CELA-MFP: a contrast-enhanced and label-adaptive framework for multi-functional therapeutic peptides prediction.

Functional peptides play crucial roles in various biological processes and hold significant potential in many fields such as drug discovery and biotechnology. Accurately predicting the functions of peptides is essential for understanding their diverse effects and designing peptide-based therapeutics. Here, we propose CELA-MFP, a deep learning framework that incorporates feature Contrastive Enhancement and Label Adaptation for predicting Multi-Functional therapeutic Peptides. CELA-MFP utilizes a protein language model (pLM) to extract features from peptide sequences, which are then fed into a Transformer decoder for function prediction, effectively modeling correlations between different functions. To enhance the representation of each peptide sequence, contrastive learning is employed during training. Experimental results demonstrate that CELA-MFP outperforms state-of-the-art methods on most evaluation metrics for two widely used datasets, MFBP and MFTP. The interpretability of CELA-MFP is demonstrated by visualizing attention patterns in pLM and Transformer decoder. Finally, a user-friendly online server for predicting multi-functional peptides is established as the implementation of the proposed CELA-MFP and can be freely accessed at http://dreamai.cmii.online/CELA-MFP.

A Homogeneous Janus Membrane Based on Functionalized MOFs Crosslinked by Aramid Nanofibers for Quasi-Solid-State Lithium Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are considered as promising candidates in the next generation of high energy density devices. However, the serious shuttle effect, irreversible dendrite growth of Li metal anode, and the potential safety hazard impede the practical application of LSBs. Herein, a novel homogeneous Janus membrane based on functionalized MOFs crosslinked by aramid nanofibers is designed and synthesized to simultaneously solve the above challenges in quasi-solid-state LSBs. The aramid nanofibers with good mechanical properties and thermal stability act as a homogeneous scaffold to crosslink the MOF particles with different ligands on both sides and this Janus membrane upgrades the stability and safety on both the cathode and anode. Specifically, the amino ligand-decorated MOFs contribute to homogenize Li-ion flux and stabilize the lithium anode, and the sulfonic ligand-decorated MOFs effectively suppress the shuttle effect by the dual effects of chemical adsorption and electrostatic repulsion. The quasi-solid-state LSBs assembled with this homogeneous Janus membrane deliver excellent rate performance and cycling stability. Moreover, it exhibits a high initial capacity of 923.4 mAh g-1 at 1 C at 70 °C, and 697.3 mAh g-1 is retained after 100 cycles, indicating great potential for its application in high-safety LSBs.

Excellent Room Temperature Thermoelectric Performance in Mg3Sb2-Based Alloys via Multi-Functional Doping of Nb.

Mg3Sb2-based alloys are attracting increasing attention due to the excellent room temperature thermoelectric properties. However, due to the presence and easy segregation of charged Mg vacancies, the carrier mobility in Mg3Sb2-based alloys is always severely compromised that significantly restricts the room temperature performance. General vacancy compensation strategies cannot synergistically optimize the complicated Mg3Sb2 structures involving both interior and boundary scattering. Herein, due to the multi-functional doping effect of Nb, the electron scattering inside and across grains is significantly suppressed by inhibiting the accumulation of Mg vacancies, and leading to a smooth transmission channel of electrons. The increased Mg vacancies migration barrier and optimized interface potential are also confirmed theoretically and experimentally, respectively. As a result, a leading room temperature zT of 1.02 is achieved. This work reveals the multi-functional doping effect as an efficient approach in improving room temperature thermoelectric performance in complicated defect/interface associated Mg3Sb2-based alloys.

MMDB: Multimodal dual-branch model for multi-functional bioactive peptide prediction.

Bioactive peptides can hinder oxidative processes and microbial spoilage in foodstuffs and play important roles in treating diverse diseases and disorders. While most of the methods focus on single-functional bioactive peptides and have obtained promising prediction performance, it is still a significant challenge to accurately detect complex and diverse functions simultaneously with the quick increase of multi-functional bioactive peptides. In contrast to previous research on multi-functional bioactive peptide prediction based solely on sequence, we propose a novel multimodal dual-branch (MMDB) lightweight deep learning model that designs two different branches to effectively capture the complementary information of peptide sequence and structural properties. Specifically, a multi-scale dilated convolution with Bi-LSTM branch is presented to effectively model the different scales sequence properties of peptides while a multi-layer convolution branch is proposed to capture structural information. To the best of our knowledge, this is the first effective extraction of peptide sequence features using multi-scale dilated convolution without parameter increase. Multimodal features from both branches are integrated via a fully connected layer for multi-label classification. Compared to state-of-the-art methods, our MMDB model exhibits competitive results across metrics, with a 9.1% Coverage increase and 5.3% and 3.5% improvements in Precision and Accuracy, respectively.

