Two New α-Glucosidase Inhibitory Depsidones from the Lichen Parmotrema cristiferum (Taylor) Hale.

A bioactivity-guided investigation of the lichen Parmotrema cristiferum (Taylor) Hale (Parmeliaceae) led to the isolation of two new depsidones, cristifones A and B (1 and 2). The structures of the isolated compounds were identified by spectroscopic methods and comparison with the literature data. Compound 1 showed the initial combined structures of depsidone and depside cores. The two isolated compounds were then evaluated for α-glucosidase inhibition. Compounds 1 and 2 were confirmed as potent, with IC50 values of 21.5 and 18.4 µM, respectively. Compound 2 was a non-competitive inhibitor against α-glucosidase, as indicated by the intersect in the second quadrant of each respective plot.

Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders.

Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system's structure and function due to oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation. Among these NDs, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis characterized an increasing dysfunction and loss of neuronal structure leading to neuronal cell death. Although there is currently no drug to totally reverse the effects of NDs, such novel formulations and administration routes are developed for better management and nose-to-brain delivery is one of delivery for treating NDs. This review aimed to highlight advances in research on various lipid based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and cubosomes which are reported to treat and alleviate the symptoms of NDs via nose-to-brain route. The challenges during clinical translation of lipid nanocarriers from bench to bed side is also discussed.

Basal Plane Functionalization of Niobium Disulfide Nanosheets with Cyclopentadienyl Manganese(I) Dicarbonyl.

Basal plane-functionalized NbS2 nanosheets were obtained using in situ photolysis to generate the coordinatively unsaturated organometallic fragment cyclopentadienyl manganese(I) dicarbonyl (CpMn(CO)2). Under UV irradiation, a labile carbonyl ligand dissociates from the tricarbonyl complex, creating an open coordination site for bonding between the Mn atom and the electron-rich sulfur atoms on the surface of the NbS2 nanosheets. In contrast, no reaction is observed with 2H-MoS2 nanosheets under the same reaction conditions. This difference in reactivity is consistent with the electronic structure calculations, which indicate stronger bonding of the organometallic fragment to electron-poor, metallic NbS2 than to semiconducting, electron-rich MoS2. X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used to characterize the bonding between Mn and S atoms on the surface-functionalized nanosheets.

α-Glucosidase Inhibitory and Antimicrobial Benzoylphloroglucinols from Garcinia schomburgakiana Fruits: In Vitro and In Silico Studies.

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus.

Microneedles enable the development of skin-targeted vaccines against coronaviruses and influenza viruses.

Throughout the COVID-19 pandemic, many have seriously worried that the plus burden of seasonal influenza that might create a destructive scenario, resulting in overwhelmed healthcare capacities and onwards loss of life. Many efforts to develop a safe and efficacious vaccine to prevent infection by coronavirus and influenza, highlight the importance of vaccination to combat infectious pathogens. While vaccines are traditionally given as injections into the muscle, microneedle (MN) patches designed to precisely deliver cargos into the cutaneous microenvironment, rich in immune cells, provide a noninvasive and self-applicable vaccination approach, reducing overall costs and improving access to vaccines in places with limited supply. The current review aimed to highlight advances in research on the development of MNs-mediated cutaneous vaccine delivery. Concluding remarks and challenges on MNs-based skin immunization are also provided to contribute to the rational development of safe and effective MN-delivered vaccines against these emerging infectious diseases.

In silico and in vitro studies on the anti-cancer activity of artemetin, vitexicarpin and penduletin compounds from Vitex negundo.

Vitex negundo L. (V. negundo) is one of the important medicinal and anticancer enhancer herbs. This plant is commonly used in the preparation of traditional drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the current study aimed to investigate antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human HepG2 and MCF-7 cell lines, by pure compounds isolated from targeted fractions of V. negundo which were characterized by NMR, FTIR and HRMS analysis and identified as artemetin (FLV1), vitexicarpin (FLV2), and penduletin (FLV3) compounds. The FLV1, FLV2, and FLV3 compounds were evaluated for the antiproliferative potential against HepG2 and MCF-7 cell lines by cell viability assay and exhibited IC50 values of 2.3, 23.9 and 5.6 µM and 3.9, 25.8, and 6.4 µM, respectively. In addition, those compounds increased the level of reactive oxygen species production, induced cell death occurred via apoptosis, demonstrated by Annexin V-staining cells, contributed significantly to DNA damage, and led to the activation of caspase3/caspase8 pathways.Additionally, molecular docking was also conducted to rationalize the cancer cells inhibitory and to evaluate the ability of the FLV1, FLV2, and FLV3 compounds to be developed as good drug candidates for cancers treatment.

