SST: a snore shifted-window transformer method for potential obstructive sleep apnea patient diagnosis.

Objective.Obstructive sleep apnea (OSA) is a high-incidence disease that is seriously harmful and potentially dangerous. The objective of this study was to develop a noncontact sleep audio signal-based method for diagnosing potential OSA patients, aiming to provide a more convenient diagnostic approach compared to the traditional polysomnography (PSG) testing.Approach.The study employed a shifted window transformer model to detect snoring audio signals from whole-night sleep audio. First, a snoring detection model was trained on large-scale audio datasets. Subsequently, the deep feature statistical metrics of the detected snore audio were used to train a random forest classifier for OSA patient diagnosis.Main results.Using a self-collected dataset of 305 potential OSA patients, the proposed snore shifted-window transformer method (SST) achieved an accuracy of 85.9%, a sensitivity of 85.3%, and a precision of 85.6% in OSA patient classification. These values surpassed the state-of-the-art method by 9.7%, 10.7%, and 7.9%, respectively.Significance.The experimental results demonstrated that SST significantly improved the noncontact audio-based OSA diagnosis performance. The study's findings suggest a promising self-diagnosis method for potential OSA patients, potentially reducing the need for invasive and inconvenient diagnostic procedures.

Modification of Pillared Intercalated Montmorillonite Clay as Heterogeneous Pd Catalyst Supports.

Montmorillonite clay was modified by pillaring with AlMn oxides in different Al/Mn ratios and intercalation of two kinds of N-containing polymers (i.e., chitosan (CS) and polyvinyl pyrrolidinone (PVP)) chains. The modified pillared montmorillonite clay (PM) showed a rich two-dimensional layered porous structure with tunable parameters, such as large interlayer spacing, high specific area, and large porous volume. They were then used as supports for Pd nanoparticles. As applied in coupling reactions of aryl halides with terminal alkynes, Pd@CS/AlMn-PM showed better comprehensive catalytic performance than Pd@PVP/AlMn-PM. This was mainly attributed to its higher specific area, stronger chelation to Pd species, and better solvent resistance.

TiO2-Modified Montmorillonite-Supported Porous Carbon-Immobilized Pd Species Nanocomposite as an Efficient Catalyst for Sonogashira Reactions.

In this study, a combination of the porous carbon (PCN), montmorillonite (MMT), and TiO2 was synthesized into a composite immobilized Pd metal catalyst (TiO2-MMT/PCN@Pd) with effective synergism improvements in catalytic performance. The successful TiO2-pillaring modification for MMT, derivation of carbon from the biopolymer of chitosan, and immobilization of Pd species for the prepared TiO2-MMT/PCN@Pd0 nanocomposites were confirmed using a combined characterization with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N2 adsorption-desorption isotherms, high-resolution transition electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. It was shown that the combination of PCN, MMT, and TiO2 as a composite support for the stabilization of the Pd catalysts could synergistically improve the adsorption and catalytic properties. The resultant TiO2-MMT80/PCN20@Pd0 showed a high surface area of 108.9 m2/g. Furthermore, it exhibited moderate to excellent activity (59-99% yield) and high stability (recyclable 19 times) in the liquid-solid catalytic reactions, such as the Sonogashira reactions of aryl halides (I, Br) with terminal alkynes in organic solutions. The positron annihilation lifetime spectroscopy (PALS) characterization sensitively detected the development of sub-nanoscale microdefects in the catalyst after long-term recycling service. This study provided direct evidence for the formation of some larger-sized microdefects during sequential recycling, which would act as leaching channels for loaded molecules, including active Pd species.

Inhibition of cGAS in Paraventricular Nucleus Attenuates Hypertensive Heart Injury Via Regulating Microglial Autophagy.

