20-esterification of 5-spiro CPT and their anticancer activity in vitro.

20-ester of 5-spirocycle campthothecin derivatives were successfully constructed and synthesised by Steglich esterification in a moderate yield. These derivatives showed a better solubility. Compared to parent compound, most of these 20-ester-5-spirocycle campthothecin derivatives (besides 3g) showed a better inhibition activity against HepG2 cell line.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

TEMPO/PhI(OAc)2 promotes the α-aminophosphinoylation of alcohols with amines and H-phosphine oxides in aqueous medium.

A novel method for synthesizing α-aminoalkyl phosphine oxides in aqueous medium, using Ar2P(O)-H reagents, alcohols and amines, is described. This method: (i) allows for the smooth aminophosphinoylation of alcohols with amines and H-phosphine oxides under mild conditions; (ii) provides an efficient and alternative approach to access various α-aminoalkylphosphine oxides. Although various amines exhibited remarkable versatility and tolerance for functional groups in this reaction, alcohols and H-phosphine oxides demonstrated limited applicability as reactants. Hence, further investigation using a wider range of substrates is crucial. The postulated mechanism indicated that the three-component reaction followed the imine pathway due to the in situ oxidation of alcohol to aldehyde.

UV absorption enhanced polydopamine coating.

Mussel-inspired polydopamine (PDA) coatings have gained significant attention in various fields, including biomedicine, energy, detection, and UV protection, owing to their versatile and promising properties. Among these properties, UV shielding stands out as a key feature of PDA coatings. Nevertheless, the current methods for tuning the UV-shielding properties of PDA coatings are quite limited, and only rely on thickness adjustment, which might involve additional issues like color and visible light transmittance to the coating layer. In this study, we propose a facile and modular approach to enhance the UV absorption of PDA coatings by incorporating thiol-heterocycle (TH) derivatives. Both pre- and post-modification strategies can effectively impede the formation of conjugated structures within PDA, leading to enhanced UV absorption within the PDA layers. More importantly, these strategies can improve the UV absorption of PDA coatings while reducing the visible light absorption. Furthermore, this method enabled efficient regulation of the UV absorption of PDA coatings by altering the ring type (benzene ring or pyridine ring) and substituent on the ring (methoxyl group or hydrogen atom). These PDA coatings with enhanced UV absorption demonstrate great promise for applications in UV protection, antibacterial activity, wound healing and dye degradation.

Eumelanin-like Poly(levodopa) Nanoscavengers for Inflammation Disease Therapy.

In the current years, polydopamine nanoparticles (PDA NPs) have been extensively investigated as an eumelanin mimic. However, unlike natural eumelanin, PDA NPs contain no 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-derived units and may be limited in certain intrinsic properties; superior eumelanin-like nanomaterials are still actively being sought. Levodopa (l-DOPA) is a natural eumelanin precursor and expected to convert into DHICA and further remain within the final product through covalent or physical interactions. Herein, poly(levodopa) nanoparticles [P(l-DOPA) NPs] were synthesized with the assistance of zinc oxide as a supplement to synthetic eumelanin. This study found that P(l-DOPA) NPs had ∼90% DHICA-derived subunits on their surface and exhibited superior antioxidant activity compared to PDA NPs due to their looser polymeric microstructure. Benefitting from a stronger ROS scavenging ability, P(l-DOPA) NPs outperformed PDA NPs in treating cellular oxidative stress and acute inflammation. This research opens up new possibilities for the development and application of novel melanin-like materials.

An in-depth survey on Deep Learning-based Motor Imagery Electroencephalogram (EEG) classification.

Electroencephalogram (EEG)-based Brain-Computer Interfaces (BCIs) build a communication path between human brain and external devices. Among EEG-based BCI paradigms, the most commonly used one is motor imagery (MI). As a hot research topic, MI EEG-based BCI has largely contributed to medical fields and smart home industry. However, because of the low signal-to-noise ratio (SNR) and the non-stationary characteristic of EEG data, it is difficult to correctly classify different types of MI-EEG signals. Recently, the advances in Deep Learning (DL) significantly facilitate the development of MI EEG-based BCIs. In this paper, we provide a systematic survey of DL-based MI-EEG classification methods. Specifically, we first comprehensively discuss several important aspects of DL-based MI-EEG classification, covering input formulations, network architectures, public datasets, etc. Then, we summarize problems in model performance comparison and give guidelines to future studies for fair performance comparison. Next, we fairly evaluate the representative DL-based models using source code released by the authors and meticulously analyse the evaluation results. By performing ablation study on the network architecture, we found that (1) effective feature fusion is indispensable for multi-stream CNN-based models. (2) LSTM should be combined with spatial feature extraction techniques to obtain good classification performance. (3) the use of dropout contributes little to improving the model performance, and that (4) adding fully connected layers to the models significantly increases their parameters but it might not improve their performance. Finally, we raise several open issues in MI-EEG classification and provide possible future research directions.

Synthesis of 3- and 5-ß-anhydroicaritine norcantharidin conjugates.

Using molecular hybridisation to develop conjugates of natural antitumor drugs is one of the research hotspots in recent drug development. In this study, ß-anhydroicaritine with anticancer activity was conjugated to norcantharidine selectively to develop new antitumor lead candidates. In the condition of EDCI/DMAP/DCM, the C-3 and C-5 hydroxyl groups of ß-anhydroicaritine was coupled with norcantharidin monoacid ester respectively, and the inhibitory activity of the synthesised conjugates against HepG2, MCF-7 and L-02 cells were tested by CCK-8 method. Most of these conjugates showed a better activity against HepG2 and MCF-7 cell lines compared to parent compound icaritin, but weaker than another parent compound norcantharidin.

