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Skin wound healing is a complex process involving intricate molecular mechanisms that remain unknown. Restoration of homeostasis after wounding requires the remodeling function of fibroblasts. Here, we demonstrate that phosphorylation of α-cateninS641 was upregulated in fibroblasts upon wounding, which accelerated their proliferation and migration to restore the skin barrier. At the wound edge, phospho-α-cateninS641 stabilized IκBα and thereby impaired expression of NF-κB target genes to promote proliferation and migration of fibroblasts. Mechanically, phospho-α-cateninS641 blocked K48-linked polyubiquitination and proteasomal degradation of IκBα. Moreover, we also demonstrated that EGF/EGFR/CK2α was function as a key upstream signaling of α-catenin by phosphorylating α-catenin at S641. Wound repair was significantly disrupted in skin of mice in which α-catenin phosphorylation and CK2α kinase activity were perturbed in fibroblasts. These findings provide insights into the molecular control of fibroblast proliferation and migration in response to wounding and identify potential targets for the treatment of defective wound repair.

Metabolic engineering 66, 167-178 (2021). doi:10.1016/j.ymben.2021.03.011, Published by Academic Press, Orlando, Fla.

In-silico bitterant prediction received the considerable attention due to the expensive and laborious experimental-screening of the bitterant. In this work, we collect the fully experimental dataset containing 707 bitterants and 592 non-bitterants, which is distinct from the fully or partially hypothetical non-bitterant dataset used in the previous works. Based on this experimental dataset, we harness the consensus votes from the multiple machine-learning methods (e.g., deep learning etc.) combined with the molecular fingerprint to build the bitter/bitterless classification models with five-fold cross-validation, which are further inspected by the Y-randomization test and applicability domain analysis. One of the best consensus models affords the accuracy, precision, specificity, sensitivity, F1-score, and Matthews correlation coefficient (MCC) of 0.929, 0.918, 0.898, 0.954, 0.936, and 0.856 respectively on our test set. For the automatic prediction of bitterant, a graphic program "e-Bitter" is developed for the convenience of users via the simple mouse click. To our best knowledge, it is for the first time to adopt the consensus model for the bitterant prediction and develop the first free stand-alone software for the experimental food scientist.

Two molecular marker systems, start codon targeted (SCoT) and target region amplification polymorphism (TRAP), were used for genetic relationship analysis of 36 Dendrobium species collected from China. Twenty-two selected SCoT primers produced 337 loci, of which 324 (96%) were polymorphic, whereas 13 TRAP primer combinations produced a total of 510 loci, with 500 (97.8%) of them being polymorphic. An average polymorphism information content of 0.953 and 0.983 was detected using the SCoT and TRAP primers, respectively, showing that a high degree of genetic diversity exists among Chinese Dendrobium species. The partition of clusters in the unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis plot based on the SCoT and TRAP markers was similar and clustered the 36 Dendrobium species into four main groups. Our results will provide useful information for resource protection and will also be useful to improve the current Dendrobium breeding programs. Our results also demonstrate that SCoT and TRAP markers are informative and can be used to evaluate genetic relationships between Dendrobium species.

A series of pyrrolopyrazinone-chalcone hybrids(12a–12q) was designed, synthesized and screened for their antitumor activity against SKOV-3, A549 and HeLa cell lines in vitro. Compared with the pyrrolopyrazinone( 10a) and 5-fluorouracil(5-FU), nearly all the tested compounds showed significantly-improved antitumor activities. The most promising compounds 12e and 12k(IC50=0.25 and 0.88 μmol/L) respectively show activities of 123 and 35 times that of compound 10a(IC50=30.74 μmol/L) against HeLa cell line. The result reveals that the presence of chalcone moiety is beneficial to their activity and selectivity.

In the work, a novel multifunctional silica-based nanoplatform (Pd@Ag@SiO2(RITC)-R8) for bioimaging and photothermal therapy (PTT) of cancer cells has been developed. The Pd@Ag nanosheets encapsulated inside silica can act as effective near-infrared (NIR) absorbers for cancer photothermal therapy. Fluorescent dye, rhodamine B isothiocyanate (RITC), was covalently doped into the silica network to provide the capacity for optical imaging. After amine modification, the Pd@Ag@SiO2(RITC)-NH2 can be further conjugated with octaarginine (R8, a cell penetrating peptide) for enhancing the uptake of nanoparticles by cells. Confocal fluorescent images and flow cytometry analysis revealed that R8-conjugated nanoparticles (Pd@Ag@SiO2(RITC)-R8) were taken up by cells more efficiently. Correspondingly, the optical imaging and photothermal therapeutic efficiency of Pd@Ag@SiO2(RITC)-R8 upon cancer cells were also raised due to their higher cellular uptake when compared with that of Pd@Ag@SiO2(RITC)-NH2. Our results indicate that these multifunctional Pd@Ag@SiO2(RITC)-R8 may have great potential for applications in imaging-guided cancer photothermal therapy.

The preparation, characterization and application of NaYF4:Yb3+, Tm3+–NaYF4:Yb3+, Er3+ core–shell upconversion nanocrystals (UCNPs) with multiple emission peaks (e.g. 539, 654 and 802 nm) have been demonstrated in this work. The monodisperse nanocrystals were prepared via a modified thermal decomposition synthesis. The resulting UCNPs were ∼31 nm in diameter with the lanthanide ions Tm3+ and Er3+ doped in the core and the shell, respectively. Under the laser diode excitation at 980 nm, these core–shell nanocrystals give strong upconversion emissions from the visible to near-infrared (NIR) region. By coating a PEG–phospholipid (PP) layer on the surface of the nanocrystals, the as-prepared UCNPs were favorably endowed with good water solubility for the potential biological applications. Here, a photosensitizer drug of Chlorin e6 (Ce6), which has maximum absorption that overlaps with the red emission of UCNPs, was loaded on these PP-coated UCNPs (UCNP@PP) by physical adsorption. The activity of the Ce6-loaded UCNP@PP (UCNP@PP–Ce6) in photodynamic therapy of cancer cells in vitro has been fully investigated in this work. Our results indicated that these multifunctional UCNP@PP–Ce6 nanoparticles have efficient NIR-to-NIR upconversion luminescence and photodynamic therapy capabilities, which could be potentially employed as a theranostic platform for cancer treatment.

Over 359 million tons of plastics were produced worldwide in 2018, with significant growth expected in the near future, resulting in the global challenge of end-of-life management. The recent identification of enzymes that degrade plastics previously considered non-biodegradable opens up opportunities to steer the plastic recycling industry into the realm of biotechnology. Here, we present the sequential conversion of polyethylene terephthalate (PET) into two types of bioplastics: a medium chain-length polyhydroxyalkanoate (PHA) and a novel bio-based poly(amide urethane) (bio-PU). PET films were hydrolyzed by a thermostable polyester hydrolase yielding 100% terephthalate and ethylene glycol. A terephthalate-degrading Pseudomonas was evolved to also metabolize ethylene glycol and subsequently produced PHA. The strain was further modified to secrete hydroxyalkanoyloxy-alkanoates (HAAs), which were used as monomers for the chemo-catalytic synthesis of bio-PU. In short, we present a novel value-chain for PET upcycling, adding technological flexibility to the global challenge of end-of-life management of plastics.Graphical abstract