Highly robust supramolecular polymer networks crosslinked by a tiny amount of metallacycles.

Supramolecular polymeric materials have exhibited attractive features such as self-healing, reversibility, and stimuli-responsiveness. However, on account of the weak bonding nature of most noncovalent interactions, it remains a great challenge to construct supramolecular polymeric materials with high robustness. Moreover, high usage of supramolecular units is usually necessary to promote the formation of robust supramolecular polymeric materials, which restrains their applications. Herein, we describe the construction of highly robust supramolecular polymer networks by using only a tiny amount of metallacycles as the supramolecular crosslinkers. A norbornene ring-opening metathesis copolymer with a 120° dipyridine ligand is prepared and self-assembled with a 60° or 120° Pt(II) acceptor to fabricate the metallacycle-crosslinked polymer networks. With only 0.28 mol% or less pendant dipyridine units to form the metallacycle crosslinkers, the mechanical properties of the polymers are significantly enhanced. The tensile strengths, Young's moduli, and toughness of the reinforced polymers reach up to more than 20 MPa, 600 MPa, and 150 MJ/m3, respectively. Controllable destruction and reconstruction of the metallacycle-crosslinked polymer networks are further demonstrated by the sequential addition of tetrabutylammonium bromide and silver triflate, indicative of good stimuli-responsiveness of the networks. These remarkable performances are attributed to the thermodynamically stable, but dynamic metallacycle-based supramolecular coordination complexes that offer strong linkages with good adaptive characteristics.

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme-Induced Proximity Labeling.

Achieving increasingly finely targeted drug delivery to organs, tissues, cells, and even to intracellular biomacromolecules is one of the core goals of nanomedicines. As the delivery destination is refined to cellular and subcellular targets, it is essential to explore the delivery of nanomedicines at the molecular level. However, due to the lack of technical methods, the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date. Here, we develop an enzyme-induced proximity labeling technology in nanoparticles (nano-EPL) for the real-time monitoring of proteins that interact with intracellular nanomedicines. Poly(lactic-co-glycolic acid) nanoparticles coupled with horseradish peroxidase (HRP) were fabricated as a model (HRP(+)-PNPs) to evaluate the molecular mechanism of nano delivery in macrophages. By adding the labeling probe biotin-phenol and the catalytic substrate H2O2 at different time points in cellular delivery, nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles. Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP (+)-PNPs in macrophages over time. Based on dynamic clustering analysis of these proteins, we further discovered that different organelles, including endosomes, lysosomes, the endoplasmic reticulum, and the Golgi apparatus, are involved in delivery with distinct participation timelines. More importantly, the engagement of these organelles differentially affects the drug delivery efficiency, reflecting the spatial-temporal heterogeneity of nano delivery in cells. In summary, these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

Tailoring carboxylatopillar[5]arene-modified magnetic graphene oxide nanocomposites for the efficient removal of cationic dyes.

A carboxylatopillar[5]arene-embellished (CP5) magnetic graphene oxide nanocomposite (MGO@CP5) was smoothly constructed via a mild layer-by-layer method. The morphology, structure, and surface characteristics of this nanocomposite was investigated by field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, zeta potential, and other techniques. Benefiting from a high capture ability for small molecules of CP5 as a supramolecular host molecule, along with a negative surface charge and large surface area of MGO@CP5, this nanocomposite exhibits an ultrafast, efficient adsorption property for representative cationic dyes: methylene blue (MB) and basic fuchsin (BF). The removal efficiency of MB and BF can reach nearly 99% within 3 min, while the maximum adsorption capacity of the two dyes reaches 240 mg g-1 for MB and 132 mg g-1 for BF. Furthermore, owing to excellent magnetic responsiveness from the tight loading of Fe3O4 nanoparticles on graphene oxide, MGO@CP5 could be easily and magnetically separated, regenerated, and reused four times without an evident reduction in the removal efficiency (>95%). Impressively, the adsorption property of MGO@CP5 reveals a strong tolerance to pH changes and ionic strength interference, which renders it a promising adsorbent in the field of water treatment.

SARS-CoV-2 Spike Protein S1 Exposure Increases Susceptibility to Angiotensin II-Induced Hypertension in Rats by Promoting Central Neuroinflammation and Oxidative Stress.