Neuroinflammation in the cardiovascular center plays a critical role in the progression of hypertensive heart disease. And microglial autophagy is involved in the regulation of neuroinflammation. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, senses mitochondrial DNA (mtDNA) and regulates autophagy. The detailed mechanisms of central cGAS affects neuroinflammatory response in hypertensive heart disease via regulating autophagy remain unknown. Angiotensin II (Ang II, 1.5 mg·kg-1·12 h-1, 2 weeks) was intraperitoneally injected to induce hypertension in mice. The cGAS-STING pathway was activated in the paraventricular nucleus (PVN) of Ang II-induced hypertensive mice. The contractile dysfunction of heart was alleviated in Ang II-induced hypertensive cGAS-/- mice. To observe the central effects of cGAS on regulating hypertensive heart disease, the RU.521 (a cGAS inhibitor) was intracisternally infused in hypertensive mice. Intracisternal infusion of the RU.521-alleviated myocardial interstitial fibrosis, cardiomyocyte hypertrophy, and the contractile dysfunction in Ang II-induced hypertensive mice. Intracisternal infusion of RU.521 attenuated the microglial activation, neuroinflammation, sympathetic/parasympathetic activity ratio, and lowered blood pressure. The autophagic flux in the PVN cells was blocked, while intracisternal infusion of RU.521 alleviated this effect in the Ang II-induced hypertensive mice. In vitro, it was found that cGAS-STING activation-induced autophagic flux blockage, while when the impaired autophagic flux was facilitated by rapamycin, an autophagy inducer, the microglial M1 polarization was decreased correspondingly. In conclusion, cGAS induces the inflammatory phenotype of microglia via impairing autophagic flux, thereby participating in neuroinflammation, which leads to sympathetic overactivation in hypertension and further caused hypertensive myocardial injury.

Inhibition of the cGAS-STING Pathway Attenuates Lung Ischemia/Reperfusion Injury via Regulating Endoplasmic Reticulum Stress in Alveolar Epithelial Type II Cells of Rats.

Purpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS. Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system. Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats. Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.

PLIN2 Mediates Neuroinflammation and Oxidative/Nitrosative Stress via Downregulating Phosphatidylethanolamine in the Rostral Ventrolateral Medulla of Stressed Hypertensive Rats.

PURPOSE: Oxidative/nitrosative stress, neuroinflammation and their intimate interactions mediate sympathetic overactivation in hypertension. An immoderate inflammatory response is characterized not only by elevated proinflammatory cytokines (PICs) but by increases in mitochondrial dysfunction, reactive oxygen species (ROS), and nitric oxide (NO). Recent data pinpoint that both the phospholipid and lipid droplets (LDs) are potent modulators of microglia physiology. METHODS: Stress rats underwent compound stressors for 15 days with PLIN2-siRNA or scrambled-siRNA (SC-siRNA) administrated into the rostral ventrolateral medulla (RVLM). Lipids were analyzed by mass spectroscopy-based quantitative lipidomics. The phenotypes and proliferation of microglia, LDs, in the RVLM of rats were detected; blood pressure (BP) and myocardial injury in rats were evaluated. The anti-oxidative/nitrosative stress effect of phosphatidylethanolamine (PE) was explored in cultured primary microglia. RESULTS: Lipidomics analysis showed that 75 individual lipids in RVLM were significantly dysregulated by stress [PE was the most one], demonstrating that lipid composition changed with stress. In vitro, prorenin stress induced the accumulation of LDs, increased PICs, which could be blocked by siRNA-PLIN2 in microglia. PLIN2 knockdown upregulated the PE synthesis in microglia. Anti-oxidative/nitrosative stress effect of PE delivery was confirmed by the decrease of ROS and decrease in 3-NT and MDA in prorenin-treated microglia. PLIN2 knockdown in the RVLM blocked the number of iNOS+ and PCNA+ microglia, decreased BP, alleviated cardiac fibrosis and hypertrophy in stressed rats. CONCLUSION: PLIN2 mediates microglial polarization/proliferation via downregulating PE in the RVLM of stressed rats. Delivery of PE is a promising strategy for combating neuroinflammation and oxidative/nitrosative stress in stress-induced hypertension.

Design of Metasurface with Nanoslits on Elliptical Curves for Generation of Dual-Channel Vector Beams.

The manipulations of nanoscale multi-channel vector beams (VBs) by metasurfaces hold potential applications in various important fields. In this paper, the metasurface with two sets of nanoslits arranged on elliptic curves was proposed to generate the dual-channel focused vector beams (FVBs). Each set of nanoslits was composed of the in-phase and the out-of-phase groups of nanoslits to introduce the constructive interference and destructive interference of the output light field of the nanoslits, focusing the converted spin component and eliminating the incident spin component at the focal point. The two sets of nanoslits for the channels at the two focal points were interleaved on the same ellipses, and by setting their parameters independently, the FVBs in the two channels are generated under illumination of linearly polarized light, while their orders and polarization states of FVBs were controlled independently. The generation of the FVBs with the designed metasurfaces was demonstrated by the finite-difference time domain (FDTD) simulations and by the experimental verifications. The work in this paper is of great significance for the generation of miniaturized multi-channel VBs and for broadening the applications of metasurfaces.

Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum-Mitochondria Contact and Mitochondrial Functions in Stress-Induced Hypertension Rats.

Exposure to stress plays a detrimental role in the pathogenesis of hypertension via neuroinflammation pathways. Microglial neuroinflammation in the rostral ventrolateral medulla (RVLM) exacerbates stress-induced hypertension (SIH) by increasing sympathetic hyperactivity. Mitochondria of microglia are the regulators of innate immune response. Sigma-1R (σ-1R) localizes to the mitochondria-associated membranes (MAMs) and regulates endoplasmic reticulum (ER) and mitochondria communication, in part through its chaperone activity. The present study aims to investigate the protective role of σ-1R on microglial-mediated neuroinflammation. Stress-induced hypertension (SIH) was induced in rats using electric foot shocks and intermittent noise. Arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to evaluate the sympathetic nervous system (SNS) activities. SKF10047 (100 µM), an agonist of σ-1R, was administrated to rats, then σ-1R localization and MAM alterations were detected by immuno-electron microscopy. Mitochondrial calcium homeostasis was examined in primary microglia and/or BV-2 microglia cells. The effect of SKF10047 treatment on the mitochondrial respiratory function of cultured microglia was measured using a Seahorse Extracellular Flux Analyzer. Confocal microscopic images were performed to indicate mitochondrial dynamics. Stress reduces σ-1R's localization at the MAMs, leading to decreased ER-mitochondria contact and IP3R-GRP75-VDAC calcium transport complexes expression in the RVLM of rats. SKF10047 promotes the length and coverage of MAMs in the prorenin-treated microglia. Prorenin treatment increases mitoROS levels, and inhibits Ca2+ signalling between the two organelles, therefore negatively affects ATP production in BV2 cells, and these effects are reversed by SKF10047 treatment. We found mitochondrial hyperfusion and microglial M1 polarization in prorenin-treated microglia. SKF10047 suppresses microglial M1 polarization and RVLM neuroinflammation, subsequently ameliorates sympathetic hyperactivity in stress-induced hypertensive rats. Sigma-1 receptor activation suppresses microglia M1 polarization and neuroinflammation via regulating endoplasmic reticulum-mitochondria contact and mitochondrial functions in stress-induced hypertension rats.

Inhibition of MALT1 Alleviates Spinal Ischemia/Reperfusion Injury-Induced Neuroinflammation by Modulating Glial Endoplasmic Reticulum Stress in Rats.

PURPOSE: Glial activation and the disorders of cytokine secretion induced by endoplasmic reticulum stress (ERS) are crucial pathogenic processes in establishing ischemia/reperfusion (I/R) injury of the brain and spinal cord. This present study aimed to investigate the effects of mucous-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) on spinal cord ischemia/reperfusion (SCI/R) injury via regulating glial ERS. METHODS: SCI/R was induced by thoracic aorta occlusion-reperfusion in rats. The MALT1-specific inhibitor MI-2 or human recombinant MALT1 protein (hrMALT1) was administrated for three consecutive days after the surgery. Immunofluorescent staining was used to detect the localization of MALT1 and ERS profiles in activated astrocyte and microglia of spinal cord. The ultrastructure of endoplasmic reticulum (ER) was examined by transmission electron microscopy. Blood-spinal cord barrier (BSCB) disruption and noninflammatory status were assessed. The neuron loss and demyelination in the spinal cord were monitored, and the hindlimb motor function was evaluated in SCI/R rats. RESULTS: Intraperitoneally postoperative MI-2 treatment down-regulated phos-NF-κB (p65) and Bip (ERS marker protein) expression in the spinal cord after SCI/R in rats. Intraperitoneal injection MI-2 attenuated the swelling/dilation of ER of the glia in SCI/R rats. Furthermore, MI-2 attenuated I/R-induced Evans blue (EB) leakage and microglia M1 polarization in spinal cord, implying a role for MALT1 in the BSCB destruction and neuroinflammation after SCI/R in rats. Furthermore, intrathecal injection of hrMALT1 aggravated the fragmentation of neuron, loss of neurofibrils and demyelination caused by I/R, while 4-PBA, an ERS inhibitor, co-treatment with hrMALT1 reversed these effects in SCI/R rats. hrMALT1 administration aggravated the motor deficit index (MDI) scoring, while 4-PBA co-treatment improved SCI/R-induced motor deficits in rats. CONCLUSION: Inhibition of MALT1 alleviates SCI/R injury-induced neuroinflammation by modulating glial endoplasmic reticulum stress in rats.

