Bacterial polyynes uncovered: a journey through their bioactive properties, biosynthetic mechanisms, and sustainable production strategies.

Covering: up to 2023Conjugated polyynes are natural compounds characterized by alternating single and triple carbon-carbon bonds, endowing them with distinct physicochemical traits and a range of biological activities. While traditionally sourced mainly from plants, recent investigations have revealed many compounds originating from bacterial strains. This review synthesizes current research on bacterial-derived conjugated polyynes, delving into their biosynthetic routes, underscoring the variety in their molecular structures, and examining their potential applications in biotechnology. Additionally, we outline future directions for metabolic and protein engineering to establish more robust and stable platforms for their production.

Polyvinylidene Fluoride Based Piezoelectric Composites with Strong Interfacial Adhesion via Click Chemistry for Self-Powered Flexible Sensors.

Achieving relatively uniform dispersion in organic-inorganic composites with overwhelming differences in surface energy is a perennial challenge. Herein, novel eliminated polyvinylidene fluoride (EPVDF)/EPVDF functionalized barium titanate nanoparticles (EPVDF@BT) flexible piezoelectric nanogenerators (PENGs) with strong interfacial adhesion are developed via thermal stretching following sequential click chemistry. Thanks to the strong interfacial adhesion, the optimal PENGs containing ultra-high ß-phase content (97.2%) exhibit not only optimized mechanical and dielectric behaviors but also excellent piezoelectric properties with high piezoelectric output (V = 10.7 V, I = 216 nA), reliable durability (8000 cycles), ultrafast response time (20 ms), and good sensitivity (2.09 nA kPa-1), far outperforming most reported PVDF-based composites. Furthermore, COMSOL finite element simulations (FEM) confirm that the elevated stress transfer efficiency induced by the strong interfacial adhesion is the main driving force for enhanced piezoelectric performances. For practical applications, self-powered PENGs can simply but stably capture mechanical energy, drive tiny electronic devices, and serve as potential multifunctional and durable sensors for detecting human physiological motions. This work opens a pioneering avenue to break the trade-offs between piezoelectric and other properties, which is of great importance for developing self-powered flexible sensors.

Understanding the application of covalent adaptable networks in self-repair materials based on molecular simulation.

Covalent adaptable networks (CANs) are widely used in the field of self-repair materials. They are a group of covalently cross-linked associative polymers that undergo reversible chemical reactions, and can be further divided into dissociative CANs (Diss-CANs) and associative CANs (Asso-CANs). Self-repair refers to the ability of a material to repair itself without external intervention, and can be classified into self-adhesion and self-healing according to the utilization of open stickers. Unlike conventional materials, the viscoelastic properties of CANs are influenced by both the molecular structure and reaction kinetics, ultimately affecting their repair performance. To gain deeper insight into the repair mechanism of CANs, we conducted simulations by using the hybrid MC/MD algorithm, as previously proposed in our research. Interestingly, we observed a significant correlation between reaction kinetics and repair behavior. Asso-CANs exhibited strong mechanical strength and high creep resistance, rendering them suitable as self-adhesion materials. On the other hand, Diss-CANs formed open stickers that facilitated local relaxation, aligning perfectly with self-healing processes. Moreover, the introduction of crosslinkers in the form of small molecules enhanced the repair efficiency. Theoretically, it was found that the repair timescale of Asso-CANs is slower than that of Diss-CANs with identical molecular structures. Our study not only clarifies the similarities and differences between Diss-CANs and Asso-CANs in terms of their self-repairing capabilities, but more importantly, it provides valuable insights guiding the effective utilization of CANs in the development of self-repair materials.

Dimethyl sulfoxide, an alternative for control of Nosema ceranae infection in honey bees (Apis mellifera).

Nosema ceranae is a microsporidian parasite that threatens current apiculture. N. ceranae-infected honey bees (Apis mellifera) exhibit morbid physiological impairments and reduced honey production, malnutrition, shorter life span, and higher mortality than healthy honey bees. In this study, we found that dimethyl sulfoxide (DMSO) could enhance the survival rate of N. ceranae-infected honey bees. Therefore, we investigated the effect of DMSO on N. ceranae-infected honey bees using comparative RNA sequencing analysis. Our results revealed that DMSO was able to affect several biochemical pathways, especially the metabolic-related pathways in N. ceranae-infected honey bees. Based on these findings, we conclude that DMSO may be a useful alternative for treating N. ceranae infection in apiculture.

Naphthalene Diimide-Functionalized Half-Sandwich Ru(II) Complexes as Mitochondria-Targeted Anticancer and Antimetastatic Agents.