The SARS-CoV-2 spike S1 subunit (S1) can cross the blood-brain barrier and elicit neuroinflammatory response independent of viral infection. Here we examined whether S1 influences blood pressure (BP) and sensitizes the hypertensive response to angiotensin (ANG) II by enhancing neuroinflammation and oxidative stress in hypothalamic paraventricular nucleus (PVN), a key brain cardiovascular regulatory center. Rats received central S1 or vehicle (VEH) injection for 5 days. One week after injection, ANG II or saline (control) was subcutaneously delivered for 2 weeks. S1 injection induced greater increases in BP, PVN neuronal excitation and sympathetic drive in ANG II rats but had no effects in control rats. One week after S1 injection, mRNA for proinflammatory cytokines and oxidative stress marker were higher but mRNA of Nrf2, the master regulator of inducible antioxidant and anti-inflammatory responses, was lower in the PVN in S1-injected rats than in VEH-injected rats. Three weeks after S1 injection, mRNA for proinflammatory cytokines and oxidative stress marker, microglia activation and reactive oxygen species in the PVN were comparable between S1 and VEH treated control rats but were elevated in two groups of ANG II rats. Notably, ANG II-induced elevations in these parameters were exaggerated by S1. Interestingly, ANG II increased PVN Nrf2 mRNA in VEH-treated rats but not in S1-treated rats. These data suggest that S1 exposure has no effect on BP, but post-S1 exposure increases susceptibility to ANG II-induced hypertension by downregulating PVN Nrf2 to promote neuroinflammation and oxidative stress and augment sympathetic excitation.

A study on the antibacterial activity and antimicrobial resistance of pyridinium cationic pillar[5]arene against Staphylococcus aureus and Escherichia coli / Un estudio sobre la actividad antibacteriana y la resistencia antimicrobiana del pilar catiónico de piridinio[5]areno contra Staphylococcus aureus y Escherichia coli

An increasing number of infections caused by multidrug-resistant (MDR) Staphylococcus aureus （S. aureus） and Escherichia coli （E. coli） have severely affected human society. Thus, it is essential to develop an alternative type of antibacterial agents that has a different bacterial resistance mechanism from that of traditional antibiotics. After the synthesis and structural characterization of a cationic pillar[5]arene with pyridinium groups (PP5), the antibacterial and antibiofilm activities as well as its microbial resistance were systematically investigated. In-depth evaluation of biological studies revealed that PP5 was an active antibacterial agent, with surprising antibiofilm formation ability against E. coli and S. aureus. From the results of differential scanning calorimetry and transmission electron microscopy, it was concluded that the microbicidal activity of PP5 was due to the physical disruption of the pathogen’s membrane and the subsequent leakage of cytoplasmic components, which could greatly reduce the rapid generation of resistance. It was presented that the easily available PP5 has high activity to inhibit Gram-positive and Gram-negative bacteria and/or their biofilms with low cytotoxicity. This pillar[5]arene derivative can be used as a good candidate for controlling drug-resistant pathogenic bacterial infections and treating MDR bacteria.(AU)

A study on the antibacterial activity and antimicrobial resistance of pyridinium cationic pillar[5]arene against Staphylococcus aureus and Escherichia coli.

An increasing number of infections caused by multidrug-resistant (MDR) Staphylococcus aureus （S. aureus） and Escherichia coli （E. coli） have severely affected human society. Thus, it is essential to develop an alternative type of antibacterial agents that has a different bacterial resistance mechanism from that of traditional antibiotics. After the synthesis and structural characterization of a cationic pillar[5]arene with pyridinium groups (PP5), the antibacterial and antibiofilm activities as well as its microbial resistance were systematically investigated. In-depth evaluation of biological studies revealed that PP5 was an active antibacterial agent, with surprising antibiofilm formation ability against E. coli and S. aureus. From the results of differential scanning calorimetry and transmission electron microscopy, it was concluded that the microbicidal activity of PP5 was due to the physical disruption of the pathogen's membrane and the subsequent leakage of cytoplasmic components, which could greatly reduce the rapid generation of resistance. It was presented that the easily available PP5 has high activity to inhibit Gram-positive and Gram-negative bacteria and/or their biofilms with low cytotoxicity. This pillar[5]arene derivative can be used as a good candidate for controlling drug-resistant pathogenic bacterial infections and treating MDR bacteria.

Fast and Dynamic Mapping of the Protein Corona on Nanoparticle Surfaces by Photocatalytic Proximity Labeling.

