Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF-κB pathway.

The purpose of this study was to explore the effects of combined lead (Pb) and two types of microplastic (MP) (polyvinyl chloride [PVC] and polyethylene [PE]) exposure on glucose metabolism and investigate the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway in mediating these effects in mice. Adult C57BL/6J mice were randomly divided into four groups: control, Pb (100 mg/L), MPs (containing 10 mg/L PE and PVC), and Pb + MPs, each of which was treated with drinking water. Treatments were conducted for 6 weeks. Co-exposure to Pb + MPs exhibited increase glycosylated serum protein levels, insulin resistance, and damaged glucose tolerance compared with the control mice. Additionally, treatment with Pb + MPs caused more severe damage to hepatocytes than when exposed to them alone concomitantly, exposed to Pb + MPs exhibited improved the levels of interleukin-6, tumor necrosis factor-alpha, and malondialdehyde, but reduced superoxide dismutase, glutathione peroxidase, and catalase assay in livers. Furthermore, they increase the Kelch-like ECH-associated protein 1 (Keap1) and phosphorylated p-NF-κB protein levels but reduced the protein levels of heme oxygenase-1 and Nrf2, as well as increased Keap1 mRNA and Nrf2 mRNA. Co-exposure to Pb + MP impacts glucose metabolism via the Nrf2 /NF-κB pathway.

When polymerization meets coordination-driven self-assembly: metallo-supramolecular polymers based on supramolecular coordination complexes.

Polymers have greatly changed and are still changing the way we live ever since, and the construction of novel polymers as functional materials remains an attractive topic in polymer science and related areas. During the past few years, the marriage of discrete supramolecular coordination complexes (SCCs), including two-dimensional (2D) metallacycles and three-dimensional (3D) metallacages, and polymers gave rise to two novel types of metallo-supramolecular polymers, i.e., metallacycle/metallacage-cored star polymers (MSPs) and metallacycle/metallacage-crosslinked polymer networks (MPNs), which has attracted increasing attention and emerged as an exciting new research direction in polymer chemistry. Attributed to their well-defined and diverse topological architectures as well as the unique dynamic features of metallacycles/metallacages as cores or crosslinks, these novel polymers have shown extensive applications. In this review, aiming at providing a practical guide to this emerging area, the introduction of synthetic strategies towards MSPs and MPNs will be presented. In addition, their wide applications in areas such as functional materials, molecular sieving, drug delivery, bacterial killing and bioimaging are also discussed.

A Two-Dimensional Metallacycle Cross-Linked Switchable Polymer for Fast and Highly Efficient Phosphorylated Peptide Enrichment.

The selective and efficient capture of phosphopeptides is critical for comprehensive and in-depth phosphoproteome analysis. Here we report a new switchable two-dimensional (2D) supramolecular polymer that serves as an ideal platform for the enrichment of phosphopeptides. A well-defined, positively charged metallacycle incorporated into the polymer endows the resultant polymer with a high affinity for phosphopeptides. Importantly, the stimuli-responsive nature of the polymer facilitates switchable binding affinity of phosphopeptides, thus resulting in an excellent performance in phosphopeptide enrichment and separation from model proteins. The polymer has a high enrichment capacity (165 mg/g) and detection sensitivity (2 fmol), high enrichment recovery (88%), excellent specificity, and rapid enrichment and separation properties. Additionally, we have demonstrated the capture of phosphopeptides from the tryptic digest of real biosamples, thus illustrating the potential of this polymeric material in phosphoproteomic studies.

Acid-Activated Motion Switching of DB24C8 between Two Discrete Platinum(II) Metallacycles.

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.

Cross-linked supramolecular polymer gels constructed from discrete multi-pillar[5]arene metallacycles and their multiple stimuli-responsive behavior.

