Evaluation of the novel ALK5 inhibitor EW-7197 on therapeutic efficacy in renal fibrosis using a three-dimensional chip model.

Background: EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-ß1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial-mesenchymal transition, angiogenesis, and inflammatory cytokine expression. Methods: In a 3D renal fibrosis-on-a-chip model, three cell types (kidney fibroblasts, human proximal tubular cell line, and human umbilical vein endothelial cells) were cultured and treated with TGF-ß1 and EW-7197. Expression of alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis was observed via confocal microscopy, and cytokine levels were measured using real-time polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-ß, and Smad 2/3 were determined, and renal fibrosis was assessed with Masson's trichrome stain. Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-ß fibrosis group. TGF-ß decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-ß-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-ß and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-ß1, TGF-ß3, IL-1ß. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-ß signaling. Conclusion: EW-7197 attenuated the TGF-ß1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Reliable and Robust Two-Dimensional Perovskite Memristors for Flexible-Resistive Random-Access Memory Array.

Two-dimensional (2D) halide perovskites have become a promising class of memristive materials due to their low power consumption, compositional versatility, and microstructural anisotropy in electronics. However, implementing high-performance resistive random-access memory requires a higher reliability and moisture resistance. To address these issues, component studies and attempts to improve the phase stability have been reported but have not been able to achieve sufficient reliability. Here, highly textured thin films grown perpendicular to the substrate in Ruddlesden-Popper 2D perovskites exhibited highly stable and reliable binary memory performance. We further built a flexible crossbar array to verify data storage capability, achieving a high device yield, robust endurance, long retention, reliability to operate under bending conditions, and moisture stability over a year. These device performances are attributed to preformed vertically oriented nanocrystals that allow the conductive filaments to operate reliably. Our finding provides the material design strategy that can be extended to the development of semiconductor materials for next-generation memory devices.

Elucidating Heterogeneous Li Insertion Using Single-Crystalline and Freestanding Layered Oxide Thin Film.

The kinetics of interfacial ion insertion govern the uniformity of electrochemical reactions, playing a crucial role in lithium-ion battery performance. In two-dimensional lithium-conducting layered-oxide battery particles, variation in insertion rates across insertion channels remains unclear due to poorly defined crystal orientation at the solid-liquid interface and solid-state-lithium-diffusion length. This ambiguity complicates understanding inhomogeneous lithium-insertion channels activation. A systematic study requires crystallographically predefined interfaces and in situ lithium-concentration mapping. Here, we fabricated a freestanding, (104)-oriented-LiNi1/3Mn1/3Co1/3O2 single-crystal thin film using dissolution-induced release and performed in situ scanning-transmission-X-ray-microscopy to spatially resolve lithium-insertion at well-defined-interfaces. We observed heterogeneous lithium-concentration evolution due to channel-by-channel insertion rate variation, despite the potential for homogeneous lithium distribution via a solid-solution-phase at equilibrium in NMC111. Increasing current density exacerbates this heterogeneity, highlighting channel-by-channel variation. Our findings provide critical insights into battery electrode utilization and lifetime management, potentially guiding the design of more efficient and durable lithium-ion batteries.

Synthesis of novel composite material with spent coffee ground biochar and steel slag zeolite for enhanced dye and phosphate removal.

Rising concerns over water scarcity, driven by industrialization and urbanization, necessitate the need for innovative solutions for wastewater treatment. This study focuses on developing an eco-friendly and cost-effective biochar-zeolite composite (BZC) adsorbent using waste materials-spent coffee ground biochar (CGB) and steel slag zeolite (SSZ). Initially, the biochar was prepared from spent coffee ground, and zeolite was prepared from steel slag; their co-pyrolysis resulted in novel adsorbent material. Later, the physicochemical characteristics of the BZC were examined, which showed irregular structure and well-defined pores. Dye removal studies were conducted, which indicate that BZC adsorption reach equilibrium in 2 h, exhibiting 95% removal efficiency compared to biochar (43.33%) and zeolite (74.58%). Moreover, the removal efficiencies of the novel BZC composite toward dyes methyl orange (MO) and crystal violet (CV) were found to be 97% and 99.53%, respectively. The kinetic studies performed with the dyes and phosphate with an adsorbent dosage of 0.5 g L-1 suggest a pseudo-second-order model. Additionally, the reusability study of BZC proves to be effective through multiple adsorption and regeneration cycles. Initially, the phosphate removal remains high but eventually decreases from 92% to 70% in the third regeneration cycle, highlighting the robustness of the BZC. In conclusion, this study introduces a promising, cost-effective novel BZC adsorbent derived from waste materials as a sustainable solution for wastewater treatment. Emphasizing efficiency, reusability, and potential contributions to environmentally conscious water treatment, the findings highlight the composite's significance in addressing key challenges for the removal of toxic pollutants from the aqueous solutions. PRACTITIONER POINTS: A novel biochar-zeolite composite (BZC) material has been synthesized. Excellent removal of dyes by BZC (~95%) was achieved as compared to their counterparts The kinetic studies performed suggest a pseudo-second-order model. BZC proves to be highly effective for multiple adsorption studies. Excellent reusability showed potential as a robust adsorbent.

