MDPI Collection

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12588/185

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Plasma-Assisted One-Step Direct Methanol Conversion to Ethylene Glycol and Hydrogen: Process Intensification
(2024-06-29) Ayodele, Olumide Bolarinwa
This perspective reports a process intensification strategy that converts methanol into ethylene glycol (MeOH-2-EG) in a single step to circumvent multi-step naphtha cracking into ethylene followed by ethylene epoxidation to ethylene oxide (EO) and the subsequent hydrolysis of EO to ethylene glycol (EG). Due to the thermodynamic restriction for the direct MeOH-2-EG, plasma-assisted catalysis was introduced, and platinum group metals were identified as prospective transition metal catalysts that can achieve the formation of strong metal hydride bonds and guarantee the controlled C–C coupling of two plasma-activated hydroxymethyl radicals (*CH₂OH) from methanol, both of which are essential for the single-step MeOH-2-EG.
On the Boundary Value Problems of Hadamard Fractional Differential Equations of Variable Order via Kuratowski MNC Technique
(2021-05-17) Refice, Ahmed; Souid, Mohammed Said; Stamova, Ivanka
In this manuscript, we examine both the existence and the stability of solutions of the boundary value problems of Hadamard-type fractional differential equations of variable order. New outcomes are obtained in this paper based on the Darbo’s fixed point theorem (DFPT) combined with Kuratowski measure of noncompactness (KMNC). We construct an example to illustrate the validity of the observed results.
Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?
(2024-03-31) Høilund-Carlsen, Poul F.; Alavi, Abass; Castellani, Rudolph J.; Neve, Rachael L.; Perry, George; Revheim, Mona-Elisabeth; Barrio, Jorge R.
The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.
Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?
(2024-03-31) Høilund-Carlsen, Poul F.; Alavi, Abass; Castellani, Rudolph J.; Neve, Rachael L.; Perry, George; Revheim, Mona-Elisabeth; Barrio, Jorge R.
The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.
Balancing Sustainability: An Analysis of Habitat for Humanity Affiliates in Mississippi
(2024-02-15) Doleac, Alex; Langar, Sandeep; Sulbaran, Tulio
Non-profit organizations (NPOs) support economically disadvantaged communities by improving housing conditions and building homes, despite limited resources. With rising housing costs and poverty causing homelessness and poor housing quality, NPOs’ efforts are crucial. However, operating constraints (such as financial, policy, and others), often lead NPOs to prioritize initial costs over sustainability and environmental impacts. Therefore, this research investigated the adoption, implementation, and routinization patterns for sustainability and green efforts in Mississippi (US) by a leading NPO. The research used a two-phased combined design methodology, with the first phase involving explorative design that involved the identification of criteria that led to selecting the affiliates of Habitat for Humanity (HFH) as the unit of analysis. The selected NPO (HFH) had 38 affiliates across Mississippi, US, at the time of the study. The second phase involved a cross-sectional design, with data collected by utilizing a structured telephone survey. All collected data were subjected to descriptive and inferential statistics, and thematic analysis. Twenty-five affiliates (66% response rate) participated in the study, and the results indicate that a small proportion of affiliates were actively adopting sustainability practices for projects constructed, and most were located in the southern part of the state. The research identified factors that lead to the routinization of sustainability practices, the most commonly used third-party benchmarking tools, and perceptions of NPOs towards such tools to evaluate the greenness of residential projects. Some crucial implications were identifying uneven project completion within HFH, limited adoption of green strategies, and perception of green certification as non-vital.
Synergism of Fuzzy Leaky Bucket with Virtual Buffer for Large Scale Social Driven Energy Allocation in Emergencies in Smart City Zones
(2024-02-14) Alamaniotis, Miltiadis; Alexiou, Michail
Smart cities can be viewed as expansive systems that optimize operational quality and deliver a range of services, particularly in the realm of energy management. Identifying energy zones within smart cities marks an initial step towards ensuring equitable energy distribution driven by factors beyond energy considerations. This study introduces a socially oriented methodology for energy allocation during emergencies, implemented at the zone level to address justice concerns. The proposed method integrates a fuzzy leaky bucket model with an energy virtual buffer, leveraging extensive data from diverse city zones to allocate energy resources during emergent situations. By employing fuzzy sets and rules, the leaky bucket mechanism distributes buffered energy to zones, aiming to maximize energy utilization while promoting social justice principles. Evaluation of the approach utilizes consumption data from simulated smart city zones during energy-constrained emergencies, comparing it against a uniform allocation method. Results demonstrate the socially equitable allocation facilitated by the proposed methodology.