A new family of discrete hexakis-pillar[5]arene metallacycles with different sizes have been successfully prepared via coordination-driven self-assembly, which presented very few successful examples of preparation of discrete multiple pillar[n]arene derivatives. These newly designed hexakis-pillar[5]arene metallacycles were well characterized with one-dimensional (1-D) multinuclear NMR ((1)H and (31) P NMR), two-dimensional (2-D) (1)H-(1)H COSY and NOESY, ESI-TOF-MS, elemental analysis, and PM6 semiempirical molecular orbital methods. Furthermore, the host-guest complexation of such hexakis-pillar[5]arene hosts with a series of different neutral ditopic guests G1-6 were well investigated. Through host-guest interactions of hexakis-pillar[5]arene metallacycles H2 or H3 with the neutral dinitrile guest G5, the cross-linked supramolecular polymers H2⊃(G5)3 or H3⊃(G5)3 were successfully constructed at the high-concentration region, respectively. Interestingly, these cross-linked supramolecular polymers transformed into the stable supramolecular gels upon increasing the concentrations to a relatively high level. More importantly, by taking advantage of the dynamic nature of metal-ligand bonds and host-guest interactions, the reversible multiple stimuli-responsive gel-sol phase transitions of such polymer gels were successfully realized under different stimuli, such as temperature, halide, and competitive guest, etc. The mechanism of such multiple stimuli-responsive processes was well illustrated by in situ multinuclear NMR investigation. This research not only provides a highly efficient approach to the preparation of discrete multiple pillar[n]arene derivatives but also presents a new family of multiple stimuli-responsive "smart" soft matters.

Replication Origin Deletion Enhances Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Synthesis in Haloarchaea.

Although the use of multiple replication origins for chromosome replication has been widely characterized in haloarchaea, whether it is possible to manipulate the chromosome copy number by their genetic engineering is not known, and how it would affect the cell functioning is poorly understood. Here, we demonstrate that deletion of the three active chromosomal origins in Haloferax mediterranei remarkably reduces its DNA amounts and ploidy numbers. Consequently, the mutant strain H. mediterranei Δ123 is more sensitive to UV and mitomycin C. Surprisingly, the cell size increases by 21.2%, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production in shake flask culture enhances from 7.23 to 8.11 g/L in ΔEPSΔ123, although there is also a decrease in cell growth. In this mutant, the chromosomal copy number decreases, whereas the pha-encoding pHM300 megaplasmid copy number increases. Moreover, our transcriptome analysis reveals that the genes involved in primary metabolisms are significantly downregulated in ΔEPSΔ123, whereas those responsible for starch utilization and precursor supplying for PHBV monomers are upregulated. This indicates that more energy and carbon flux is redirected from primary metabolism to PHBV synthesis, thereby enhancing its PHBV accumulation. These findings may therefore provide a rational design to enhance PHBV synthesis by simply tuning the replication origins to modulate the chromosome/megaplasmid copy number ratio and subsequently influence cellular metabolism and physiological functions. IMPORTANCE The haloarchaeon Haloferax mediterranei is a potential producer of PHBV (100% biodegradable plastic) from inexpensive carbon sources. We previously reported that H. mediterranei possessed three active chromosomal origins and, when these origins were deleted, a dormant origin was activated to initiate the replication of chromosome. In this context, in the present study, we first found a close connection between replication initiation and PHBV accumulation. We describe the potential industrial advantages of the strain H. mediterranei ΔEPSΔ123, which includes the enlargement of cell volume by 21.2% and enhancement of PHBV production by 11.2%. We further reveal the possible mechanism that contributes to the greater PHBV production in the ΔEPSΔ123 strain. Overall, we provide here a conceptual advance in the field of synthetic biology by modulating chromosome replication to improve the production of bio-based chemicals.

Microfluidic preparation of PLGA microspheres as cell carriers with sustainable Rapa release.

The current study, inspired by the immunosuppressive property of rapamycin (Rapa) and the benefit of microspheres both as drug delivery system and cell carriers, was designed to develop an efficient Rapa delivery system with tunable controllability to facilitate its local administration. A capillary-based two-phase microfluidic device was designed to prepare monodisperse poly(lactide-co-glycolide) (PLGA) microspheres to load Rapa (PLGA-Rapa-M). The physical and chemical properties of PLGA-Rapa-M were characterized, and the Rapa loading capacity and release profile were explored. Chondrocytes were chosen as a cell model to evaluate the adhesion and proliferation on these microspheres. Controllability over the microsphere properties was illustrated. The PLGA-Rapa-M is averagely 63.91 µm in size with a narrow size distribution and a CV of 2.44%. The encapsulation efficiency of Rapa within microspheres via the current microfluidics was around 98%, and Rapa loading could be easily varied with a maximum value of ∼20%. The PLGA-Rapa-M has a sustained Rapa release duration of ∼3 months. These microspheres could not only successfully be used for Rapa sustained release but also as cell carriers for cell therapy since they can support the attachment/proliferation of chondrocytes. Hence, improved therapeutic index could be expected by using the current developed Rapa-release system.