Identification of Highly Potent α-Glucosidase Inhibitors from Artocarpus integer and Molecular Docking Studies.

A new natural Diels-Alder adduct (3) was isolated from the leaves and stem bark of Artocarpus integer, along with seventeen known compounds (1, 2, and 4-18). Structural elucidation was conducted using NMR and HR-ESI-MS data, and comparisons were made with previous studies. Deoxyartonin I (3) exhibited the most potent α-glucosidase inhibition (IC50 7.80±0.1 µM), outperforming the acarbose positive control. This was mixed-mode inhibition, as indicated by the intersect in the second quadrant of each respective plot. An in silico molecular docking model and the pharmacokinetic features of 3 suggest that it is a potential inhibitor of enzyme α-glucosidase, and is therefore a lead candidate as a drug against diabetes mellitus.

Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam.

Bioactive-guided phytochemical investigation of Euphorbia antiquorum L. growing in Vietnam led to the isolation of five ent-atisanes, one seco-ent-atisane, and one lathyrane (ingol-type). The structures were elucidated as ent-1α,3α,16ß,17-tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylate (2), ent-atisane-3-oxo-16ß,17-acetonide (3), ent-3α-acetoxy-16ß,17-dihydroxyatisane (4), ent-16ß,17-dihydroxyatisane-3-one (5), calliterpenone (6), and ingol 12-acetate (7). Their chemical structures were unambiguously determined by analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry, as well as by comparison with literature data. Among them, 1 is a new compound while 2 is an ethylated artifact of ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylic acid, a new compound. Isolates were evaluated for alpha-glucosidase inhibition. Compound 3 showed the most significant inhibitory activity against alpha-glucosidase with an IC50 value of 69.62 µM. Further study on mechanism underlying yeast alpha-glucosidase inhibition indicated that 3 could retard the enzyme function by noncompetitive.

Flavones from Combretum quadrangulare Growing in Vietnam and Their Alpha-Glucosidase Inhibitory Activity.

Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.

Synthesis, α-glucosidase inhibition, and molecular docking studies of novel N-substituted hydrazide derivatives of atranorin as antidiabetic agents.

A series of novel N-substituted hydrazide derivatives were synthesized by reacting atranorin, a compound with a natural depside structure (1), with a range of hydrazines. The natural product and 12 new analogues (2-13) were investigated for inhibition of α-glucosidase. The N-substituted hydrazide derivatives showed more potent inhibition than the original. The experimental results were confirmed by docking analysis. This study suggests that these compounds are promising molecules for diabetes therapy. Molecular dynamics simulations were carried out with compound 2 demonstrating the best docking model using Gromac during simulation up to 20 ns to explore the stability of the complex ligand-protein. Furthermore, the activity of all synthetic compounds 2-13 against a normal cell line HEK293, used for assessing their cytotoxicity, was evaluated.

Nervisides I-J: Unconventional Side-Chain-Bearing Cycloartane Glycosides from Nervilia concolor.

Two new cycloartane glycosides, nervisides I-J, were isolated from Nervilia concolor whole plants. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data. These cycloartanes comprised a stereogenic center at C-24, the R configuration of which was assigned based on DFT-NMR calculations and the subsequent DP4 probability score. These compounds were tested for cytotoxicity against K562 and MCF-7 tumor cell lines, revealing mild cytotoxic activity.

Controlled Exfoliation of MoS2 Crystals into Trilayer Nanosheets.