Experimental Thermal Conductivity Studies of Agar-Based Aqueous Suspensions with Lignin Magnetic Nanocomposites
(2024-02-10) Gautam, Bishal; Nabat Al-Ajrash, Saja M.; Hasan, Mohammad Jahid; Saini, Abhishek; Watzman, Sarah J.; Ureña-Benavides, Esteban; Vasquez-Guardado, Erick S.
Nanoparticle additives increase the thermal conductivity of conventional heat transfer fluids at low concentrations, which leads to improved heat transfer fluids and processes. This study investigates lignin-coated magnetic nanocomposites (lignin@Fe₃O₄) as a novel bio-based magnetic nanoparticle additive to enhance the thermal conductivity of aqueous-based fluids. Kraft lignin was used to encapsulate the Fe₃O₄ nanoparticles to prevent agglomeration and oxidation of the magnetic nanoparticles. Lignin@Fe₃O₄ nanoparticles were prepared using a pH-driven co-precipitation method with a 3:1 lignin to magnetite ratio and characterized by X-ray diffraction, FT-IR, thermogravimetric analysis, and transmission electron microscopy. The magnetic properties were characterized using a vibrating sample magnetometer. Once fully characterized, lignin@Fe₃O₄ nanoparticles were dispersed in aqueous 0.1% w/v agar–water solutions at five different concentrations, from 0.001% w/v to 0.005% w/v. Thermal conductivity measurements were performed using the transient line heat source method at various temperatures. A maximum enhancement of 10% in thermal conductivity was achieved after adding 0.005% w/v lignin@Fe₃O₄ to the agar-based aqueous suspension at 45 °C. At room temperature (25 °C), the thermal conductivity of lignin@Fe₃O₄ and uncoated Fe₃O₄ agar-based suspensions was characterized at varying magnetic fields from 0 to 0.04 T, which were generated using a permanent magnet. For this analysis, the thermal conductivity of lignin magnetic nanosuspensions initially increased, showing a 5% maximum peak increase after applying a 0.02 T magnetic field, followed by a decreasing thermal conductivity at higher magnetic fields up to 0.04 T. This result is attributed to induced magnetic nanoparticle aggregation under external applied magnetic fields. Overall, this work demonstrates that lignin-coated Fe₃O₄ nanosuspension at low concentrations slightly increases the thermal conductivity of agar aqueous-based solutions, using a simple permanent magnet at room temperature or by adjusting temperature without any externally applied magnetic field.
Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification
(2024-02-05) Mendoza Barker, Matthew; Saeger, Sarah; Campuzano, Althea; Yu, Jieh-Juen; Hung, Chiung-Yu
Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD₁₀₀ < 100 spores). However, the Galleria model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that Coccidioides posadasii can convert and complete the parasitic cycle within the hemocoel of the Galleria larva. In Galleria, the LD₁₀₀ is between 0.5 and 1.0 × 10⁶ viable spores for the clinical isolate Coccidioides posadasii C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against Coccidioides. Additionally, we utilized this larva model to screen a Coccidioides posadasii mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that Galleria larvae can be applied as a model for studying Coccidioides infection.
Therapeutic Delivery of Soluble Fractalkine Ameliorates Vascular Dysfunction in the Diabetic Retina
(2024-01-31) Rodriguez, Derek; Church, Kaira A.; Smith, Chelsea T.; Vanegas, Difernando; Cardona, Sandra M.; Muzzio, Isabel A.; Nash, Kevin R.; Cardona, Astrid E.