Materials Stiffness-Dependent Redox Metabolic Reprogramming of Mesenchymal Stem Cells for Secretome-Based Therapeutic Angiogenesis.

Cellular redox metabolism has emerged as a key tenet in stem cell biology that can profoundly influence the paracrine activity and therapeutic efficacy of mesenchymal stem cells (MSCs). Although the use of materials cues to direct the differentiation of MSCs has been widely investigated, little is known regarding the role of materials in the control of redox paracrine signaling in MSCs. Herein, using a series of mechanically tunable fibronectin-conjugated polyacrylamide (FN-PAAm) hydrogel substrates, it is shown that a mechanically compliant microenvironment with native-tissue mimicking stiffness (E = 0.15 kPa) can mechano-regulate the intracellular reactive oxygen species (ROS) level in human adipose-derived MSCs (ADMSCs). The cells reciprocate to the ROS imbalance by co-activating the nuclear factor erythroid 2-related factor 2 and hypoxia-inducible factor 1 alpha stress response signaling pathways to increase the production of vascular endothelial growth factor and basic fibroblast growth factor. Conditioned medium collected from ADMSCs grown on the 0.15 kPa FN-PAAm is found to significantly promote in vitro and ex ovo vascularization events. Collectively, these findings highlight the importance of delineating critical materials properties that can enable the reprogramming of cellular redox signaling for advanced MSCs-based secretome regenerative medicine.

Coordination-driven self-assembly of cavity-cored multiple crown ether derivatives and poly[2]pseudorotaxanes.

The synthesis of a new 120 degree diplatinum(II) acceptor unit and the self-assembly of a series of two-dimensional metallacyclic polypseudorotaxanes that utilize both metal-ligand and crown ether-dialkylammonium noncovalent interactions are described. Judiciously combining complementary diplatinum(II) acceptors with bispyridyl donor building blocks, with an acceptor and/or donor possessing a pendant dibenzo[24]crown-8 (DB24C8) moiety, allows for the formation of three new rhomboidal bis-DB24C8, one new hexagonal tris-DB24C8, and four new hexakis-DB24C8 metallacyclic polygons in quantitative yields. The size and shape of each assembly, as well as the location and stoichiometry of the DB24C8 macrocycle, can be precisely controlled. Each polygon is able to complex two, three, or six dibenzylammonium ions without disrupting the underlying metallacyclic polygons, thus producing eight different poly[2]pseudorotaxanes and demonstrating the utility and scope of this orthogonal self-assembly technique. The assemblies are characterized with one-dimensional multinuclear ((1)H and (31)P) and two-dimensional ((1)H-(1)H COSY and NOESY) NMR spectroscopy as well as mass spectrometry (ESI-MS). Further analysis of the size and shape of each assembly is obtained through molecular force-field simulations. (1)H NMR titration experiments are used to establish thermodynamic binding constants and poly[2]pseudorotaxane/dibenzylammonium stoichiometries. Factors influencing the efficiency of poly[2]pseudorotaxane formation are discussed.

Preparation and in vitro study of hydrochloric norvancomycin encapsulated poly (d,l-lactide-co-glycolide, PLGA) microspheres for potential use in osteomyelitis.

HNV-loaded PLGA microspheres (HNV-PLGA MSs) were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique. The surface of prepared HNV-PLGA MSs is smooth and nonporous with an average diameter of 69.9 µm. The drug-loading rate and encapsulation rate of HNV-PLGA MSs are 4.40 ± 0.26% and 48.51 ± 14.83%, respectively. Additionally, 43.36% of HNV was released from PLGA MSs after seven days of incubation. The antibacterial effects of HNV released from PLGA were as good as the pure HNV. HNV-loaded PLGA microspheres were successfully prepared using double emulsion solvent evaporation technique and their properties met the requirements for local anti-infection.