In this work, four naphthalene diimide (NDI)-functionalized half-sandwich Ru(II) complexes Ru1-Ru4 bearing the general formula [(η6-arene)RuII(N^N)Cl]PF6, where arene = benzene (bn), p-cymene (p-cym), 1,3,5-trimethylbenzene (tmb), and hexamethylbenzene (hmb), have been synthesized and characterized. By introducing the NDI unit into the N,N-chelating ligand of these half-sandwich complexes, the poor luminescent half-sandwich complexes are endowed with excellent emission performance. Besides, modification on the arene ligand of arene-Ru(II) complexes can influence the electron density of the metal center, resulting in great changes in the kinetic properties, catalytic activities in the oxidative conversion of NADH to NAD+, and biological activities of these compounds. Particularly, Ru4 exhibits the highest reactivity and the strongest inhibitory activity against the growth of three tested cancer cell lines. Further study revealed that Ru4 can enter cells quickly in an energy-dependent manner and preferentially accumulate in the mitochondria of MDA-MB-231 cells, inducing cell apoptosis via reactive oxygen species overproduction and mitochondrial dysfunction. Significantly, Ru4 can effectively inhibit the cell migration and invasion. Overall, the complexation with NDI and modification on the arene ligand endowed the half-sandwich Ru(II) complexes with improved spectroscopic properties and anticancer activities, highlighting their potential applications for cancer treatment.

A systematic study on immiscible binary systems undergoing thermal/photo reversible chemical reactions.

In this work, we systematically study an immiscible binary system undergoing thermal/photo reversible reactions in theory. For the thermal reaction case, no dissipative structures can be formed and only uniform equilibrium states are observed but the dynamical evolution to these trivial states witnesses a new type of sophisticated phase amplification phenomenon-temporary phase separation (TPS). Linear analysis and light-scattering calculations confirm that TPS is predominated either by spinodal decomposition or nucleation and growth mechanism, or by both successively. For the photo reaction case, steady dissipative patterns exist and are maintained by the external energy input of lights. Linear analysis together with simulations reveals that the characteristic wavelength (ξ) of these structures shortens as the input energy density increases and they obey the relation of ln ξ∝ 1/Tb with Tb the effective temperature of lights. The TPS phenomenon and length-scale dependency of dissipative patterns observed in this simple binary system might have rich implications for the non-equilibrium thermodynamics of biological systems.

Integrated metabolomics and network pharmacology to reveal the mechanism of areca nut addiction.

As a chewing hobby, areca nut (Areca catechu L.) has become the most common psychoactive substance in the world, besides tobacco, alcohol and caffeinated beverages. Moreover, as a first-class carcinogen designated by International Agency for Research on Cancer, long-term chewing areca nut can result in oral mucosal diseases and even oral cancer. To clarify the potential mechanism of areca nut addiction, an integrated strategy of metabolomics and network pharmacology was adopted in this study. Network pharmacology study indicated that all the key targets related to areca nut addiction could be regulated by arecoline and pointed out the importance of G-protein coupled receptor signalling pathway. Analysis results of mice plasma metabolome and faeces metabolome intervened by arecoline suggested that the component may affect the dopamine system and 5-HT system by regulating phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and intestinal flora structure. Moreover, the potential importance of bile acids in formation of addictive behaviour of chewing areca nut was investigated by integrative analysis of the relationships between metabolites and intestinal flora. The study can provide scientific basis for the addiction intervention and treatment of areca nut chewers.

Thermal, Rheological, Structural and Adhesive Properties of Wheat Starch Gels with Different Potassium Alum Contents.

Wheat starch (WS) is a common adhesive material used in mounting of calligraphy and paintings. Potassium alum (PA) has indeed been used for many centuries to modify the physicochemical properties of starch. Thermal analysis revealed that the presence of PA led to an increase in the gelatinization temperature and enthalpy of the starch gels. The leached amylose and the swelling power of the starch gels exhibited a maximum at the ratio of 100:6.0 (WS:PA, w/w). The rheological properties of starch gels were consistent with changes in the swelling power of starch granules. SEM observations confirmed that the gel structure became more regular, and the holes grew larger with the addition of PA below the ratio of 100:6.0 (WS:PA, w/w). The short-range molecular order in the starch gels was enhanced by the addition of PA, confirmed by FT-IR analysis. Mechanical experiments demonstrated that the binding strength of the starch gels increased with higher PA concentrations and decreased significantly after the aging process. TGA results revealed that PA promoted the acid degradation of starch molecules. This study provides a detailed guide for the preparation of starch-based adhesive and its applications in paper conservation.

An Investigation into the Performance and Mechanisms of Soymilk-Sized Handmade Xuan Paper at Different Concentrations of Soymilk.