Chiral pyrrolidines as multipotent agents in Alzheimer and neurodegenerative diseases.

In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.

The Investigation of the Effect of La3+, Eu3+, and Sm3+ Ions on Photoluminescence and Piezoelectric Behavior of RE1.90Y0.10Zr2O7 (RE: Eu, Sm and Y: La, Sm, Eu) Pyrochlore-Based Multifunctional Smart Advanced Materials.

A series of compounds with the general formula RE1.90Y0.10Zr2O7 (where RE includes Eu, Sm and Y includes La, Sm, Eu) were synthesized using a solid-state reaction method. These compounds were analyzed through differential thermal analysis (DTA), thermogravimetric analysis (TG), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). Additionally, their dielectric constant, loss tangent, piezoelectric charge constant, and Curie temperature were measured using an LCR meter, d33 meter, and TG/DTA. X-ray diffraction results indicated that all samples crystallize in a cubic pyrochlore structure. Photoluminescence studies revealed that Eu3+ ions predominantly contribute to the emission, whether as activators or co-activators. Among the phosphors, Eu1.90La0.10Zr2O7 exhibited a significantly longer afterglow compared to Sm1.90Eu0.10Zr2O7 and Eu1.90Sm0.10Zr2O7. Conversely, Sm1.90Eu0.10Zr2O7 demonstrated luminescence intensity that was 20 times greater than that of Eu1.90La0.10Zr2O7 and Eu1.90Sm0.10Zr2O7. Furthermore, all samples with characteristic Eu3+ emissions also exhibited piezoelectric properties. Curie temperature (Tc) of Eu1.90La0.10Zr2O7, Sm1.90Eu0.10Zr2O7, and Eu1.90Sm0.10Zr2O7 are 770°C, 830°C, and 845°C, respectively. Therefore, Sm3+ ion improves piezoelectric properties and Curie temperature when doping into the Eu2Zr2O7 host crystal.

Evaluation of GHK peptide-heparin interactions in multifunctional liposomal covering.

Small biospecific peptides with defined chemical structure and cellular responses are promising alternatives to full-length therapeutic proteins. Identification of these peptides solely or in combination with other bioactive factors and determination of their targets are of substantial interest in current drug delivery research. This study is aimed at the development of new liposomal formulations of ECM-derived GHK peptide known for its multiple regeneration-related activities but poorly recognized cellular targets. In situ association of membranotropic GHK derivative with unilamellar liposomes was performed to prepare GHK-modified liposomes with defined properties. According to DLS, the GHK component on the liposomal surface interacted with heparin in a specific manner compared to other polysaccharides and RGD counterpart, whereas ITC analysis of such interactions was complicated. The results provide a useful tool for screening of bio-interactions of synthetic peptide-presenting liposomes by the DLS technique. They were also employed to produce a multi-functional nanosized GHK-heparin covering for liposomes. The resulting composite liposomes possessed low size dispersity, increased anionic charge, and mechanical rigidity. The heparin component significantly promoted the accumulation of GHK-modified liposomes in 3T3 fibroblasts so that the composite liposomes exhibited the highest cell-penetrating activity. Furthermore, the latter formulation stimulated cell proliferation and strongly inhibited ROS production and GSH depletion under oxidative stress conditions. Together, the results support that cell-surface glycosaminoglycans can be involved in GHK-mediated liposomal delivery, which can be further greatly enhanced by association with heparin. The composite liposomes with GHK-heparin covering can be considered as an advanced GHK-based formulation for therapeutic and cosmeceutical applications.

Metamaterial Inspired Varactor-Tuned Antenna with Frequency Reconfigurability and Pattern Diversity.