Protein corona broadly affects the delivery of nanomedicines in vivo. Although it has been widely studied by multiple strategies like centrifugal sedimentation, the rapidly forming mechanism and the dynamic structure of the protein corona at the seconds level remains challenging. Here, a photocatalytic proximity labeling technology in nanoparticles (nano-PPL) is developed. By fabricating a "core-shell" nanoparticle co-loaded with chlorin e6 catalyst and biotin-phenol probe, nano-PPL technology is validated for the rapid and precise labeling of corona proteins in situ. Nano-PPL significantly improves the temporal resolution of nano-protein interactions to 5 s duration compared with the classical centrifugation method (>30 s duration). Furthermore, nano-PPL achieves the fast and dynamic mapping of the protein corona on anionic and cationic nanoparticles, respectively. Finally, nano-PPL is deployed to verify the effect of the rapidly formed protein corona on the initial interaction of nanoparticles with cells. These findings highlight a significant methodological advance toward nano-protein interactions in the delivery of nanomedicines in vivo.

Neuroprotective effects of Chrysanthemum morifolium on cerebral ischemia- reperfusion injury contributes to the oxidative stress suppression and related Keap1/Nrf2 pathway.

BACKGROUND: Ischemic stroke, the cause of death and disability worldwide, is closely related to oxidative stress damage. Chrysanthemum has profound antiantioxidant activity. We aimed to verify whether Chrysanthemum morifolium extract (CME) influences brain injury in cerebral ischemia-reperfusion injury (CR/RI) model. METHODS: In vitro, rat hippocampal H19-7 neurons were pretreated with CME, CR/RI was simulated with oxygen glucose deprivation/reoxygenation (OGD/R). The cell viability, apoptosis, lactate dehydrogenase release, reactive oxygen species (ROS) generation, malonaldehyde (MDA) content and superoxide dismutase（SOD） activity were detected. In vivo, middle cerebral artery occlusion (MCAO) model rats were pre-administered with CME, and then behavioral test, triphenyltetrazolium chloride (TTC), hematoxylin-eosin staining (HE), terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), ROS immunofluorescence, MDA and SOD activity were tested. Furthermore, Keap1/Nrf2 signaling of CME in CI/RI was investigated. RESULTS: In OGD/R induced in H19-7 cells, CME increased OGD/R-induced cell viability and reduced cell apoptosis, which was reversed by siNrf2 transfection . In MCAO rats, CME improved the neurological deficits and alleviated brain injury. However, co-treatment with MLK385 counteracted these neuroprotective effects of CME on MCAO rats. CONCLUSION: CME could significantly reduce oxidative stress and nerve injury in vitro and in vivo models of CI/RI by regulating the Keap1/Nrf2 pathway.

Complementary water and nutrient utilization of perianth structural units help maintain long floral lifespan in Dendrobium.

Most orchids have high ornamental value with long-lived flowers. However, the mechanisms by which orchids maintain floral longevity are poorly understood. Here, we hypothesized that floral longevity in Dendrobium is maintained by high resource investment and complementary water and nutrient utilization in different structural units of the perianth. To test this hypothesis, we determined which water- and nutrient-related traits are correlated with flower longevity in 23 Dendrobium species or cultivars, and examined variations of the related traits during flower development of one long-lived cultivar. We found that floral longevity was correlated with dry mass per unit area of perianths and total flower biomass, which indicates that maintaining floral longevity requires increased resource investment. During development of long-lived flowers, labella showed a high capacity for water storage and nutrient reutilization, which could partly remedy high water demand and biomass investment. Sepals and petals, in contrast, had stronger desiccation avoidance and higher metabolic activity with lower biomass investment. These findings indicate that Dendrobium flowers maintain longevity by complementary water and nutrient utilization strategies in the sepals, petals and labella, with labella consuming more water and nutrients to extend flower display, and sepals and petals using a more conservative strategy.

Host-Guest Encapsulation to Promote the Formation of a Multicomponent Trigonal-Prismatic Metallacage.

An inclusion complex of a trigonal-prismatic metallacage with two coronene guests was constructed by multicomponent coordination-driven self-assembly from a 90° platinum(II) acceptor [cis-Pt(PEt3)2(OTf)2], disodium terephthalate, and 2,4,6-tri(4-pyridyl)-1,3,5-triazine in the presence of excess coronene. This platinum(II)-based trigonal prism was found to be a highly matched host to simultaneously encapsulate two coronene molecules. The encapsulation of coronene can effectively promote the formation of a pure single-prismatic metallacage and can stabilize the self-assembled structure via strong π-π-stacking interactions between coronene and the metallacage.

Regulation of Chiral Phosphoric Acid Catalyzed Asymmetric Reaction through Crown Ether Based Host-Guest Chemistry.