Optical Spin Hall Effect in Closed Elliptical Plasmonic Nanoslit with Noncircular Symmetry.

We investigated the optical spin Hall effect (OSHE) of the light field from a closed elliptical metallic curvilinear nanoslit instead of the usual truncated curvilinear nanoslit. By making use of the characteristic bright spots in the light field formed by the noncircular symmetry of the elliptical slit and by introducing a method to separate the incident spin component (ISC) and converted spin component (CSC) of the output field, the OSHE manifested in the spot shifts in the CSC was more clearly observable and easily measurable. The slope of the elliptical slit, which was inverse along the principal axes, provided a geometric phase gradient to yield the opposite shifts of the characteristic spots in centrosymmetry, with a double shift achieved between the spots. Regarding the mechanism of this phenomenon, the flip of the spin angular momentum (SAM) of CSC gave rise to an extrinsic orbital angular momentum corresponding to the shifts of the wavelet profiles of slit elements in the same rotational direction to satisfy the conservation law. The analytical calculation and simulation of finite-difference time domain were performed for both the slit element and the whole slit ellipse, and the evolutions of the spot shifts as well as the underlying OSHE with the parameters of the ellipse were achieved. Experimental demonstrations were conducted and had consistent results. This study could be of great significance for subjects related to the applications of the OSHE.

Generation of vector beams of Bell-like states by manipulating vector vortex modes with plasmonic metasurfaces.

Metasurfaces with orthogonal nano-slit pairs arranged on spirals are proposed to generate vector beams (VBs) of Bell-like states and slanted polarizations. The design of the metasurfaces is based on the theoretically derived parameter condition for manipulation of the two vector vortex modes, which is satisfied by matching the three parameters of rotation order m, the spiral order n, and incident polarization helicity σ. The linear polarization states of the VBs are controlled by the initial orientation angle φ0 of slit pairs. VBs of satisfying quality are experimentally obtained, with the analytical and simulated results validated.

Flexible generation of higher-order Poincaré beams with high efficiency by manipulating the two eigenstates of polarized optical vortices.

Vector beams contain complex polarization structures and they are inherently non-separable in the polarization and spatial degrees of freedom. The spatially variant polarizations of vector beams have enabled many important applications in a variety of fields ranging from classical to quantum physics. In this study, we designed and realized a setup based on Mach-Zehnder interferometer for achieving the vector beams at arbitrary points of higher-order Poincaré sphere, through manipulating two eigenstates in the Mach-Zehnder interferometer system with the combined spiral phase plate. We demonstrated the generation of different kinds of higher-order Poincaré beams, including the beams at points on a latitude or longitude of higher-order Poincaré sphere, Bell states for |l| = 1 and |l| = 2, radially polarized beams of very high order with l = 16, etc. Vector beams of high quality and good accuracy are experimentally achieved, and the flexibility, feasibility and high efficiency of the setup are demonstrated by the practical performance.

A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells.

Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (H2O2)-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the H2O2-mediated conversion of boronate to free phenol. The boronate-protected Nap (PNap) can exploit increased levels of H2O2 in HepG2 cells to in situ release Nap followed by its efflux via conjugation with reduced glutathione (GSH), allowing that the Nap-GSH adduct works as a Cu(II) ionophore to induce continuously GSH depletion via a reduction-dependent releasing of Cu(I) by GSH. This strategy endows PNap with the unprecedented ability to hit multi-redox characteristics (increased levels of H2O2, GSH and copper) of HepG2 cells, leading to ROS generation preferentially in HepG2 cells along with their selective death.

Nanoscale optical lattices of arbitrary orders manipulated by plasmonic metasurfaces combining geometrical and dynamic phases.

Metasurfaces can be used to manipulate light at the subwavelength scale, and miniaturized photonic devices can be designed to generate subwavelength lattices, which are important for exploring phenomena in novel fields of physics such as topology. Analogous to multi-beam interference, plasmonic metasurfaces composed of nano-slit pairs on truncated spiral segments were designed and fabricated to realize lattice wave fields at a subwavelength resolution. The interference of the analogous beams was controlled by combining the geometric and dynamic phases, and lattices of different morphologies were realized by adjusting the orientation and position of the nano-slits simultaneously. The numerical and measured results showed good agreement, demonstrating the feasibility of the method and its ability to miniaturize lattice patterns. Owing to the compactness and flexible tunability, the nanoscale optical lattices generated using the metasurfaces are expected to find wide applications in integrated and on-chip optical systems.