The controlled exfoliation of transition metal dichalcogenides (TMDs) into pristine single- or few-layer nanosheets remains a significant barrier to fundamental studies and device applications of TMDs. Here we report a novel strategy for exfoliating crystalline MoS2 into suspensions of nanosheets with retention of the semiconducting 2H phase. The controlled reaction of MoS2 with substoichiometric amounts n-butyllithium results in intercalation of the edges of the crystals, which are then readily exfoliated in a 45 vol % ethanol-water solution. Surprisingly, the resulting colloidal suspension of nanosheets was found (by electron microscopy and atomic force microscopy) to consist mostly of trilayers. The efficiency of exfoliation of the pre-intercalated sample is increased by at least 1 order of magnitude relative to the starting MoS2 microcrystals, with a mass yield of the dispersed nanosheets of 11-15%.

Fast and Efficient Preparation of Exfoliated 2H MoS2 Nanosheets by Sonication-Assisted Lithium Intercalation and Infrared Laser-Induced 1T to 2H Phase Reversion.

Exfoliated 2H molybdenum disulfide (MoS2) has unique properties and potential applications in a wide range of fields, but corresponding studies have been hampered by the lack of effective routes to it in bulk quantities. This study presents a rapid and efficient route to obtain exfoliated 2H MoS2, which combines fast sonication-assisted lithium intercalation and infrared (IR) laser-induced phase reversion. We found that the complete lithium intercalation of MoS2 with butyllithium could be effected within 1.5 h with the aid of sonication. The 2H to 1T phase transition that occurs during the lithium intercalation could be also reversed by IR laser irradiation with a DVD optical drive.

Air-coupled ultrasonic transducer based on lead-free piezoceramics prepared by digital light processing 3D printing.

Piezoelectric composite ceramics, as the key components of ultrasonic transducers, have their vibration modes, electromechanical coupling performance, and acoustic impedance closely related to the volume fraction of ceramics. This study employed a novel digital light processing 3D printing technique (DLP) to fabricate 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (BCZT)-based 1-3 piezoelectric composite ceramics with different ceramic volume fractions (15.6 %, 23.5 %, 36.2 %, 48.4 %, 59.5 %). It demonstrates the suitability of the DLP process for the fabrication of 1-3 piezoelectric composite ceramics and investigates the influence of ceramic volume fraction on the performance of these ceramics. When the piezoelectric ceramic volume fraction was 59.5 %, the piezoelectric coefficient effective d33 of the 1-3 piezoelectric composite device reached 315 pC/N, demonstrating excellent piezoelectric performance. The acoustic impedance Z was 16.3 MRayl, and the thickness electromechanical coupling coefficient kt was 0.55, indicating high energy conversion efficiency. The air-coupled ultrasonic transducer prepared from the 1-3 piezoelectric composite ceramics with a ceramic volume fraction of 59.5 % exhibited a round-trip insertion loss (IL) of -70.32 dB and a -6 dB bandwidth (BW-6dB) of 7.42 %. This work provides a more convenient and new method for the preparation of lead-free piezoelectric ceramic ultrasonic transducers.

α-Glucosidase inhibitory activities of flavonoid derivatives isolated from Bouea macrophylla: in vitro and in silico studies.

In continuation of our search for bioactive compounds from the Bouea macrophylla (B. macrophylla) plant, we describe herein eight flavonoid-type compounds including mearsetin (1), mearnsitrin (2), kampferol (3), afzelin (4), quercetin (5), quercitrin (6), myricitin (7), and naringenin (8) with the aim of investigating their antidiabetic properties. Compounds 3 and 5 were selected for aromatic bromination to provide two new products 3a and 5a, respectively. All compounds showed promising α-glucosidase inhibition, with IC50 values ranging from 9.2 to 266 µM apart from compound (2). Remarkably, compound 5a, 8-bromoquercetin, showed the highest inhibition activity, and it was thirty-seven times better than the standard drug acarbose. Pose 261/compound 5a interacted well with enzyme 3TOPin silico docking, and the complex of pose 261 and target enzyme proved its stability in MD. Compound 5a, pose 261 was predicted to be safe and seemed to have good absorption, distribution, metabolism, and excretion properties as assessed via the ADMET model in silico. Our findings revealed the α-glucosidase inhibitory potential of the flavonoids isolated from the leaves of B. macrophylla with a predictive pharmacokinetics profile, which may be helpful in their development as potential drugs.

Recent Advancements in Nanomaterials: A Promising Way to Manage Neurodegenerative Disorders.