Diabetic retinopathy (DR)-associated vision loss is a devastating disease affecting the working-age population. Retinal pathology is due to leakage of serum components into retinal tissues, activation of resident phagocytes (microglia), and vascular and neuronal damage. While short-term interventions are available, they do not revert visual function or halt disease progression. The impact of microglial inflammatory responses on the neurovascular unit remains unknown. In this study, we characterized microglia–vascular interactions in an experimental model of DR. Early diabetes presents activated retinal microglia, vascular permeability, and vascular abnormalities coupled with vascular tortuosity and diminished astrocyte and endothelial cell-associated tight-junction (TJ) and gap-junction (GJ) proteins. Microglia exclusively bind to the neuronal-derived chemokine fractalkine (FKN) via the CX3CR1 receptor to ameliorate microglial activation. Using neuron-specific recombinant adeno-associated viruses (rAAVs), we therapeutically overexpressed soluble (sFKN) or membrane-bound (mFKN) FKN using intra-vitreal delivery at the onset of diabetes. This study highlights the neuroprotective role of rAAV-sFKN, reducing microglial activation, vascular tortuosity, fibrin(ogen) deposition, and astrogliosis and supporting the maintenance of the GJ connexin-43 (Cx43) and TJ zonula occludens-1 (ZO-1) molecules. The results also show that microglia–vascular interactions influence the vascular width upon administration of rAAV-sFKN and rAAV-mFKN. Administration of rAAV-sFKN improved visual function without affecting peripheral immune responses. These findings suggest that overexpression of rAAV-sFKN can mitigate vascular abnormalities by promoting glia–neural signaling. sFKN gene therapy is a promising translational approach to reverse vision loss driven by vascular dysfunction.
Dietary Supplementation with 23-Hydroxy Ursolic Acid Reduces the Severity and Incidence of Acute Experimental Autoimmune Encephalomyelitis (EAE) in a Murine Model of Multiple Sclerosis
(2024-01-25) Asmis, Reto; Medrano, Megan T.; Chase Huizar, Carol; Griffith, Wendell P.; Forsthuber, Thomas G.
23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2% wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between the groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN-γ between 23-OH UA-fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T cell responses. In summary, our findings in EAE mice strongly suggest that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing–remitting MS.
A Recombinant Multivalent Vaccine (rCpa1) Induces Protection for C57BL/6 and HLA Transgenic Mice against Pulmonary Infection with Both Species of Coccidioides
(2024-01-09) Campuzano, Althea; Pentakota, Komali Devi; Liao, Yu-Rou; Zhang, Hao; Wiederhold, Nathan P.; Ostroff, Gary R.; Hung, Chiung-Yu
Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against five highly virulent isolates of Cp and Ci. There are total of seven amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with an rCpa1 vaccine had a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post challenge. These data suggest that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses.
A Spectral/hp-Based Stabilized Solver with Emphasis on the Euler Equations
(2024-01-08) Ranjan, Rakesh; Catabriga, Lucia; Araya, Guillermo
The solution of compressible flow equations is of interest with many aerospace engineering applications. Past literature has focused primarily on the solution of Computational Fluid Dynamics (CFD) problems with low-order finite element and finite volume methods. High-order methods are more the norm nowadays, in both a finite element and a finite volume setting. In this paper, inviscid compressible flow of an ideal gas is solved with high-order spectral/hp stabilized formulations using uniform high-order spectral element methods. The Euler equations are solved with high-order spectral element methods. Traditional definitions of stabilization parameters used in conjunction with traditional low-order bilinear Lagrange-based polynomials provide diffused results when applied to the high-order context. Thus, a revision of the definitions of the stabilization parameters was needed in a high-order spectral/hp framework. We introduce revised stabilization parameters, τsupg, with low-order finite element solutions. We also reexamine two standard definitions of the shock-capturing parameter, δ: the first is described with entropy variables, and the other is the YZβ parameter. We focus on applications with the above introduced stabilization parameters and analyze an array of problems in the high-speed flow regime. We demonstrate spectral convergence for the Kovasznay flow problem in both L1 and L2 norms. We numerically validate the revised definitions of the stabilization parameter with Sod’s shock and the oblique shock problems and compare the solutions with the exact solutions available in the literature. The high-order formulation is further extended to solve shock reflection and two-dimensional explosion problems. Following, we solve flow past a two-dimensional step at a Mach number of 3.0 and numerically validate the shock standoff distance with results obtained from NASA Overflow 2.2 code. Compressible flow computations with high-order spectral methods are found to perform satisfactorily for this supersonic inflow problem configuration. We extend the formulation to solve the implosion problem. Furthermore, we test the stabilization parameters on a complex flow configuration of AS-202 capsule analyzing the flight envelope. The proposed stabilization parameters have shown robustness, providing excellent results for both simple and complex geometries.
