchored into hypericin bacterial cellulose films (VP/Hy-BC films) to improve wettability, reducing the water contact angle from 56.8° to 33.0°. This modification facilitated more effective interactions between the bacteria and photosensitizers, rapidly inactivating 7 log10 CFU/mL of Staphylococcus aureus within 60min. First-principles calculations and molecular dynamics simulations reveal that VPQDs, with their low spatial site resistance, reduced the intermolecular Hy self-aggregation force. This increased the solvent-accessible surface area of VP/Hy by ≈25.7%, thereby decreasing hydrophobic photosensitizer aggregation. Consequently, more active sites are exposed, remarkably improving the photoelectron transfer efficiency. VP/Hy-BC demonstrated exceptional efficacy in inhibiting bacterial proliferation; for instance, it extended beef shelf life by up to 10 days. The findings of this study will aid the development of health-conscious, eco-friendly, and efficient antimicrobial packaging films.

Synthesis of Novel 3,4-Dihydropyrimidine Derivatives, Cytotoxic Activity Evaluation, Apoptosis, Molecular Docking Studies, and MD Simulations.

In this study, twelve 3,4-dihydropyrimidines derivatives were synthesized through Biginelli multi-component reaction. The efficacy of these compounds against MCF-7, A549, and HeLa cells was evaluated using the MTT method. The results showed that designed derivatives were more effective against A549 cancer cells than MCF-7 and HeLa cells. Compound 5l (bearing 4-Cl-phenyl at C4 of 3, 4-dihydropyrimidin-2(1H)-one ring) was the most potent analogue (A549: 18.65±1.87 μM, HeLa: 26.59±2.71 μM, MCF-7: 31.82±2.64 μM). The presence of an electron-withdrawing group with optimum lipophilicity at the C4 position of the phenyl ring increased the cytotoxic effect. The flow cytometry findings indicated that compound 5l induced apoptosis in A549 cancer cells in a dose-dependent manner. Eg5 and AKT1 were selected as molecular modeling target by applying pharmacology network analyses. The molecular docking results indicated that both enantiomers of compound 5l had significant interactions with key residues in both Eg5 (Gly117 and Glu116) and AKT1 (Ala123 and Glu121) active sites. However, MD simulation revealed that the R enantiomer had a more stable complex and a higher binding affinity to the Eg5 enzyme active site than the S-enantiomer. The affinity of 5l (R enantiomer) to Eg5 was predicted more than AKT1.

Rational Design of Diatomic Active Sites for Elucidating Oxygen Evolution Reaction Performance Trends

AbstractDiatomic catalysts, especially those with heteronuclear active sites, have recently attracted significant attention for their advantages over single‐atom catalysts in reactions with relatively high energy barrier, e.g. oxygen evolution reaction. Rational design and synthesis of heteronuclear diatomic catalysts are of immense significance but have so far been plagued by the lack of a definitive correlation between structure and catalytic properties. Here, we report macrocyclic precursor constrained strategy to fabricate series of transition metal (MT, Ni, Co, Fe, Mn, or Cu)‐noble (MN, Ir or Ru) centers in carbon material. One notable performance trend is observed in the order of Cu−MN<Mn−MN<Fe−MN<MN<Co−MN<Ni−MN. Meanwhile, the pathway has been not altered, still following the traditional adsorption reaction mechanism. The effect of the MT atoms on the performances could possibly originate from the distinct adsorption/desorption behaviors of key intermediates (i.e. *OH, *O and/or *OOH), strongly implying that ΔG*OOH–ΔG*OH could be used as the performance descriptor. We believe that our work provides useful strategy for synthesis of diatomic active sites with sole coordination configuration and varied composition, and in‐depth insight to their catalytic mechanism, which could be used for further optimization of diatomic catalysts towards oxygen electrocatalysis.

Asymmetric coordinative modulation boosting the activity and thermal stability of Pt1/CeO2 for CO oxidation under harsh condition

Supported metal catalysts play a central role in chemical industry, but it remains a formidable challenge to realize high activity while maintaining atomically dispersed status to maximize atom efficiency under harsh conditions. Herein, a novel strategy of constructing asymmetric coordination Pt active sites via coating N-doped carbon onto ceria supported Pt single atoms (Pt1/CeO2@CN) is proposed, through which superior low-temperature CO oxidation activity and satisfactory thermal stability are achieved simultaneously. Experimental and density functional theory results confirm that the unique asymmetric N2-Pt1-O2 coordinative configuration on Pt1/CeO2@CN tailors the electronic properties of Pt 5d states, increasing the turnover frequency by 15 times for CO oxidation at 120 °C compared with that on Pt1/CeO2 and sustaining the atomically dispersed status of Pt at as high as 400 °C under H2-containing atmosphere. This strategy suggests a promising avenue to fabricating highly active and stable supported metal catalysts for practical applications under harsh conditions.