Facile, eco-friendly, catalyst-free synthesis of polyfunctionalized quinoxalines.

A novel, facile and eco-friendly synthesis of quinoxalines from [Formula: see text] and 1,2-diamines was developed. An attractive feature of this protocol is that the desired products could be generated efficiently in water and without any catalyst, which is in accordance with the aim of green chemistry. A plausible mechanism has been proposed.

A novel quinazoline-based analog induces G2/M cell cycle arrest and apoptosis in human A549 lung cancer cells via a ROS-dependent mechanism.

6-amino-4-(4-phenoxyphenylethylamino)quinazoline (QNZ) is an excellent quinazoline-containing NF-κB inhibitor also acting as a novel anticancer agent. Considering both the medicinal significance of quinazoline scaffold and the tunable functionality of Michael acceptor-centric pharmacophores in the electrophilicity-based prooxidant strategy, we designed a novel QNZ-inspired electrophilic molecule QNZ-A by introducing a Michael acceptor unit at position-6 of quinazoline ring in QNZ. Our results identified QNZ-A as a promising selective cytotoxic agent against A549 cells. QNZ-A, by virtue of its Michael acceptor unit, induced reactive oxygen species (ROS) accumulation associated with collapse of the redox buffering system in A549 cells. This caused up-regulation of p53-inducible p21 and down-regulation of redox sensitive Cdc25C along with Cyclin B1/Cdk1, leading to a G2/M cell cycle arrest and final cell apoptosis. By contrast, QNZ-B, a reduction product of QNZ-A lacking the Michael acceptor unit failed to induce ROS generation and all these cell cycle-related events. In conclusion, this work provided a successful example of designing QNZ-directed anticancer agent by a ROS-promoting strategy and identified QNZ-A as a selective anticancer agent against A549 cells through G2/M cell cycle arrest and apoptosis via a ROS-dependent mechanism.

Mechanistic Study on Gold-Catalyzed Highly Selective Hydroamination of Alkylidenecyclopropanes.

Density functional theory calculations have been carried out to study the mechanism of the gold-catalyzed highly selective hydroamination of alkylidenecyclopropanes. Two main mechanisms (i.e., double-bond activation-first and three-membered-ring activation-first mechanisms) have been examined. The double-bond activation-first mechanism results in the alkene hydroamination product, and it mainly consists of three steps: C-N bond formation, C-C bond rotation, and protodeauration (rate-determining step). Meanwhile, the three-membered-ring activation-first mechanism finally produces allylic amines, and it occurs via the ring-opening (rate-determining step), C-N bond formation, and protodeauration steps. The calculation results show good agreement with the experimental outcomes on the chemo-, regio-, and diastereoselectivity. On this basis, we found that the regioselectivity is caused by the C-C bond rotation step, while the diastereoselectivity is determined by both the C-C bond rotation and the protodeauration steps in the double-bond activation-first mechanism.

Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds.

[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates. Noticeably, existence of the 5-OH decreases their formal hydrogen-transfer and electron-donating abilities, but increases their DNA damage- and lipid peroxidation-protecting abilities. Additionally, despite significantly reducing their DNA strand breakage-inhibiting activity, extension of the chain length from six to twelve carbons enhances their anti-haemolysis activity.

Tailoring 3,3'-dihydroxyisorenieratene to hydroxystilbene: finding a resveratrol analogue with increased antiproliferation activity and cell selectivity.

Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol-inspired antiproliferative agents.

An effective strategy to develop active cinnamic acid-directed antioxidants based on elongating the conjugated chains.

To optimize antioxidant activity and lipophilicity of cinnamic acid derivatives (CAs) including ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, and p-hydroxycinnamic acid, four analogs bearing an additional double bond between their aromatic ring and propenoic acid moiety were designed and synthesized based on the conjugated chain elongation strategy. The antioxidant performance of the CAs were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH)-scavenging, ferric reducing/antioxidant power, cyclic voltammetry, DNA strand breakage-inhibiting and anti-haemolysis activity assays. It was found that CAs with elongation of conjugated chains display increased DPPH-scavenging, DNA strand breakage-inhibiting and anti-haemolysis activities as compared to their parent molecules, due to their improved hydrogen atom-donating ability and lipophilicity. Overall, this work highlights an effective strategy to develop potential CA-directed antioxidants by elongating their conjugated chain.