Invaluable paper relics that embody a rich traditional culture have suffered damage, requiring urgent restoration. In this context, the utilization of soymilk as a sizing agent holds great significance and reverence. This study investigates the use of soymilk as a sizing agent for Xuan paper and evaluates its effects on various properties and the long-term behavior of the paper. The findings reveal that the application of soymilk as a sizing agent for Xuan paper imparts distinct properties, including hydrophobicity, improved mechanical properties, and unique chromaticity. These characteristics-arising from the papillae on the surface of the Xuan paper, the protein folding of the soy protein, and hydrogen-bonding interactions between the soy protein and paper fibers-play a crucial role in shaping the paper's unique attributes. From a physicochemical perspective, the aging process leads to multiple changes in paper properties. These changes include acidification, which refers to a decrease in pH, as well as a decline in mechanical strength, an increase in chromaticity, and a decrease in the degree of polymerization (DP) of the paper. The Ekenstam equation is employed to predict the lifespan of the paper, showing longer lifespans for Sheng Xuan paper and a negative correlation between soymilk concentration and lifespan in soymilk-sized paper. Our work provides valuable insights for the preservation and maintenance of paper, highlighting the potential benefits and challenges of using soymilk for surface sizing.

Visualizing vinca alkaloids in the petal of Catharanthus roseus using functionalized titanium oxide nanowire substrate for surface-assisted laser desorption/ionization imaging mass spectrometry.

Imaging mass spectrometry (IMS) is a powerful technique that enables analysis of various molecular species at a high spatial resolution with low detection limits. In contrast to the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) approach, surface-assisted laser desorption/ionization (SALDI) can be more effective in the detection of small molecules due to the absence of interfering background signals in low m/z ranges. We developed a functionalized TiO2 nanowire as a solid substrate for IMS of low-molecular-weight species in plant tissues. We prepared TiO2 nanowires using an inexpensive modified hydrothermal process and subsequently functionalized them chemically with various silane analogs to overcome the problem of superhydrophilicity of the substrate. Chemical modification changed the selectivity of imprinting of samples deposited on the substrate surface and thus improved the detection limits. The substrate was applied to image distribution of the metabolites in very fragile specimens such as the petal of Catharanthus roseus. We observed that the metabolites are distributed heterogeneously in the petal, which is consistent with previous results reported for the C. roseus plant leaf and stem. The intermediates corresponding to the biosynthesis pathway of some vinca alkaloids were clearly shown in the petal. We also performed profiling of petals from five different cultivars of C. roseus plant. We verified the semi-quantitative capabilities of the imprinting/imaging approach by comparing results using the LC-MS analysis of the plant extracts. This suggested that the functionalized TiO2 nanowire substrate-based SALDI is a powerful technique complementary to MALDI-MS.

Microbial polyketides and their roles in insect virulence: from genomics to biological functions.

Covering: May 1966 up to January 2022Entomopathogenic microorganisms have potential for biological control of insect pests. Their main secondary metabolites include polyketides, nonribosomal peptides, and polyketide-nonribosomal peptide (PK-NRP) hybrids. Among these secondary metabolites, polyketides have mainly been studied for structural identification, pathway engineering, and for their contributions to medicine. However, little is known about the function of polyketides in insect virulence. This review focuses on the role of bacterial and fungal polyketides, as well as PK-NRP hybrids in insect infection and killing. We also discuss gene distribution and evolutional relationships among different microbial species. Further, the role of microbial polyketides and the hybrids in modulating insect-microbial symbiosis is also explored. Understanding the mechanisms of polyketides in insect pathogenesis, how compounds moderate the host-fungus interaction, and the distribution of PKS genes across different fungi and bacteria will facilitate the discovery and development of novel polyketide-derived bio-insecticides.

The brown root rot fungus Phellinus noxius affects microbial communities in different root-associated niches of Ficus trees.

Brown root rot (BRR) caused by Phellinus noxius is a destructive tree disease in tropical and subtropical areas. To understand how BRR affects the composition of the plant rhizoplane-enriched microbiota, the microbiomes within five root-associated compartments (i.e., bulk soil, old/young root rhizosphere soil, old/young root tissue) of Ficus trees naturally infected by P. noxius were investigated. The level of P. noxius infection was determined by quantitative PCR. Illumina sequencing of the internal transcribed spacer and 16S rRNA revealed that P. noxius infection caused a significant reduction in fungal diversity in the bulk soil, the old root rhizosphere soil, and the old root tissue. Interestingly, Cosmospora was the only fungal genus positively correlated with P. noxius. The abundance and composition of dominant bacterial taxa such as Actinomadura, Bacillus, Rhodoplanes, and Streptomyces differed between BRR-diseased and healthy samples. Furthermore, 838 isolates belonging to 26 fungal and 35 bacterial genera were isolated and tested for interactions with P. noxius. Antagonistic activities were observed for isolates of Bacillus, Pseudomonas, Aspergillus, Penicillium, and Trichoderma. Cellophane overlay and cellulose/lignin utilization assays suggested that Cosmospora could tolerate the secretions of P. noxius and that the degradation of lignin by P. noxius may create suitable conditions for Cosmorpora growth.