Neurodegenerative diseases (NDs) such as dementia, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis are some of the most prevalent disorders currently afflicting healthcare systems. Many of these diseases share similar pathological hallmarks, including elevated oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation, all of which contribute to the deterioration of the nervous system's structure and function. The development of diagnostic and therapeutic materials in the monitoring and treatment of these diseases remains challenging. One of the biggest challenges facing therapeutic and diagnostic materials is the blood-brain barrier (BBB). The BBB is a multifunctional membrane possessing a plethora of biochemical, cellular, and immunological features that ensure brain homeostasis by preventing the entry and accumulation of unwanted compounds. With regards to neurodegenerative diseases, the recent application of tailored nanomaterials (nanocarriers and nanoparticles) has led to advances in diagnostics and therapeutics. In this review, we provide an overview of commonly used nanoparticles and their applications in NDs, which may offer new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.

Advances of microneedles in hormone delivery.

The skin is recognized as a potential target for local and systemic drug delivery and hormone. However, the transdermal route of drug administration seems to be limited by substantial barrier properties of the skin. Recently, delivering hormone via the skin by transdermal patches is a big challenge because of the presence of the stratum corneum that prevents the application of hormone via this route. In order to overcome the limitations, microneedle (MN), consisting of micro-sized needles, are a promising approach to drill the stratum corneum and release hormone into the dermis via a minimal-invasive route. This review aimed to highlight advances in research on the development of MNs-based therapeutics for their implications in hormone delivery. The challenges during clinical translation of MNs from bench to bedside are also discussed.

Maydisone, a novel oxime polyketide from the cultures of Bipolaris maydis.

A novel oxime polyketide, maydisone (1), along with two known compounds, 7-hydroxy-2,5-dimethylchromone (2) and 2,5-dimethylbenzoic acid (3) were isolated from the cultures of Bipolaris maydis. Their structures were identified by the application of NMR and MS data analyses and comparison with previous reports. Compound 1 showed the most powerful inhibition of α-glucosidase, with an IC50 value of 68.30 ± 0.83 µM.

Enhanced Dielectric Energy Storage Performance of 0.45Na0.5Bi0.5TiO3-0.55Sr0.7Bi0.2TiO3/AlN 0-3 Type Lead-Free Composite Ceramics.

Na0.5Bi0.5TiO3 (NBT) ceramic is the promising dielectric material for energy storage devices due to its high maximum polarizability and temperature stability. However, its low breakdown strength limits its application. Here, we prepared 0-3 type composite 0.45Na0.5Bi0.5TiO3-0.55Sr0.7Bi0.2TiO3/x wt % AlN (NBT-SBT/xAlN) to increase the breakdown strength. The effects of the various AlN contents on the phase composition, microstructures, dielectric, and energy storage properties of NBT-SBT were systematically discussed. The result showed that the enhanced energy storage properties were obtained by introducing AlN particles. The NBT-SBT/6AlN composite ceramics showed a high breakdown strength of 360 kV/cm, large energy density of 5.53 J/cm3, and energy efficiency of 90%. Meanwhile, the excellent frequency (10-500 Hz) and temperature stability (25-125 °C) were exhibited with the fluctuation of energy storage within 9% and energy efficiency more than 87%, suggesting that the 0-3 composite NBT-SBT/xAlN is a candidate dielectric material for the dielectric energy storage.

Nervione, a new benzofuran derivative from Nervilia concolor.

A new benzofuran derivative, nervione (1), was isolated from Nervilia concolor (Blume) Schltr. (Orchidaceae). Eight previously reported compounds were also isolated: 5,7-dimethoxyflavone (2), 3,5,7-trimethoxyflavone (3), 7-methoxyflavone (4), 3,7-dimethoxy-5-hydroxyflavone (5), tetramethylscutellarein (4',5,6,7-tetramethoxyflavone) (6), 5,7-dimethoxy-4'-hydroxyflavone (7), rhamnetin (8), and 5,7-dihydroxy-3',4'-dimethoxyflavone (9). The structures were elucidated by 1D, 2D NMR, and HRESIMS spectroscopy in addition to the literature. The relative configuration of 1 was defined using DP4+ probability while its absolute configuration was defined by comparison of the ECD spectrum of 1 with those of previously reported compounds. All isolated compounds were evaluated for alpha-glucosidase inhibition, revealing weak or no activity.[Formula: see text].