Development of Intensity–Duration–Frequency (IDF) Curves over the United Arab Emirates (UAE) Using CHIRPS Satellite-Based Precipitation Products
(2023-12-20) Alsumaiti, Tareefa S.; Hussein, Khalid A.; Ghebreyesus, Dawit T.; Petchprayoon, Pakorn; Sharif, Hatim O.; Abdalati, Waleed
The recent flooding events in the UAE have emphasized the need for a reassessment of flood frequencies to mitigate risks. The exponential urbanization and climatic changes in the UAE require a reform for developing and updating intensity–duration–frequency (IDF) curves. This study introduces a methodology to develop and update IDF curves for the UAE at a high spatial resolution using CHIRPS (Climate Hazards Group InfraRed Precipitation with Station) data. A bias correction was applied to the CHIRPS data, resulting in an improved capture of extreme events across the country. The Gumbel distribution was the most suitable theoretical distribution for the UAE, exhibiting a strong fit to the observed data. The study also revealed that the CHIRPS-derived IDF curves matched the shape of IDF curves generated using rain gauges. Due to orographic rainfall in the northeastern region, the IDF intensities were at their highest there, while the aridity of inland regions resulted in the lowest intensities. These findings enhance our understanding of rainfall patterns in the UAE and support effective water resource management and infrastructure planning. This study demonstrates the potential of the CHIRPS dataset for IDF curve development, emphasizes the importance of performing bias corrections, and recommends tailoring adjustments to the intended application.
A p-Refinement Method Based on a Library of Transition Elements for 3D Finite Element Applications
(2023-12-14) Shahriar, Adnan; Mostafa, Ahmed Jenan
Wave propagation or acoustic emission waves caused by impact load can be simulated using the finite element (FE) method with a refined high-fidelity mesh near the impact location. This paper presents a method to refine a 3D finite element mesh by increasing the polynomial order near the impact location. Transition elements are required for such a refinement operation. Three protocols are defined to implement the transition elements within the low-order FE mesh. Due to the difficulty of formulating shape functions and verification, there are no transition elements beyond order two in the current literature for 3D elements. This paper develops a complete set of transition elements that facilitate the transition from first- to fourth-order Lagrangian elements, which facilitates mesh refinement following the protocols. The shape functions are computed and verified, and the interelement compatibility conditions are checked for each element case. The integration quadratures and shape function derivative matrices are also computed and made readily available for FE users. Finally, two examples are presented to illustrate the applicability of this method.
Introduction to the Special Issue Social Meanings of Language Variation in Spanish
(2023-12-06) Barnes, Sonia; Chappell, Whitney
Centering stances, positionalities, and style, the third wave of sociolinguistic study positions individuals at the heart of its analysis [...]
Irradiation of ZnPPIX Complexed with Bovine β-Lactoglobulin Causes Chemical Modifications and Conformational Changes of the Protein
(2023-11-29) Albalawi, Abdullah; Castillo, Omar; Denton, Michael L.; Rickman, John Michael; Noojin, Gary D.; Brancaleon, Lorenzo
Photosensitization of proteins mediated by chromophores is a mechanism commonly employed by nature and mimicked in a broad array of laboratory research and applications. Nature has evolved specialized complexes of proteins and photosensitizers (PS) that assemble to form photoreceptor proteins (PRP). These are used by many organisms in diverse processes, such as energy conversion, protection against photodamage, etc. The same concept has been used in laboratory settings for many applications, such as the stimulation of neurons or the selective depletion of proteins in a signaling pathway. A key issue in laboratory settings has been the relationship between the photooxidation of proteins and conformational changes in host proteins. For several years, we have been interested in creating non-native PRP using porphyrin PS. In this study, we investigated the self-assembled complex between zinc protoporphyrin IX (ZnPPIX) and bovine β-lactoglobulin (BLG) as a model of non-native PRP. Since BLG undergoes a significant conformational transition near physiological pH, the study was carried out at acidic (pH 5) and alkaline (pH 9) conditions where the two conformations are respectively prevalent. We employed a series of steady-state and time-resolved optical spectroscopies as well as gel electrophoresis to experimentally characterize the photosensitization mechanisms and their effect on the host protein. Our results show that ZnPPIX prompts light-dependent modifications of BLG, which appear to be much more significant at alkaline pH. The modifications seem to be driven by photooxidation of amino acid residues that do not lead to the formation of cross-links or protein fragmentation.