The Potential Biocontrol Agent Paenibacillus polymyxa TP3 Produces Fusaricidin-Type Compounds Involved in the Antagonism Against Gray Mold Pathogen Botrytis cinerea.

Paenibacillus polymyxa is a beneficial bacterium for plant health. P. polymyxa TP3 exhibits antagonistic activity toward Botrytis cinerea and alleviates gray mold symptoms on the leaves of strawberry plants. Moreover, suppression of gray mold on the flowers and fruits of strawberry plants in field trials, including vegetative cells and endospores, was demonstrated, indicating the potential of strain TP3 as a biological control agent. To examine the anti-B. cinerea compounds produced by P. polymyxa TP3, we performed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and fusaricidin-corresponding mass spectra were detected. Moreover, fusaricidin-related signals appeared in imaging mass spectrometry of TP3 when confronted with B. cinerea. By using liquid chromatography mass spectrometry-based molecular networking approach, we identified several fusaricidins including a new variant of mass/charge ratio 917.5455 with serine in the first position of the hexapeptide. Via advanced mass spectrometry and network analysis, fusaricidin-type compounds produced by P. polymyxa TP3 were efficiently disclosed and were presumed to play roles in the antagonism against gray mold pathogen B. cinerea.

Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway.

Angiogenetic inhibitors are crucial in tumor therapy, and endogenous angiogenesis inhibitors have attracted considerable attention due to their effectiveness, safety, and multi-targeting ability. Arresten and canstatin, which have anti-angiogenesis effects, are the c-terminal fragments of the α1 and α2 chains of type IV collagen, respectively. In this study, human arresten and canstatin were recombinantly expressed in Escherichia coli (E. coli), and their effects on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated. Regarding the cell cycle distribution test and 5-ethynyl-2'-deoxyuridine (EdU) assays, arresten and canstatin could repress the proliferation of HUVECs at a range of concentrations. Transwell assay indicated that the migration of HUVECs was significantly decreased in the presence of arresten and canstatin, while tube formation assays suggested that the total tube length and junction number of HUVECs were significantly inhibited by these two proteins; moreover, they could also reduce the expression of vascular endothelial growth factor (VEGF) and the phosphorylation levels of PI3K and Akt, which indicated that the activation of the 3-kinase/serine/threonine-kinase (PI3K/Akt) signaling pathway was inhibited. These findings may have important implications for the soluble recombinant expression of human arresten and canstatin, and for the related therapy of cancer.

Untargeted LC-MS/MS-Based Multi-Informative Molecular Networking for Targeting the Antiproliferative Ingredients in Tetradium ruticarpum Fruit.

The fruit of Tetradium ruticarpum (TR) is commonly used in Chinese herbal medicine and it has known antiproliferative and antitumor activities, which can serve as a good source of functional ingredients. Although some antiproliferative compounds are reported to be present in TR fruit, most studies only focused on a limited range of metabolites. Therefore, in this study, the antiproliferative activity of different extracts of TR fruit was examined, and the potentially antiproliferative compounds were highlighted by applying an untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based multi-informative molecular networking strategy. The results showed that among different extracts of TR fruit, the EtOAc fraction F2-3 possessed the most potent antiproliferative activity against HL-60, T24, and LX-2 human cell lines. Through computational tool-aided structure prediction and integrating various data (sample taxonomy, antiproliferative activity, and compound identity) into a molecular network, a total of 11 indole alkaloids and 47 types of quinolone alkaloids were successfully annotated and visualized into three targeted bioactive molecular families. Within these families, up to 25 types of quinolone alkaloids were found that were previously unreported in TR fruit. Four indole alkaloids and five types of quinolone alkaloids were targeted as potentially antiproliferative compounds in the EtOAc fraction F2-3, and three (evodiamine, dehydroevodiamine, and schinifoline) of these targeted alkaloids can serve as marker compounds of F2-3. Evodiamine was verified to be one of the major antiproliferative compounds, and its structural analogues discovered in the molecular network were found to be promising antitumor agents. These results exemplify the application of an LC-MS/MS-based multi-informative molecular networking strategy in the discovery and annotation of bioactive compounds from complex mixtures of potential functional food ingredients.