Highly Durable Chemoresistive Micropatterned PdAu Hydrogen Sensors: Performance and Mechanism.

Hydrogen (H2) is a promising alternative energy source for Net-zero, but the risk of explosion requires accurate and rapid detection systems. As the use of H2 energy expands, sensors require high performance in a variety of properties. Palladium (Pd) is an attractive material for H2 detection due to its high H2 affinity and catalytic properties. However, poor stability caused by volume changes and reliability due to environmental sensitivity remain obstacles. This study proposes a micropatterned thin film of PdAu with optimized composition (Pd0.62Au0.38) as a chemoresistive sensor to overcome these issues. At room temperature, the sensor has a wide detection range of 0.0002% to 5% and a fast response time of 9.5 s. Significantly, the sensor exhibits excellent durability for repeated operation (>35 h) in 5% H2 and resistance to humidity and carbon monoxide. We also report a negative resistivity change in PdAu, which is opposite to that of Pd. Density functional theory (DFT) calculations were performed to investigate the resistance change. DFT analysis revealed that H2 penetrates specific interstitial sites, causing partial lattice compression. The lattice compression causes a decrease in electrical resistance. This work is expected to contribute to the development of high-performance H2 sensors using Pd-based alloys.

Real-Time Tunable Gas Sensing Platform Based on SnO2 Nanoparticles Activated by Blue Micro-Light-Emitting Diodes.

Micro-light-emitting diodes (µLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue µLED-integrated light-activated gas sensor array based on SnO2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for µLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH3, H2, and C2H5OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

High-Performance Ferroelectric Thin Film Transistors with Large Memory Window Using Epitaxial Yttrium-Doped Hafnium Zirconium Gate Oxide.

Preventing ferroelectric materials from losing their ferroelectricity over a low thickness of several nanometers is crucial in developing multifunctional nanoelectronics. Epitaxially grown 5 at. % yttrium-doped Hf0.5Zr0.5O2 (YHZO) thin films exhibit an atomically smooth surface, an ability to maintain ferroelectricity even at a thickness of 10 nm, and excellent insulating properties, making them suitable for use as gate oxides in ferroelectric thin film transistors (FeTFTs). Through the epitaxial growth of a YHZO/La0.67Sr0.33MnO3 (LSMO)/SrTiO3 (STO) heterostructure, YHZO effectively retains its ferroelectricity and orthorhombic single phase, leading to enhancing electron mobility (∼19.74 cm2 V-1 s-1) and memory window (3.7 V) in the amorphous InGaZnO4 (a-IGZO)/YHZO/LSMO/STO FeTFTs. These FeTFTs demonstrate a consistent memory function with remarkable endurance (∼106 cycles) and retention (∼104 s). Furthermore, they sustain a constant memory window even under ±6 V bias stress for 104 s and exhibit excellent stability even under ±6 V/1 ms pulse cycling for 107 cycles. For comparison, a transistor with the same structure was fabricated using epitaxial nonferroelectric LaAlO3 (LAO) and epitaxial undoped Hf0.5Zr0.5O2 (HZO) as alternatives to YHZO. This study presents a novel approach to exploit the potential of YHZO in FeTFTs, contributing to the development of next-generation logic-in-memory.

Halide Perovskites-Based Diffusive Memristors for Artificial Mechano-Nociceptive System.