Simultaneously mapping loci related to two plant architecture traits by phenotypic recombination BSA/BSR in peanut (Arachis hypogaea L.).

KEY MESSAGE: We developed a new method phenotypic recombination BSA/BSR (PR-BSA/BSR), which could simultaneously identify the candidate genomic regions associated with two traits in a segregating population. Bulked segregant analysis sequencing (BSA-seq) has been widely used for identifying the genomic regions affecting a certain trait. In this study, we developed a modified BSA/bulked segregant RNA-sequencing (BSR-seq) method, which we named phenotypic recombination BSA/BSR (PR-BSA/BSR), to simultaneously identify candidate genomic regions associated with two traits in a segregating population. Lateral branch angle (LBA) and flower-branch pattern (FBP) are two important traits associated with the peanut plant architecture because they affect the planting density and light use efficiency. We generated an F6 population (with two segregating traits) derived from a cross between the inbred lines Pingdu9616 (erect and sequential; ES-type) and Florunner (spreading and alternating; SA-type). The selection of bulks with extreme phenotypes was a key step in this study. Specifically, 30 individuals with recombinant phenotypes [i.e., spreading and sequential (SS-type) and erect and alternating (EA-type)] were selected to generate two bulks. The transcriptomes of individuals were sequenced and then the loci related to LBA and FBP were simultaneously detected via a ΔSNP-index strategy, which involved the direction of positive and negative peaks in the ∆SNP-index plot. The LBA-related locus was mapped to a 6.82 Mb region (101,743,223-108,564,267 bp) on chromosome 15, whereas the FBP-related locus was mapped to a 2.16 Mb region (117,682,534-119,846,824 bp) on chromosome 12. Furthermore, the marker-based classical QTL mapping method was used to analyze the PF-F6 population, which confirmed our PR-BSA/BSR results. Therefore, the PR-BSA/BSR method produces accurate and reliable data.

Glyco-conjugation in 3-ß-anhydroicaritine.

A convenient method has been developed for the glycol-conjugation in 3-position of ß-anhydroicaritine in a reasonable yield. The structure of the 3-glycosylated ß-anhydroicaritine derivatives was confirmed to be correct by 1H NMR, 13C NMR and HRMS spectrum. These compounds are less soluble than icaritin, but more soluble than icariside II in CCl4. The screening results showed that compounds 12h, 12i and 12j had higher cytotoxicity to HepG2 and MCF-7 at a concentration of 50 µM.

Size Regulation of Polydopamine Nanoparticles by Boronic Acid and Lewis Base.

Size regulation of polydopamine nanoparticles (PDA NPs) is vital to melanin-inspired materials. The general strategy usually focuses on tuning of the reaction parameters which could affect the dopamine (DA) monomer polymerization process, such as pH, temperature, monomer concentration, etc. The reaction between boronic acids and catechols to form boronic esters has been widely applied in many fields, but little attention has been paid in the size regulation of PDA NPs. Here, it is speculated that the fine size regulation of PDA NPs can be directly achieved by using boronic acids and Lewis base molecules. It is found that these issues could indeed significantly affect the stability of the boronic esters formed by boronic acids and DA, which may further inhibit the monomer polymerization kinetics and tune the particle size of the resulting PDA NPs. It is also found that the several intrinsic properties of PDA NPs such as the free radical scavenging ability, UV spectral absorption, photothermal behavior, and structural color all change with the particle size. It is believed that this work can provide new opportunities for fabricating melanin-inspired PDA NPs with well controlled size and properties.

Regio-selective synthesis and activity research on 7-icaritin norcantharidin conjugates.

Due to complexity of tumor diseases and resistance of targeted drug, targeted drug usually cannot meet the needs of cancer treatment. Therefore, the conjugate constructed by two anticancer agents maybe a better solution for the tumor diseases. As natural anticancer agents, icaritin and norcantharidin are selected for the construction of conjugate. In the condition of EDCI/DMAP, icaritin is reacted with norcantharidin esters to give the desired 7-esters selectively in a moderate yield. MTT method was used to test the cytotoxicity and intensity on Hep G2 and MCF-7 in vitro. Some of the compounds (4a, 4i and 4j) show a better inhibition against Hep G2 and MCF-7 cell lines in vitro, and are deserved to be a potential drug candidate to develop in vivo.

Synthesis of l-ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro.

Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1HNMR, 13CNMR and MS spectrum. The results showed that compounds 6e, 6g, 6j, 6l, 6m, 6b, 6e, 6i, and 6n showed high cytotoxicity to HepG2 and compounds 6b, 6e-g, 6l, 6n, 7b, 7d, 7h, 7i, 7n, 8g, 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b, 6e, 6g, and 6k, the other compounds showed less toxic to LO2 at a concentration of 50 µg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.

Selective alkylation of ß-anhydroicaritine and their biological evaluation on anticancer.

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of ß-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated ß-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen.

Synthesis of ring opening of evodiamine derivatives and evaluation on their biological activity.

As a main bioactive component extracted from Evodiae fructus, evodiamine has a variety of pharmacological activities. In this paper, evodiamine was chosen as starting material to react with different halides. Upon treatment of TFA, a series of novel ring-opening evodiamine derivatives 3a-o were successfully synthesized in a moderate to high yields. These obtained compounds exhibit a moderate to good antitumor activity against BGC803 and SW480 in vitro test by MTT assay. The results showed that hexyl substituted evodiamine derivative (3j, R=hexyl) has a strong antitumor activity against BGC803 and SW480.

Synthesis and biological evaluation of camptothecin substituted norcantharimide derivatives.

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803.

A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.

A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I. The total yield can reach 71%. This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues. The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.