First-Principle Derivation of Single-Photon Entropy and Maxwell-Jüttner Velocity Distribution.

This work is devoted to deriving the entropy of a single photon in a beam of light from first principles. Based on the quantum processes of light-matter interaction, we find that, if the light is not in equilibrium, there are two different ways, depending on whether the photon is being added or being removed from the light, of defining the single-photon entropy of this light. However, when the light is in equilibrium at temperature T, the two definitions are equivalent and the photon entropy of this light is hν/T. From first principles, we also re-derive the Jüttner velocity distribution showing that, even without interatomic collisions, two-level atoms will relax to the state satisfying the Maxwell-Jüttner velocity distribution when they are moving in blackbody radiation fields.

Polyketides with Anti-neuroinflammatory Activity from Theissenia cinerea.

Theissenia cinerea 89091602 is a previously reported plant-derived bioactive fungal strain, and the active principles separated from the extracts of its submerged culture were shown to exhibit potent anti-neuroinflammatory activities in both cellular study and animal testing. In a continuation of our previous investigation on the bioactive entities from this fungus, solid state fermentation was performed in an attempt to diversify the bioactive secondary metabolites. In the present study, five previously unreported polyketides, theissenophenol (1), theissenepoxide (2), theissenolactone D (3), theissenone (4), and theissenisochromanone (5), together with the known theissenolactone B (6), theissenolactone C (7), and arthrinone (8), were isolated and characterized through spectroscopic analysis and comparison with the literature data. The configurations of theissenepoxide (2) and theissenisochromanone (5) were further corroborated by single-crystal X-ray diffraction data analysis. Theissenone (4), theissenolactone B (6), theissenolactone C (7), and arthrinone (8) exhibited potent nitric oxide production inhibitory activities in murine brain microglial BV-2 cells with IC50 values of 5.0 ± 1.0, 4.5 ± 0.6, 1.1 ± 0.1, and 3.2 ± 0.3 µM, respectively, without any significant cytotoxic effects.

Natural polyketide 6-pentyl-2H-pyrone-2-one and its synthetic analogues efficiently prevent marine biofouling.

Biofouling is a widespread phenomenon in oceans worldwide. With increasing human development and activities in open and coastal waters, and due to the environmental impact of AF organotins and copper-based paint, the demand for nontoxic antifouling (AF) paints is increasing. Various bioassays for antimicrobial activity, anti-biofilm formation and anti-barnacle settlement were established to evaluate the possibility of using marine natural products as AF agents. A series of natural products, isolated from the marine-derived fungi Trichoderma atroviride and T. reesei, were evaluated for their AF activity. One pyrone-type compound (1) demonstrated significant inhibitory activities toward barnacle cyprid settlement. Furthermore, a series of pyrone analogues (S1-S6) were synthesized, and their bioactivities were evaluated in the established systems. The results showed that compounds S5 and S6 exhibited a broad spectrum of bioactivities, such as anti-barnacle settlement, anti-biofilm formation and antimicrobial activities.

Integrated Omics Strategy Reveals Cyclic Lipopeptides Empedopeptins from Massilia sp. YMA4 and Their Biosynthetic Pathway.

Empedopeptins-eight amino acid cyclic lipopeptides-are calcium-dependent antibiotics that act against Gram-positive bacteria such as Staphylococcus aureus by inhibiting cell wall biosynthesis. However, to date, the biosynthetic mechanism of the empedopeptins has not been well identified. Through comparative genomics and metabolomics analysis, we identified empedopeptin and its new analogs from a marine bacterium, Massilia sp. YMA4. We then unveiled the empedopeptin biosynthetic gene cluster. The core nonribosomal peptide gene null-mutant strains (ΔempC, ΔempD, and ΔempE) could not produce empedopeptin, while dioxygenase gene null-mutant strains (ΔempA and ΔempB) produced several unique empedopeptin analogs. However, the antibiotic activity of ΔempA and ΔempB was significantly reduced compared with the wild-type, demonstrating that the hydroxylated amino acid residues of empedopeptin and its analogs are important to their antibiotic activity. Furthermore, we found seven bacterial strains that could produce empedopeptin-like cyclic lipopeptides using a genome mining approach. In summary, this study demonstrated that an integrated omics strategy can facilitate the discovery of potential bioactive metabolites from microbial sources without further isolation and purification.

Targeted Isolation of Xenicane Diterpenoids from Taiwanese Soft Coral Asterospicularia laurae.

Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins O‒R (1‒4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 µM, respectively.