The Concept of Healing Waterscapes in Public Open Spaces to Construct the Positive Psychology of Visitors

Public open spaces contain various features that have psychological effects on human mental health. Water, as one of the key elements in landscape design, not only enhances aesthetics but also provides sensory stimulation, social interaction, and psychological benefits. It possesses therapeutic qualities that promote relaxation and reduce stress. Given the rising prevalence of mental health issues among adolescents in Bali, public open spaces incorporating waterscapes play a crucial role. The concept of a "healing waterscape" can be applied in such spaces, where environmental elements are strategically designed to improve mental well-being through psychological approaches. However, no clear criteria for healing waterscape design have been formulated, and it remains unclear whether such criteria are being applied in the waterscapes of public open spaces in Denpasar City and Klungkung Regency. This study aims to establish criteria for healing waterscape design in public open spaces and assess the extent to which these criteria are implemented in Denpasar City and Klungkung Regency. Using a mixed-methods data analysis with JMP software, the study identifies four key variables in healing waterscape design: social, behavioral, cognitive, and emotional factors. The design criteria that should be considered for public space waterscapes in Denpasar and Klungkung include activity diversity, site characteristics, spatial variety, acoustics, water shape, movement, flow, lighting and signage, and both biotic and abiotic components.

Reductive Coupling of N-Heteroarenes and 1,2-Dicarbonyls for Direct Access to γ-Amino Acids, Esters, and Ketones Using a Heterogeneous Single-Atom Iridium Catalyst.

Despite their significant importance, the challenges in direct and diverse synthesis of N-heterocyclic γ-amino acids/esters/ketones hamper exploration of their applications. Herein, by developing a multifunctional heterogeneous iridium single-atom catalyst composed of silica-confined iridium species and a boron-doped ZrO2 support (Ir-SAs@B-ZrO2/SiO2), we describe its utility in establishing a new reductive coupling reaction of N-heteroarenes and 1,2-dicarbonyls for selective and diverse construction of the as-described compounds in a straightforward manner. The striking features, including good substrate and functionality tolerance, high step and atom economy, exceptional catalyst reusability, and diversified product post-transformations, highlight the practicality of the developed chemistry. Mechanistic studies reveal that the synergy between the active Ir sites and acidic support favors a chemoselective reduction of the more inert N-heteroarenes and affords requisite enamine intermediates. In this work, the concept on precise transformation of reductive intermediates will open a door to further develop useful tandem reactions by rational catalyst design.

Efficient tetracycline degradation using carbon quantum dot modified TiO2@LaFeO3 hollow core shell photocatalysts

Efficient harnessing of solar energy presents a significant challenge in environmental cleanup efforts. This study develops a highly effective carbon quantum dots-modified hollow core-shell TiO2-LaFeO3 heterojunction photocatalyst (CDs-TLFO). Structural analysis confirmed that nanosheets are loaded with CQDs, forming a hollow core-shell structure with intimate interconnection. Photocatalytic experiments reveal that CDs-TLFO degrads tetracycline hydrochloride (TC) 2.02 times faster than TLFO alone, and significantly outperformes h-TiO2 and LaFeO3 (11.28 and 2.78 times, respectively). This enhancement is attributed to CQDs acting as electron acceptors with upconversion properties, enhancing the separation of e–-h+ pairs and boosting visible light absorption. Integration of CQDs onto the TLFO surface creates numerous active sites and enhances visible light absorption. SEM and TEM tests confirm that the catalyst has a hollow core-shell structure. ESR tests and radical trapping experiments indicate that the high degradation efficiency of the catalyst mainly owns to the synergistic effect of hydroxyl radicals (·OH) and superoxide radicals (·O2−). The reusability and stability of the catalysts are investigated, potential TC degradation pathways are proposed as well as the photocatalytic reaction mechanism is revealed. This research introduces promising avenues for environmental cleanup and offers a straightforward, energy-efficient, and environmentally friendly method for producing CDs-TLFO heterojunction materials with superior photocatalytic capabilities.

Ultrasensitive Room Temperature Formaldehyde Sensors Based on F Doped ZnO Nanostructures Activated by UV Light.