A metamaterial-inspired varactor-tuned antenna with frequency reconfigurability and pattern diversity is designed. Two different versions of a reconfigurable structure are integrated into a single antenna to excite two different orthogonal patterns, which realizes pattern diversity for MIMO applications. The outer annular Composite Right-/Left-Handed Transmission Line (CRLH-TL) works at the 1 mode and provides a broadside pattern, and the inner circular radiator loaded with split ring resonators (SRR) operates at the 0 mode and radiates an omnidirectional pattern, which realizes pattern diversity. By using surface-mounted varactors, the operating frequencies for the two radiation patterns can be tuned over a wide frequency range, from 1.7 GHz to 2.2 GHz, covering the 1.71-2.17 GHz LTE band, and a low mutual coupling between the two radiators is achieved. The antenna has also been prototyped. The measured results are in good agreement with the simulation results, verifying the proposed concept. The dual-mode MIMO system equipped with the proposed antenna elements is discussed within the context of a 3-D channel model, and it shows a superior array compactness and spectral efficiency (SE) performance compared to scenarios with single-mode elements.

Multi-Functional Formaldehyde-Nitrate Batteries for Wastewater Refining, Electricity Generation, and Production of Ammonia and Formate.

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

CoFe2O4@SiO2-NH2@MOF-5 magnetic nanocatalyst for the synthesis of biologically active quinazoline derivatives.

Metal-organic frameworks (MOFs) offered excellent catalytic activity due to their superior porosity, and high densities of catalytic sites in remarkable specific surfaces. In this research, we prepared a magnetic nanocomposite based on MOF-5 which is one of the prominent and practical structures that have been reported in many applications, and investigated the advantages of it as a catalyst. The multi-functional catalyst was prepared in five steps including (1) preparation of cobalt ferrite nanoparticles (CoFe2O4), (2) surface modification of cobalt ferrite using tetraethyl orthosilicate, (3) surface functionalization using 3-aminopropyl triethoxysilane, (4) preparation of MOF-5, (5) preparation of CoFe2O4@SiO2-NH2@MOF-5 nanocomposite. The resulting catalyst was evaluated by FTIR, FESEM, EDX, XRD, and VSM analyses. The CoFe2O4@SiO2-NH2@MOF-5 nanocomposite was applied as a catalyst for the quinazoline derivatives' synthesis. Various products were prepared with significant yields (90-98%) in short reaction times (20-60 min) without difficult work-up. In addition, the magnetic behavior of the catalyst allows it to be collected and recycled by a magnet and applied for six consecutive cycles without significantly reducing its efficiency. Quinazoline derivatives showed significant biological activities so their antioxidant activity was between 23.7% and 88.9% and their antimicrobial activity was in contradiction of E. coli, S. enterica, L. monocytogenes, S. aureus, and E. faecalis.

All-in-one smart dressing for simultaneous angiogenesis and neural regeneration.

Wound repair, along with skin appendage regeneration, is challenged by insufficient angiogenesis and neural regeneration. Therefore, promoting both proangiogenic and neuro-regenerative therapeutic effects is essential for effective wound repair. However, most therapeutic systems apply these strategies separately or ineffectively. This study investigates the performance of an all-in-one smart dressing (ASD) that integrates angiogenic functional materials and multiple biological factors within a light crosslinked hydrogel, forming a multi-functional dressing capable of facilitating simultaneous micro-vascularization and neural regeneration. The ASD uses a zeolite-imidazolate framework 67 with anchored vanadium oxide (VO2@ZIF-67) that allows for the on-demand release of Co2+ with fluctuations in pH at the wound site to stimulate angiogenesis. It can simultaneously release CXCL12, ligustroflavone, and ginsenoside Rg1 in a sustained manner to enhance the recruitment of endogenous mesenchymal stem cells, inhibit senescence, and induce neural differentiation to achieve in situ nerve regeneration. The ASD can stimulate rapid angiogenesis and nerve regeneration within 17 days through multiple angiogenic and neuro-regenerative cues within one dressing. This study provides a proof-of-concept for integrating functional nanomaterials and multiple complementary drugs within a smart dressing for simultaneous angiogenesis and neural regeneration.

Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 µM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

Antioxidant, Collagenase Inhibitory, and Antibacterial Effects of Bioactive Peptides Derived from Enzymatic Hydrolysate of Ulva australis.

The protein extract of Ulva australis hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against Propionibacterium acnes, and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC50 values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti-P. Acnes effects, with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

Change Point Detection for Fine-Grained MFR Work Modes with Multi-Head Attention-Based Bi-LSTM Network.