Numerous efforts for emulating organ systems comprised of multiple functional units have driven substantial advancements in bio-realistic electronics and systems. The resistance change behavior observed in diffusive memristors shares similarities with the potential change in biological neurons. Here, the diffusive threshold switching phenomenon in Ag-incorporated organometallic halide perovskites is utilized to demonstrate the functions of afferent neurons. Halide perovskites-based diffusive memristors show a low threshold voltage of ≈0.2 V with little variation, attributed to the facile migration of Ag ions uniformly dispersed within the halide matrix. Based on the reversible and reliable volatile threshold switching, the memristors successfully demonstrate fundamental nociceptive functions including threshold firing, relaxation, and sensitization. Furthermore, to replicate the biological mechano-nociceptive phenomenon at a system level, an artificial mechano-nociceptive system is built by integrating a diffusive memristor with a force-sensing resistor. The presented system is capable of detecting and discerning the detrimental impact caused by a heavy steel ball, effectively exhibiting the corresponding sensitization response. By further extending the single nociceptive system into a 5 × 5 array, successful stereoscopic nociception of uneven impulses is achieved in the artificial skin system through array-scale sensitization. These results represent significant progress in the field of bio-inspired electronics and systems.

Intraoperative Hypotension Prediction Based on Features Automatically Generated Within an Interpretable Deep Learning Model.

The monitoring of arterial blood pressure (ABP) in anesthetized patients is crucial for preventing hypotension, which can lead to adverse clinical outcomes. Several efforts have been devoted to develop artificial intelligence-based hypotension prediction indices. However, the use of such indices is limited because they may not provide a compelling interpretation of the association between the predictors and hypotension. Herein, an interpretable deep learning model is developed that forecasts hypotension occurrence 10 min before a given 90-s ABP record. Internal and external validations of the model performance show the area under the receiver operating characteristic curves of 0.9145 and 0.9035, respectively. Furthermore, the hypotension prediction mechanism can be physiologically interpreted using the predictors automatically generated from the proposed model for representing ABP trends. Finally, the applicability of a deep learning model with high accuracy is demonstrated, thus providing an interpretation of the association between ABP trends and hypotension in clinical practice.

Correlation between Cellular Structure Morphology and Anisotropic Yield in Additively Manufactured Stainless Steel 316L.

Additively manufactured austenitic stainless steel 316L is composed of a cellular structure, which has a directionality, and is observed with a different morphology depending on the observation direction. The cellular structure morphology that appears with a high probability in grains with a specific grain orientation is determined. Taylor factor, which is calculated by considering grain orientation, is related to cellular structure morphology due to the directional cellular structure in additively manufactured austenitic stainless steel 316L. The Taylor factor affects the mechanical properties. The yield strength of additively manufactured SUS316L can be explained by the correlation between cellular structure morphology, grain orientation, and Taylor factor.

Microstructural Control Strategy Based on Optimizing Laser Powder Bed Fusion for Different Hastelloy X Powder Size.

In additive manufacturing (AM), the powder properties and laser powder bed fusion (LPBF) process parameters influence the quality of materials and building parts. However, the relationship between the size of the powder, LPBF process parameters, and mechanical properties is not well-established. In addition, Hastelloy X (HX) is attracting attention for its excellent high-temperature properties, but it is difficult to process, such as by cutting and milling, because of its high hardness and high ductility. This can be overcome by applying the AM process. We compared the LPBF window process maps for two HX powders of different sizes. Despite their small difference of 19.7% in particle size, it was confirmed that the difference in laser power was more than 40 W, the difference in scan speed was more than 100 mm/s, and the difference in energy density was more than 20% under the optimal process conditions. The as-built specimen had a larger molten-pool size as the energy density was higher, which resulted in the differences in mechanical properties at room temperature and high temperature (816 °C). We considered the control of the size of the powder to obtain the properties required for each temperature condition. The microstructures and mechanical properties of the as-built LPBF specimens were also investigated and compared with those of cast HX. Because of the rapid melting and solidification processes in LPBF, the as-built HX exhibited nano-sized dendrite structures and large internal strain energy. This resulted in the as-built LPBF exhibiting a higher room-temperature tensile strength than the cast material. Under high-temperature conditions, the grain boundary of the as-built LPBF acts as a sliding path, and the as-built LPBF HX showed significantly better high-temperature tensile strength characteristics than the cast HX.

Gas transfer model for a multistage vortex aerator: A novel oxygen transfer system for dissolved oxygen improvement.