Supramolecular asymmetric catalysis has arisen from the in-depth intersection of supramolecular chemistry and asymmetric catalysis due to its unique advantages in building chiral catalyst libraries and regulating performance of catalysts. Herein, we combine crown ether based host-guest chemistry with chiral phosphoric acid mediated asymmetric catalysis to actualize the supramolecular regulation of catalytic asymmetric two-component tandem acetalization reactions. By comparison with the catalytic reaction without host-guest interaction, improvement of up to 72% in yield and increases of up to 13% in enantioselectivity were acquired after addition of the alkali metal guests, which demonstrated the great advantages of this supramolecular regulation strategy.

Clinical independent prognostic factors and overall survival prognostic nomogram for intracranial subependymoma: A SEER population-based analysis 2004-2016.

Purpose: This study was launched to ascertain the independent prognostic factors influencing the overall survival (OS) prognosis of intracranial subependymoma and construct a prognostic model to predict OS time. Materials and methods: We collected data from patients with intracranial subependymoma, including treatment data, follow-up data, and clinical and pathological characteristics from the SEER database within 2004 to 2016, and patients were randomly classified into training and validation cohorts. Univariate and multivariate analyses were applied to the training group through building a Cox proportional hazards model. According to the results of multivariate analysis, we established a nomogram to forecast the OS rate of the per-case patient graphically, then calculated the accuracy of verification in both training and validation cohorts by concordance index (C-index). Univariate and multivariate analyses were used for different subgroups of unoperated versus operated, gross total resection (GTR), subtotal resection (STR), and biopsy after using the propensity score matching (PSM) analyses. Results: A total of 667 patients were enrolled, and we randomly assigned 535 patients (80.21%) into the training cohort and 132 patients (19.79%) into the validation cohort. Age [hazard ratio (HR) = 6.355; 95% confidence interval (CI), 2.240-18.029; p = 0.001] and sex (HR = 0.475; 95% CI, 0.232-0.974; p = 0.042) were the independent prognostic factors in the training cohort. On the basis of age and sex, the nomogram was established to predict the OS for every patient (C-index = 0.733 ± 0.065 in the training cohort and 0.850 ± 0.065 in the validation cohort), and calibration plots reflected the reliability of the nomogram. Age, gender, or laterality was the independent prognostic factor for OS in the different matched subgroups of unoperated versus operated, GTR, STR, and biopsy. Surgical treatment, race, year of diagnosis, insurance, tumor location, tumor size, pathology, tumor grade, and radiation were not statistically significantly different in OS for subependymoma in our research. Conclusion: Age and sex were the independent prognostic variables for OS in intracranial subependymoma. According to our research, we should not be more inclined to choose conservative or surgical treatment. Nonetheless, the information that we present might be useful to suggest potential hypotheses to be tested in the clinical research setting.

Interaction of Neurovascular Signals in the Degraded Condylar Cartilage.

Introduction: Degradation of the condylar cartilage during temporomandibular joint osteoarthritis (TMJ-OA) results in the infiltration of nerves, blood vessels and inflammatory cells from the subchondral bone into the cartilage. The interaction among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA remains largely unknown. Method: In the present study, microarray-based transcriptome analysis was used to detect, and quantitative real-time polymerase chain reaction was used to validate transcriptome changes in the condylar cartilage from a well-established rat TMJ-OA model. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were conducted. Result: There were 1817 differentially expressed genes (DEGs, fold change ≥2, p < 0.05) between TMJ-OA and control cartilages, with 553 up-regulated and 1,264 down-regulated genes. Among those genes, representative DEGs with known/suspected roles in innervation, angiogenesis and inflammation were further validated by enriched GO terms and KEGG pathways. The DEGs related to innervation were predominately enriched in the GO terms of neurogenesis, generation of neurons, and KEGG pathways of cholinergic synapse and neurotrophin signaling. Genes related to angiogenesis were enriched in GO terms of vasculature and blood vessel development, and KEGG pathways of hypoxia-inducible factor 1 (HIF-1) pathway and calcium signaling pathway. For inflammation, the DEGs were enriched in the GO terms of immune system process and immune response, and KEGG pathways of Toll-like receptor and transforming growth factor ß (TGFß) signaling. Analysis with PPI indicated that the aforementioned DEGs were highly-interacted. Several hub genes such as v-akt murine thymoma viral oncogene homolog 1 (Akt1), glycogen synthase kinase 3ß (Gsk3b), fibroblast growth factor 2 (Fgf2) and nerve growth factor receptor (Ngfr) were validated. Conclusion: The present study demonstrated, for the first time, that intimate interactions exist among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA.