Detection of the changes in Multi-Functional Radar (MFR) work modes is a critical situation assessment task for Electronic Support Measure (ESM) systems. There are two major challenges that must be addressed: (i) The received radar pulse stream may contain multiple work mode segments of unknown number and duration, which makes the Change Point Detection (CPD) difficult. (ii) Modern MFRs can produce a variety of parameter-level (fine-grained) work modes with complex and flexible patterns, which are challenging to detect through traditional statistical methods and basic learning models. To address the challenges, a deep learning framework is proposed for fine-grained work mode CPD in this paper. First, the fine-grained MFR work mode model is established. Then, a multi-head attention-based bi-directional long short-term memory network is introduced to abstract high-order relationships between successive pulses. Finally, temporal features are adopted to predict the probability of each pulse being a change point. The framework further improves the label configuration and the loss function of training to mitigate the label sparsity problem effectively. The simulation results showed that compared with existing methods, the proposed framework effectively improves the CPD performance at parameter-level. Moreover, the F1-score was increased by 4.15% under hybrid non-ideal conditions.

Universal Stress Proteins: From Gene to Function.

Universal stress proteins (USPs) exist across a wide range of species and are vital for survival under stressful conditions. Due to the increasingly harsh global environmental conditions, it is increasingly important to study the role of USPs in achieving stress tolerance. This review discusses the role of USPs in organisms from three aspects: (1) organisms generally have multiple USP genes that play specific roles at different developmental periods of the organism, and, due to their ubiquity, USPs can be used as an important indicator to study species evolution; (2) a comparison of the structures of USPs reveals that they generally bind ATP or its analogs at similar sequence positions, which may underlie the regulatory role of USPs; and (3) the functions of USPs in species are diverse, and are generally directly related to the stress tolerance. In microorganisms, USPs are associated with cell membrane formation, whereas in plants they may act as protein chaperones or RNA chaperones to help plants withstand stress at the molecular level and may also interact with other proteins to regulate normal plant activities. This review will provide directions for future research, focusing on USPs to provide clues for the development of stress-tolerant crop varieties and for the generation of novel green pesticide formulations in agriculture, and to better understand the evolution of drug resistance in pathogenic microorganisms in medicine.

How the environment evokes actions that lead to different goals: the role of object multi-functionality in pavlovian-to-instrumental transfer.

Research shows that stimuli in the environment can trigger behavior via the activation of goal representations. This process can be tested in the Pavlovian-to-Instrumental Transfer (PIT) paradigm, where stimuli can only affect behavior through the activation of the representation of its desired outcome (i.e., the PIT effect). Previous research has demonstrated that the PIT effect is stronger when the goal is more desirable. While this research only looked at actions that have single outcomes (e.g., obtaining a snack to satisfy appetite), in the present paper, we reason that actions that are instrumental in obtaining outcomes that are desirable in multiple ways (e.g., obtaining a snack to satisfy one's appetite, giving it to a friend, trading it for money) should produce stronger PIT effects. In two experiments, participants learned to perform left and right key presses to earn a snack, either framed as having a single function or multiple functions. Participants also learned to associate the two differently framed snacks with two cues. In a PIT test, they were required to press the keys as fast as possible upon exposure to the cues (i.e., the PIT effect). We found that cues associated with the multi-functional snack facilitated the actions that earned those snacks before, while cues associated with the single-functional snack did not facilitate such actions. We discuss these findings in the context of research on free choice and personal autonomy and how people appreciate the multi-functional nature of their goal-directed behavior in the environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04612-2.

High Performance Solid-State Lithium-Sulfur Battery Enabled by Multi-Functional Cathode and Flexible Hybrid Solid Electrolyte.

With its superior theoretical energy density as well as abundance and environment-friendliness, the lithium-sulfur battery (LiSB) is a potential candidate to replace the traditional energy storage and generation systems. An innovative design is proposed for the high-performance solid-state LiSB system by combining the multi-functional cathode comprising the sulfur-loaded Al2 O3 -modified carbon nanotubes (S@ACNTs) and the flexible hybrid solid electrolyte (HSE). Assembled with S@ACNTs active material, the polycation poly(diallyldimethylammonium bis(trifluoromethylsulfonyl)imide) (PDATFSI) binder exhibits high Li+ conductivity of 0.45 mS cm-1 at room temperature, good thermal stability up to 450 °C, high adhesive strength with aluminum current collector up to 24 MPa, sustainable non-flammability, and desirable flexibility. When assembled with HSE membrane, the S@ACNTs/PDATFSI-60IL cathode layer demonstrates effective polysulfide trapping behavior and superior compatibility (65 Ω), resulting in high discharge capacity of 1203 mAh g-1 at 0.2 C in the 1st cycle, and long-term stability up to 91.69% of the discharge capacity after 200 cycles of charge/discharge process.