It is urgent to develop an ultrasensitive formaldehyde (HCHO) sensor that can operate at room temperature and has a low detection limit. Metal oxide semiconductors are excellent gas sensitive materials. Therefore, in this paper, we present the synthesis of fluorine (F) doped zinc oxide (ZnO) porous nanomaterials through a straightforward one-pot method with the optimization of F doping levels to achieve the detection of low concentrations of HCHO under UV light at room temperature. Under 375 nm UV light, the sensor exhibits a response value of 386% to 10 ppm of HCHO, which is 2.6 times higher than that of pure ZnO, and its detection limit is as low as 75 ppb. It has excellent selectivity, stability, and moisture resistance, which can meet the requirements of HCHO detection in daily life. Analysis reveals that doping ZnO with F not only increases the material's specific surface area but also introduces active sites. Furthermore, it alters the state of HCHO on the material's surface from physical adsorption to chemical adsorption. The above reasons together enhance the adsorption of HCHO on the gas sensitive material, thereby improving its gas sensitivity performance. Overall, this work demonstrates that F-doped ZnO is a potential material for ultrasensitive HCHO sensors and provides insights into the interpretation of the effect of doping on the gas sensitivity properties of materials.

Tunable Activated Esters Enable Lysine-Selective Protein Labeling and Profiling.

Lysine residues on protein surfaces are abundant and often found in enzyme active sites, making them critical targets for studying undruggable proteins. However, the varied microenvironment surrounding lysine residues results in a wide range of pKa values, complicating site-specific covalent binding. In this study, we address the challenges posed by the diverse reactivity of amino side chains by modulating the amide reaction activity of heteroaromatic activated esters. By fine-tuning the type, position, and number of heteroatoms, we successfully rationalized the regulation of their amide reaction activity, leading to the design of probes for selective lysine labeling within the proteome for profiling purposes. Systematic optimization of these esters' reactivity and selectivity has yielded a series of effective probes suitable for both in vitro and cellular applications. These findings significantly enhance our understanding of protein functions and mechanisms, facilitated by the precise identification and analysis of protein labeling and profiling.

3D NiCoW Metallic Compound Nano-Network Structure Catalytic Material for Urea Oxidation

Urea shows promise as an alternative substrate to water oxidation in electrolyzers, and replacing OER with the Urea Oxidation Reaction (UOR, theoretical potential of 0.37 V vs. RHE) can significantly increase hydrogen production efficiency. Additionally, the decomposition of urea can help reduce environmental pollution. This paper improves the inherent activity of catalytic materials through morphology and electronic modulation by incorporating tungsten (W), which accelerates electron transfer, enhances the electronic structure of neighboring atoms to create a synergistic effect, and regulates the adsorption process of active sites and intermediates. NiCoW catalytic materials with an ultra-thin nanosheet structure were prepared using an ultrasonic-assisted NaBH4 reduction method. The results show that during the OER process, NiCoW catalytic materials have a potential of only 1.53 V at a current density of 10 mA/cm2, while the UOR process under the same conditions requires a lower potential of 1.31 V, demonstrating superior catalytic performance. In a mixed electrolyte of 1 M KOH and 0.5 M urea, overall water splitting also shows excellent performance. Therefore, the designed NiCoW electrocatalyst, with its high catalytic activity, provides valuable insights for enhancing the efficiency of water electrolysis for hydrogen production and holds practical research significance.

DEVELOPMENT OF 1H-INDAZOLE DERIVATIVES AS ANTI-INFLAMMATORY AGENTS USING COMPUTATIONAL METHODS

Objective: Due to the rising prevalence of disorders linked to inflammation, there is a greater emphasis on the discovery and development of anti-inflammatory drugs, with a focus on producing new structural compounds. Methods: In this research, molecular docking and Molecular Dynamics (MD) simulation study were carried out to evaluate the 1H-indazole analogs as potent anti-inflammatory agents. Results: The compounds containing difluorophenyl, para-toulene and 4-methoxyphenyl group shows significant binding results (9.11, 8.80 and 8.46 kcal/mol respectively) when docked with Cyclooxygenase-2 (COX-2) enzyme 3NT1. The results of the MD simulation indicated that test compound BDF was relatively stable in the COX-2 enzymes active sites. The compound BDF-3NT1 demonstrated substantial affinities for binding with all of its aimed targets following a dynamic Molecular Mechanics with Generalized Born Surface Area (MM-GBSA) analysis. Conclusion: In accordance to this study, newly developed 1H-indazole compounds have the potential for treating inflammation.

The influence mechanism of mechanical modification on fly ash carbonation to solidify heavy metals

Dry and wet milling, were selected to carry out modification experiments. The influence of mechanical modification pretreatment on fly ash carbonation to solidify heavy metals was explored, and its influence mechanism was revealed. Mechanical modification can improve the physical properties, and the continuous application of mechanical energy can activate the active sites which strengthen fly ash carbonation. The carbonation efficiency was obtained by 500–800 °C thermogravimetric analysis before and after carbonation. The average carbonation efficiency improved by dry milling is 2.28 %, and that improved by wet milling is 8.11 %. Carbonation has a good curing effect on Cr, Cd, Pb and As, especially when the CO2 is raised to supercritical. At 8 MPa pressure, the leaching concentrations of Cr, Cd, Pb and As decrease by 34.94 %, 7.00 %, 15.28 % and 35.85 %. The stabilization effect of fly ash carbonation on heavy metals is significantly improved after mechanical modification pretreatment. Comparison experiments on characterization of fly ash before and after mechanical modification shows that ball milling significantly increases the specific surface area. The crushing effect of wet milling is better, because the presence of water weakens the agglomeration of fine particles caused by van der Waal force. Mechanical modification can effectively improve the pore structure of fly ash and activate active sites which promote carbonation to form a larger physical wrapping area and strengthen stable carbonate formation. so mechanical modification effectively improves the solidification of heavy metals by carbonation.