Corrigendum: Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis.

[This corrects the article DOI: 10.3389/fcell.2020.529544.].

Clinical prognostic factors for central neurocytoma and subgroup analysis of different treatment measures: A SEER database-based retrospective analysis from 2003 to 2019.

Purpose: The study aimed to identify clinical prognostic factors affecting overall survival (OS) in patients with central neurocytoma (CN) and to determine independent prognostic factors in the subgroups of different treatment modalities using a retrospective analysis based on the SEER database from 2003 to 2019. Materials and methods: Data regarding patients with CN, including basic clinical characteristics, treatment measures, and prognosis follow-up, were extracted from the SEER database. The prognostic variables for all patients were assessed using log-rank test as well as univariate and multivariate analyses based on the Cox proportional hazards model. The same statistical methods were used for analysis in different subgroups of gross total resection (GTR), subtotal resection (STR), no surgery, radiotherapy (RT), and no RT. Results: In total, 413 patients were enrolled in this study. Tumor size, primary site surgery, and RT were independent prognostic factors in all patients with CN. In subgroup analyses, RT was not an independent prognostic factor in patients with GTR. However, sex and race were independent prognostic factors in patients with STR. Additionally, tumor size was an independent prognostic factor in patients who did not undergo surgery. Furthermore, sex and primary site were independent prognostic factors in patients who received RT. Size and primary site surgery were independent prognostic factors in patients without RT. Conclusion: In our study, patients with small tumors or GTR or those who did not receive RT showed a better prognosis. GTR was the preferred treatment for CN. RT was not recommended for patients after GTR. Men and African American showed certain advantages after STR surgery. Tumors with a size of >4 cm were recommended for active treatment. In the RT subgroup, patients with tumors outside the ventricle or women had a poorer prognosis than those with tumors within the ventricle or men, respectively. These findings will help clinicians and patients understand the treatment and prognosis of CN visually and intuitively.

Silicified collagen scaffold induces semaphorin 3A secretion by sensory nerves to improve in-situ bone regeneration.

Sensory nerves promote osteogenesis through the release of neuropeptides. However, the potential application and mechanism in which sensory nerves promote healing of bone defects in the presence of biomaterials remain elusive. The present study identified that new bone formation was more abundantly produced after implantation of silicified collagen scaffolds into defects created in the distal femur of rats. The wound sites were accompanied by extensive nerve innervation and angiogenesis. Sensory nerve dysfunction by capsaicin injection resulted in significant inhibition of silicon-induced osteogenesis in the aforementioned rodent model. Application of extracellular silicon in vitro induced axon outgrowth and increased expression of semaphorin 3 A (Sema3A) and semaphorin 4D (Sema4D) in the dorsal root ganglion (DRG), as detected by the upregulation of signaling molecules. Culture medium derived from silicon-stimulated DRG cells promoted proliferation and differentiation of bone marrow mesenchymal stem cells and endothelial progenitor cells. These effects were inhibited by the use of Sema3A neutralizing antibodies but not by Sema4D neutralizing antibodies. Knockdown of Sema3A in DRG blocked silicon-induced osteogenesis and angiogenesis almost completely in a femoral defect rat model, whereas overexpression of Sema3A promoted the silicon-induced phenomena. Activation of "mechanistic target of rapamycin" (mTOR) pathway and increase of Sema3A production were identified in the DRG of rats that were implanted with silicified collagen scaffolds. These findings support the role of silicon in inducing Sema3A production by sensory nerves, which, in turn, stimulates osteogenesis and angiogenesis. Taken together, silicon has therapeutic potential in orthopedic rehabilitation.

Crown Ether-Derived Chiral BINOL: Enantioselective Michael Addition of Alkenyl Boronic Acids to α,ß-Unsaturated Ketones.

A new class of aza-crown ether-derived chiral BINOL catalysts were designed, synthesized, and applied in the asymmetric Michael addition of alkenylboronic acids to α,ß-unsaturated ketones. It was found that introducing aza-crown ethers to the BINOL catalyst could achieve apparently higher enantioselectivity than a similar BINOL catalyst without aza-crown ethers did, although the host-guest complexation of alkali ions by the aza-crown ethers could not further improve the catalysis effectiveness. Under mediation of the aza-crown ether-derived chiral BINOL and in the presence of a magnesium salt, an array of chiral γ,δ-unsaturated ketones were furnished in good enantioselectivities (81-95% ees).