Furanonyl amino acid derivatives as hemostatic drugs: design, synthesis and hemostasis performance.

Using 3,4-dihalo-2(5H)-furanones and easily available hemostatic drugs, such as tranexamic acid (TA), 4-aminomethylbenzoic acid (ABA), aminocaproic acid (AA) as starting materials, serial multi-functional molecules 2(5H)-furanonyl amino acids are designed by the combination of different pharmacophores, and successfully synthesized by a transition metal-free Michael addition-elimination reaction. The reaction is carried out under mild conditions with ethanol-dichloromethane as solvent and only stirring at room temperature for 24 h, and the yield can be up to 91%. All products are well characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), high-resolution mass spectra (HRMS). Ten typical target compounds among them are selected out for the experiments of hemostasis performance by the evaluation of in vitro clot formation model and liver hemorrhage model. The test results show that, their hemostasis effect is better than the original drugs. Especially the target compound G, a TA derivative from 5-borneoloxy-3,4-dibromo-2(5H)-furanone, has the best hemostasis effect among all the tested compounds. These obtained target molecules are expected to be used as multi-functional hemostatic drugs.

Edible films/coatings containing bioactive ingredients with micro/nano encapsulation: A comprehensive review of their fabrications, formulas, multifunctionality and applications in food packaging.

Due to the consumer's pursuit of safe, nontoxic and nutritious foods, edible and/or biodegradable materials have stood out in food packaging and preservation. In this context, the preparation and application of micro/nano encapsulated active ingredients (M/N-E-BAIs) represent a step toward reinforcing the properties of sustainable and controllable food packaging, particularly for the successful incorporation of new substances and functionalities into traditional edible films/coatings. This review, from the preparation of M/N-E-BAIs, the fabrication of edible film/coating containing M/N-E-BAIs to their characterization of multifunction and the application in food, makes a systematic summary and in-depth discussion. Food-grade polymers can encapsulate bioactive ingredients (BAIs) by chemical, physicochemical and mechanical methods, thereby forming M/N-E-BAIs with suitable sustained-release and unique biological activities. Furthermore, M/N-E-BAIs is incorporated into biopolymer substrates by solvent casting, 3D printing or electrostatic spinning to obtain novel edible films/coatings. This advanced packaging material exhibits superior physicochemical and functional properties over traditional food films/coatings. Besides, their applications in foods as active and intelligent packaging can improve food quality, prolong shelf life and monitor food corruption. Even so, there are still many challenges and limitations in formulation, preparation and application of this new packaging technology that need to be addressed in the future.

Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies.

Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy. Herein, a series of novel donepezil-chalone-rivastigmine hybrids was rationally designed and synthesized by fusing donepezil, chalone and rivastigmine. The in vitro bioactivity results displayed that compound 10c was a reversible huAChE (IC50 = 0.87 µM) and huBuChE (IC50 = 3.3 µM) inhibitor. It also presented significant anti-inflammation effects by suppressing the level of IL-6 and TNF-α production, and significantly inhibited self-mediated Aß1-42 aggregation (60.6%) and huAChE-mediated induced Aß1-40 aggregation (46.2%). In addition, 10c showed significant neuroprotective effect on Aß1-42-induced PC12 cell injury and activated UPS pathway in HT22 cells to degrade tau and amyloid precursor protein (APP). Furthermore, compound 10c presented good stabilty in artificial gastrointestinal fluids and liver microsomes in vitro. The pharmacokinetic study showed that compound 10c was rapidly absorbed in rats and distributed in rat brain after intragastric administration. The PET-CT imaging demonstrated that [11C]10c could quickly enter the brain and washed out gradually in vivo. Further, compound 10c at a dose of 5 mg/kg improved scopolamine-induced memory impairment, deserving further investigations.