Impulsive Controllers Design for the Practical Stability Analysis of Gene Regulatory Networks with Distributed Delays
(2023-11-29) Cao, Jinde; Stamov, Trayan; Stamov, Gani; Stamova, Ivanka
This paper studies gene regulatory networks (GRNs) with distributed delays. The essential concept of practical stability of the genes is introduced. We investigate the problems of practical stability and global practical exponential stability of the GRN model under an impulsive control. New practical stability criteria are proposed by designing appropriate impulsive controllers via the Lyapunov functions approach. In the design of the impulsive controller, we consider the effect of impulsive perturbations at fixed times and distributed delays on the stability of the considered GRNs. Several numerical examples are also presented to justify the proposed criteria.
Advances in Fractional-Order Neural Networks, Volume II
(2023-11-29) Stamova, Ivanka; Stamov, Gani; Li, Xiaodi
Fractional-order neural network models have become an active research subject and have attracted increasing attention in many fields [...]
Inactivating Host Bacteria for Characterization and Use of Phages
(2023-09-27) Chambers, James P.; Wright, Elena T.; Hunter, Barbara; Serwer, Philip
Phage characterization for research and therapy can involve newly isolated phages propagated in pathogenic bacteria. If so, characterization requires safety-managing the bacteria. In the current study, we adapt a common and inexpensive reagent, PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA), to safety-manage bacteria in 20 min by selectively inactivating the bacteria. No bacterial survivors are observed among >10⁹ bacteria per ml for a representative of both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Bacillus thuringiensis). This procedure causes no detected inactivation of podophage T3, myophage T4 and siphophage 0105phi7-2. Margins of safety for PrimeStore concentration exist for bacterial inactivation and phage non-inactivation. Thus, general applicability is expected. Subsequent dialysis is used to block long-term effects on phages. Nonetheless, comparable tests should be performed for each pathogenic bacterial strain/phage. Electron microscopy of thin sections reveals inactivation-altered bacterial cytoplasm and a non-disintegrated bacterial envelope (ghosts). Ghosting of E. coli includes re-arrangement of the cytoplasm and the release of endotoxin. The activity of the released endotoxin is >99% reduced after subsequent dialysis, which also removes PrimeStore components. Ghosting of B. thuringiensis includes apparent phase separation within the cytoplasm. The primary application envisaged is biophysical and other screening of phages for therapy of infectious disease.
Tetrahydrocurcumin Derivatives Enhanced the Anti-Inflammatory Activity of Curcumin: Synthesis, Biological Evaluation, and Structure–Activity Relationship Analysis
(2023-11-26) González, Yisett; Mojica-Flores, Randy; Moreno-Labrador, Dilan; Pecchio, Marisín; Rao, K. S. Jagannatha; Ahumedo-Monterrosa, Maicol; Fernández, Patricia L.; Larionov, Oleg V.; Lakey-Beitia, Johant
Tetrahydrocurcumin, the most abundant curcumin transformation product in biological systems, can potentially be a new alternative therapeutic agent with improved anti-inflammatory activity and higher bioavailability than curcumin. In this article, we describe the synthesis and evaluation of the anti-inflammatory activities of tetrahydrocurcumin derivatives. Eleven tetrahydrocurcumin derivatives were synthesized via Steglich esterification on both sides of the phenolic rings of tetrahydrocurcumin with the aim of improving the anti-inflammatory activity of this compound. We showed that tetrahydrocurcumin (2) inhibited TNF-α and IL-6 production but not PGE₂ production. Three tetrahydrocurcumin derivatives inhibited TNF-α production, five inhibited IL-6 production, and three inhibited PGE₂ production_. The structure–activity relationship analysis suggested that two factors could contribute to the biological activities of these compounds: the presence or absence of planarity and their structural differences. Among the tetrahydrocurcumin derivatives, cyclic compound 13 was the most active in terms of TNF-α production, showing even better activity than tetrahydrocurcumin. Acyclic compound 11 was the most effective in terms of IL-6 production and retained the same effect as tetrahydrocurcumin. Moreover, acyclic compound 12 was the most active in terms of PGE₂ production, displaying better inhibition than tetrahydrocurcumin. A 3D-QSAR analysis suggested that the anti-inflammatory activities of tetrahydrocurcumin derivatives could be increased by adding bulky groups at the ends of compounds 2, 11, and 12.

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