Self-assembly of chiral BINOL cages via imine condensation.

Condensation of an (S)- or (R)-BINOL-derived dialdehyde and tris(2-aminoethyl)amine produced chiral [2+3] imine cages, which were further reduced to furnish more stable chiral amine cages and applied in the enantioselective recognition of (1R,2R)- and (1S,2S)-1,2-diaminocyclohexane.

Genetic analysis and population structure of wild and cultivated wishbone flower (Torenia fournieri Lind.) lines related to specific floral color.

BACKGROUND: The wishbone flower or Torenia fournieri Lind., an annual from tropical Indochina and southern China, is a popular ornamental plant, and many interspecific (T. fournieri × T. concolor) hybrid lines have been bred for the international market. The cultivated lines show a pattern of genetic similarity that correlates with floral color which informs on future breeding strategies. This study aimed to perform genetic analysis and population structure of cultivated hybrid lines comparing with closely related T. concolor wild populations. METHODS: We applied the retrotransposon based iPBS marker system for genotyping of a total of 136 accessions from 17 lines/populations of Torenia. These included 15 cultivated lines of three series: Duchess (A, B, C); Kauai (D, E, F, G, H, I, J); Little Kiss (K, L, M, N, P) and two wild T. concolor populations (Q and R). PCR products from each individual were applied to estimate the genetic diversity and differentiation between lines/populations. RESULTS: Genotyping results showed a pattern of genetic variation differentiating the 17 lines/populations characterized by their specific floral colors. The final PCoA analysis, phylogenetic tree construction, and Bayesian population structural bar plot all showed a clear subdivision of lines/populations analysed. The 15 cultivated hybrid lines and the wild population Q that collected from a small area showed the lowest genetic variability while the other wild population R which sampled from a larger area had the highest genetic variability. DISCUSSION: The extremely low genetic variability of 15 cultivated lines indicated that individual line has similar reduction in diversity/heterozygosity from a bottleneck event, and each retained a similar (but different from each other) content of the wild genetic diversity. The genetic variance for the two wild T. concolor populations could be due to our varied sampling methods. The two wild populations (Q, R) and the cultivated hybrid lines (I, K, M, N, P) are genetically more closely related, but strong positive correlations presented in cultivated lines A, C, E, M, and N. These results could be used to guide future Torenia breeding. CONCLUSIONS: The genetic variation and population structure found in our study showed that cultivated hybrid lines had similar reduction in diversity/heterozygosity from a bottleneck event and each line retained a similar (but different from each other) content of the wild genetic diversity, especially when strong phenotypic selection of floral color overlaps. Generally, environmental factors could induce transposon activation and generate genetic variability which enabled the acceleration of the evolutionary process of wild Torenia species. Our study revealed that wild Torenia populations sampled from broad geographic region represent stronger species strength with outstanding genetic diversity, but selective breeding targeting a specific floral color decreased such genetic variability.

Antibacterial and Antibiofilm Formation Activities of Pyridinium-Based Cationic Pillar[5]arene Against Pseudomonas aeruginosa.

An omnipresent pathogenic bacterium, Pseudomonas aeruginosa (P. aeruginosa PAO1), is easy to contaminate environmental water or foods, causing daily food spoilage and infections. The biofilm-forming ability and bacterial resistance of P. aeruginosa PAO1 make it difficult to be eradicated by traditional bacteriostatic agents. In this work, we designed and synthesized a pyridinium-based pillar[5]arene (PP5), while trimethylammonium-based pillar[5]arene (TP5) was used as a control compound. After clear characterization, the antibacterial and antibiofilm activities as well as the microbial resistance of TP5 and PP5 against P. aeruginosa PAO1 were extensively examined. It was revealed that PP5 exhibited good inhibition activity with the minimum inhibitory concentration (MIC) of 0.051 mmol/L, while no significant antibacterial and biofilm formation activity for TP5 against P. aeruginosa PAO1 was observed. More importantly, PP5 had negligible antimicrobial resistance even after 18th passages. A transmission electron microscope (TEM) showed that PP5 could physically disrupt the cell membranes, causing the leakage of internal constituents, which is possibly ascribed to the synergistic penetrability and π-π interactions of strain, thus greatly reduced the development of bacterial resistance. Overall, the presented studies indicated that pyridinium moieties could facilitate the cationic pillar[5]arene to generate surprising antibacterial and antibiofilm formation ability against P. aeruginosa PAO1.