Nitrogen-Rich Molybdenum Nitride with Intrinsic CD39 Nucleotidase Activity.

CD39 is one of the important nucleotidases to adjust extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) concentration. However, the enzyme mimics to simulate the activity of CD39 still remains to be explored. Herein nitrogen-rich molybdenum nitride (Mo5N6) nanosheets are explored to possess CD39-like activity, which are able to catalyze the hydrolysis of the high-energy phosphate bonds (HEPBs) in ATP and ADP but not the common phosphate bonds in adenosine monophosphate (AMP). The catalytic hydrolysis of the phosphate bond over Mo5N6-700 nanosheets is first investigated using para-nitrophenyl phosphate as the model substrate and then the CD39-like activity is further explored and verified by 31p NMR spectroscopy. Mo4+ on the surface of Mo5N6-700 nanosheets are the catalytic active sites. Using ATP as the model substrate, the Km and Vmax values of CD39-like activity at optimal pH 9.0 are 3.2µmol L-1 and 18.5µmol L-1 h-1, respectively. The CD39-like activity of Mo5N6-700 nanosheets enabled the down-regulation of intracellular ATP concentration to a larger degree for cancer cells than normal cells, which makes Mo5N6-700 nanosheets a potential therapeutic reagent for cancers.

Synergistic effect of FeOOH cocatalyst and Al2O3 passivation layer on BiVO4 photoanode for enhanced photoelectrochemical water oxidation

BiVO4 is one of the most attractive photoanodes for water oxidation due to its 2.4 eV narrow band gap, suitable band edge position, good stability in aqueous solution, low cost and non-toxicity. However, due to some inherent disadvantages such as low carrier mobility, severe charge recombination and slow water oxidation kinetics, the actual BiVO4 photocurrent density is often lower than the theoretical value of 7.5 mA cm−2. In this paper, BiVO4 was modified by alkali-treated Al2O3 passivation layer and FeOOH, and the photocurrent density of BiVO4 reached an astonishing 3.8 mA cm−2 at 1.23 VRHE, and the ABPE (applied bias photon-to-current efficiency) was close to 1 %. The detailed structural characterization and electrochemical test show that Al2O3 prepared by ALD (atomic layer deposition) can play a role in passivation of BiVO4 surface state after alkali treatment, inhibit electron hole recombination on BiVO4 surface, and accelerate hole transfer. As a hole storage layer and catalyst layer, FeOOH promoted the interfacial hole transfer, increased the active sites at the electrode electrolyte interface, and significantly increased the water oxidation activity. This work provides a novel method to enhance the performance of water electrolysis by using ALD to assist passivation of bismuth vanadate photoanode surface states.

Tailoring d‐Band Center of Single‐Atom Nickel Sites for Boosted Photocatalytic Reduction of Diluted CO2 from Flue Gas

AbstractPhotocatalytic reduction of diluted CO2 from anthropogenic sources holds tremendous potential for achieving carbon neutrality, while the huge barrier to forming *COOH key intermediate considerably limits catalytic effectiveness. Herein, via coordination engineering of atomically scattered Ni sites in conductive metal–organic frameworks (CMOFs), we propose a facile strategy for tailoring the d‐band center of metal active sites towards high‐efficiency photoreduction of diluted CO2. Under visible‐light irradiation in pure CO2, CMOFs with Ni‐O4 sites (Ni‐O4 CMOFs) exhibits an outstanding rate for CO generation of 13.3 μmol h−1 with a selectivity of 94.5 %, which is almost double that of its isostructural counterpart with traditional Ni‐N4 sites (Ni‐N4 CMOFs), outperforming most reported systems under comparable conditions. Interestingly, in simulated flue gas, the CO selectivity of Ni‐N4 CMOFs decreases significantly while that of Ni‐O4 CMOFs is mostly unchanged, signifying the supremacy for Ni‐O4 CMOFs in leveraging anthropogenic diluted CO2. In situ spectroscopy and density functional theory (DFT) investigations demonstrate that O coordination can move the center of the Ni sites′ d‐band closer to the Fermi level, benefiting the generation of *COOH key intermediate as well as the desorption of *CO and hence leading to significantly boosted activity and selectivity for CO2‐to‐CO photoreduction.