MUC1 aptamer-based near-infrared fluorescence probes for tumor imaging.

PURPOSE: DNA aptamer (APT) is able to bind to Mucin 1 (MUC1) specifically. The possibility of APT acting as a moiety to construct tumor-targeting probes was investigated. PROCEDURES: A near-infrared (NIR) fluorescent dye (MPA) and polyethylene glycol (PEG) were conjugated to APT to form APT-MPA and APT-PEG-MPA. The successful synthesis of the two probes was characterized via thin layer chromatography (TLC) and optical spectra. The tumor-targeting efficacy of the probes was evaluated in detail at cell level and animal level, respectively. RESULTS: The results indicated that MPA and PEG were successfully coupled with APT. APT-based probes were mediated by Mucin 1 into tumor cells, and PEG-modified probe exhibited higher cell affinity. CONCLUSIONS: The aptamer-based NIR fluorescent probes are promising candidates for tumor imaging and diagnosis.

[Effect of H-uvulopalatopharyngoplasty on endothelium dependent flow-mediated dilation in patients with moderate to severe obstructive sleep apnea syndrome].

OBJECTIVE: This study evaluates the effects of H-uvulopalatopharyngoplasty (H-UPPP) on endothelial function by endothelium dependent flow-mediated dilation(FMD) in patients with moderate to severe obstructive sleep apnea syndrome (OSAHS). METHOD: Forty-five healthy subjects and 49 patients with moderately to severe OSAHS who desired H-UPPP were prospectively enrolled. FMD was measured by high-resolution B-mode ultrasonography. All subjects participated in sleep studies. These studies were repeated 6 months after H-UPPP in patients with moderately to severe OSAHS. RESULT: There was significant difference in FMD between patients with moderately to severe OSAHS and healthy subjects at baseline (6.5 +/- 2.1)% vs (11.2 +/- 3.1)% (P < 0.01). FMD increased from (6.5 +/- 2.1)% to (9.7 +/- 2.7)% 6 months after H-UPPP in patients with moderately to severe OSAHS (P < 0.01). CONCLUSION: FMD is decreased in patients with moderately to severe OSAHS, H-UPPP treatment of these patients leads to improvement of FMD.

Effect of Han-uvulopalatopharyngoplasty on flow-mediated dilatation in patients with moderate or severe obstructive sleep apnea syndrome.

CONCLUSION: Flow-mediated dilatation (FMD) is decreased in patients with moderate or severe obstructive sleep apnea syndrome (OSAS), and Han-uvulopalatopharyngoplasty (H-UPPP) can improve FMD. OBJECTIVE: To evaluate FMD in patients with moderate or severe OSAS and observe the effect of H-UPPP on FMD in these patients. METHODS: Forty-nine patients who were first diagnosed with moderate or severe OSAS by polysomnography (PSG) and had no other diseases served as the experimental group, and 35 individuals with normal PSG as the control group. FMD was measured with high-resolution B-mode ultrasonography in the two groups. PSG and FMD were again performed in the experimental group 6 months after H-UPPP. RESULTS: FMD was significantly lower in the experimental group than in the control group (6.5 ± 2.1% vs 11.2 ± 2.9%, p < 0.01). FMD was significantly improved 6 months after H-UPPP compared with preoperative FMD (9.7 ± 2.7% vs 6.5 ± 2.1%, p < 0.01).

Low-loss electromagnetic composites for RF and microwave applications.

Low-loss electromagnetic composites with high permittivity and permeability will benefit the miniaturization and multifunctional of RF devices. A kind of low-loss dielectric-magnetic ceramic-ceramic composite was developed by hybrid processing technology with the goal of integrating the dielectric properties and magnetic properties. The hybrid processing technology exhibits the advantage of lowered sintering temperatures for the composites while retaining good microstructure and high performance. By introducing elastomer as matrix, a kind of flexible low-loss dielectric-magnetic ceramic-polymer composite was prepared and studied. The obtained flexible dielectric-magnetic ceramic-polymer composite exhibited low loss and good mechanical properties. The results show good effects on lowering the dielectric loss and extending the cut-off magnetic frequency of the electromagnetic composite. Methods for tailoring the properties of the multifunctional composites were proposed and discussed.