A novel aerator for enhancing the oxygen transfer rate and efficiency, named multistage vortex aerator (MVA), was developed. It uses vortex flow in repeated stages to increase the gas-liquid interfacial area and to decrease the thickness of the stagnant layer at the interface between the two phases. The basic characteristics of oxygen transfer using this aerator were investigated using the American Society of Civil Engineers standard procedure. The MVA could rapidly transfer oxygen to water to a concentration higher than 40 mg/L in 60 min owing to the effect of high purity oxygen, additional pressure induced by water and gas, and vortex flow dynamics. A gas transfer model was developed for describing the non-steady state operation of the aerator. This model is based on the mass and molar balances of oxygen in gas and water. It could successfully simulate the DO change inside the aerator. This study can help better understand the oxygen transfer mechanism and evaluate the performance of the new aerator at the various temperatures, pressures, and gas compositions found in diverse environmental systems.

Nonvolatile Control of Metal-Insulator Transition in VO2 by Ferroelectric Gating.

Controlling phase transitions in correlated materials yields emergent functional properties, providing new aspects to future electronics and a fundamental understanding of condensed matter systems. With vanadium dioxide (VO2 ), a representative correlated material, an approach to control a metal-insulator transition (MIT) behavior is developed by employing a heteroepitaxial structure with a ferroelectric BiFeO3 (BFO) layer to modulate the interaction of correlated electrons. Owing to the defect-alleviated interfaces, the enhanced coupling between the correlated electrons and ferroelectric polarization is successfully demonstrated by showing a nonvolatile control of MIT of VO2 at room temperature. The ferroelectrically-tunable MIT can be realized through the Mott transistor (VO2 /BFO/SrRuO3 ) with a remanent polarization of 80 µC cm-2 , leading to a nonvolatile MIT behavior through the reversible electrical conductance with a large on/off ratio (≈102 ), long retention time (≈104 s), and high endurance (≈103 cycles). Furthermore, the structural phase transition of VO2 is corroborated by ferroelectric polarization through in situ Raman mapping analysis. This study provides novel design principles for heteroepitaxial correlated materials and innovative insight to modulate multifunctional properties.

High performance inkjet printed embedded electrochemical sensors for monitoring hypoxia in a gut bilayer microfluidic chip.

Sensing devices have shown tremendous potential for monitoring state-of-the-art organ chip devices. However, challenges like miniaturization while maintaining higher performance, longer operating times for continuous monitoring, and fabrication complexities limit their use. Herein simple, low-cost, and solution-processible inkjet dispenser printing of embedded electrochemical sensors for dissolved oxygen (DO) and reactive oxygen species (ROS) is proposed for monitoring developmental (initially normoxia) and induced hypoxia in a custom-developed gut bilayer microfluidic chip platform for 6 days. The DO sensors showed a high sensitivity of 31.1 nA L mg-1 with a limit of detection (LOD) of 0.67 mg L-1 within the 0-9 mg L-1 range, whereas the ROS sensor had a higher sensitivity of 1.44 nA µm-1 with a limit of detection of 1.7 µm within the 0-300 µm range. The dynamics of the barrier tight junctions are quantified with the help of an in-house developed trans-epithelial-endothelial electrical impedance (TEEI) sensor. Immunofluorescence staining was used to evaluate the expressions of HIF-1α and tight junction protein (TJP) ZO-1. This platform can also be used to enhance bioavailability assays, drug transport studies under an oxygen-controlled environment, and even other barrier organ models, as well as for various applications like toxicity testing, disease modeling and drug screening.

Laboratory and field study on changes in water quality and increase in dissolved iron during riverbank filtration.

Changes in the water quality by the riverbank filtration (RBF) process were investigated in the field-scale demonstration sites. The overall water quality was improved by RBF, but Fe2+ concentration significantly increased in the riverbank-filtered water more than in the river water. This result would be caused by the interaction between the iron minerals and the river water in the aquifer and the influx of the hinterland groundwater into RBF wells. Dissolution properties of iron from the aquifer soils cored at the sites were evaluated through incubation experiment considering various values of redox potential (Eh), dissolved oxygen (DO), and hydrogen-ion concentration exponent (pH). These results presented that at the incubator with the final Eh of 470 mV, DO of 3.4, and pH of 4.53, the iron from the aquifer soil was most dissolved, and the pyrite and siderite contents in the aquifer soil decreased significantly from 11.5 to 6.22% and from 50.8 to 24.5%, respectively. Based on changes of ion concentrations (such as Fe2+, Fe3+, SO42- and NO3-) and iron species in the incubators, it was believed that pyrite and siderite minerals in the aquifer soils cause an increase in the Fe2+ concentration with the absence of DO and an increase in the Fe2+ and Fe3+ concentrations with the presence of DO. The dissolution rates of iron minerals into Fe2+ and Fe3+ were dependent on Eh, pH, and DO and were more sensitive to Eh and pH than DO. The results of this study can provide information on RBF site selection and its operation.

Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system.

Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor ß1 (TGF-ß1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-ß1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

Reduced graphene oxide-mediated Z-scheme BiVO4/CdS nanocomposites for boosted photocatalytic decomposition of harmful organic pollutants.

The efficient photocatalytic degradation of harmful organic pollutants (isoniazid (ISN) and 1,4-dioxane (DX)) via the Z-scheme electron transfer mechanism was accomplished using a photostable composite photocatalyst consisting of BiVO4, CdS, and reduced graphene oxide (RGO). Compared to their pristine counterparts, the RGO-mediated Z-scheme CdS/BiVO4 (CdS/RGO-BiVO4) nanocomposites exhibited superior degradation activities, mainly attributed to the prolonged charge separation. RGO was found to be involved in visible-light harvesting and acted as a solid-state electron mediator at the CdS/BiVO4 interface to realize an effective Z-scheme electron transfer pathway, avoid photocatalyst self-oxidation, and lengthen the life span of charge carriers. The results of reactive species scavenging experiments, photoluminescence measurements, and transient photocurrent measurements, as well as the calculated band potentials of the synthesized photocatalysts, supported the Z-scheme electron/hole pair separation mechanism. Additionally, the intermediates formed during the degradation of ISN and DX were identified, and a possible fragmentation pattern was proposed. This systematic work aims to develop photostable Z-scheme composites as unique photocatalytic systems for the efficient removal of harmful organic pollutants.

Modeling full-scale osmotic membrane bioreactor systems with high sludge retention and low salt concentration factor for wastewater reclamation.

A full-scale model was developed to find optimal design parameters for osmotic membrane bioreactor (OMBR) and reverse osmosis (RO) hybrid system for wastewater reclamation. The model simulates salt accumulation, draw solution dilution and water flux in OMBR with sludge concentrator for high retention and low salt concentration factor. The full-scale OMBR simulation results reveal that flat-sheet module with spacers exhibits slightly higher flux than hollow-fiber; forward osmosis (FO) membrane with high water permeability, low salt permeability, and low resistance to salt diffusion shows high water flux; an optimal water recovery around 50% ensures high flux and no adverse effect on microbial activity; and FO membrane cost decreases and RO energy consumption and product water concentration increases at higher DS flow rates and concentrations. The simulated FO water flux and RO energy consumption ranges from 3.03 to 13.76LMH and 0.35 to 1.39kWh/m(3), respectively.

Neuroprotective effect of 6-paradol in focal cerebral ischemia involves the attenuation of neuroinflammatory responses in activated microglia.

Paradols are non-pungent and biotransformed metabolites of shogaols and reduce inflammatory responses as well as oxidative stress as shogaols. Recently, shogaol has been noted to possess therapeutic potential against several central nervous system (CNS) disorders, including cerebral ischemia, by reducing neuroinflammation in microglia. Therefore, paradol could be used to improve neuroinflammation-associated CNS disorders. Here, we synthesized paradol derivatives (2- to 10-paradols). Through the initial screening for anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated BV2 microglia, 6-paradol was chosen to be the most effective compound without cytotoxicity. Pretreatment with 6-paradol reduced neuroinflammatory responses in LPS-stimulated BV2 microglia by a concentration-dependent manner, which includes reduced NO production by inhibiting iNOS upregulation and lowered secretion of proinflammatory cytokines (IL-6 and TNF-α). To pursue whether the beneficial in vitro effects of 6-paradol leads towards in vivo therapeutic effects on transient focal cerebral ischemia characterized by neuroinflammation, we employed middle cerebral artery occlusion (MCAO)/reperfusion (M/R). Administration of 6-paradol immediately after reperfusion significantly reduced brain damage in M/R-challenged mice as assessed by brain infarction, neurological deficit, and neural cell survival and death. Furthermore, as observed in cultured microglia, 6-paradol administration markedly reduced neuroinflammation in M/R-challenged brains by attenuating microglial activation and reducing the number of cells expressing iNOS and TNF-α, both of which are known to be produced in microglia following M/R challenge. Collectively, this study provides evidences that 6-paradol effectively protects brain after cerebral ischemia, likely by attenuating neuroinflammation in microglia, suggesting it as a potential therapeutic agent to treat cerebral ischemia.