Biomimetic Hemostatic Powder Derived from Coacervate-Immobilized Thermogelling Copolymers.

Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol-gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications.

Comparison of the Biochemical Properties and Roles in the Xyloglucan-Rich Biomass Degradation of a GH74 Xyloglucanase and Its CBM-Deleted Variant from Thielavia terrestris.

Xyloglucan is closely associated with cellulose and still retained with some modification in pretreated lignocellulose; however, its influence on lignocellulose biodegradation is less understood. TtGH74 from Thielavia terrestris displayed much higher catalytic activity than previously characterized fungal GH74 xyloglucanases. The carbohydrate-binding module 1 (CBM1) deleted variant (TtGH74ΔCBM) had the same optimum temperature and pH but an elevated thermostability. TtGH74 displayed a high binding affinity on xyloglucan and cellulose, while TtGH74ΔCBM completely lost the adsorption capability on cellulose. Their hydrolysis action alone or in combination with other glycoside hydrolases on the free xyloglucan, xyloglucan-coated phosphoric acid-swollen cellulose or pretreated corn bran and apple pomace was compared. CBM1 might not be essential for the hydrolysis of free xyloglucan but still effective for the associated xyloglucan to an extent. TtGH74 alone or synergistically acting with the CBH1/EG1 mixture was more effective in the hydrolysis of xyloglucan in corn bran, while TtGH74ΔCBM showed relatively higher catalytic activity on apple pomace, indicating that the role and significance of CBM1 are substrate-specific. The degrees of synergy for TtGH74 or TtGH74ΔCBM with the CBH1/EG1 mixture reached 1.22-2.02. The addition of GH10 xylanase in TtGH74 or the TtGH74ΔCBM/CBH1/EG1 mixture further improved the overall hydrolysis efficiency, and the degrees of synergy were up to 1.50-2.16.

Polypeptide Nanoparticles with pH-Sheddable PEGylation for Improved Drug Delivery.

The variation of tumor microenvironments provides a tool for the construction of stimulus-responsive nanomedicines to enhance drug delivery efficacy. Herein, the assembly of drug-loaded polypeptide nanoparticles (NPs) with pH-sheddable modification of poly(ethylene glycol) (PEG) is prepared to enhance therapeutic efficiency. Poly(l-lysine) and poly(l-glutamic acid) were self-assembled to fabricate polypeptide NPs by electrostatic interactions, followed by PEGylation based on amidation reaction. The NP sizes can be controlled by tuning the molecular weight or the ratio of polypeptides. The PEG coating is cleavable at the tumor acid microenvironment to reverse the surface charge and reduce the NP size, which effectively enhances cell uptake. In addition, the presence of reducing reagent (e.g., glutathione) in cancer cells induces the drug (i.e., cisplatin) release from the polypeptide NPs and subsequently results in the cell toxicity. This reported method highlights the engineering of transformable polypeptide drug carriers, which provides a promising way for enhanced drug delivery efficacy.

A novel cellulolytic/xylanolytic SbAA14 from Sordaria brevicollis with a branched chain preference and its synergistic effects with glycoside hydrolases on lignocellulose.

In this study, the novel auxiliary activity (AA) family 14 lytic polysaccharide monooxygenase (LPMO) SbAA14 from Sordaria brevicollis was successfully characterized. It was active against heteroxylan, xyloglucan and cellulose in ß-cellulose and released native oligosaccharides and corresponding C1- and/or C4-oxidized products. SbAA14 showed a branched chain preference, because partial removal of arabinosyl substituents from heteroxylan led to a decrease in activity. SbAA14 had synergistic effects with the debranching enzyme EpABF62C in an enzyme- and ascorbic acid-dependent manner. SbAA14 had synergistic effects with the GH10 endoxylanase EpXYN1, and the degree of synergy was greater with step-by-step addition than with simultaneous addition. SbAA14 could also synergize with Celluclast® 1.5 L on NaOH-pretreated wheat straw and on NaOH-pretreated and hydrogen peroxide-acetic acid (HPAC)-H2SO4-pretreated bamboo substrates. The greatest synergistic effect between SbAA14 and Celluclast® 1.5 L was observed for HPAC-H2SO4-200 mM pretreated bamboo, in which the degree of synergy reached approximately 1.61. The distinctive substrate preference of SbAA14 indicated that it is a novel AA14 LPMO that may act mainly on heteroxylan with numerous arabinosyl substituents between cellulose fibers rather than on recalcitrant xylan tightly associated with cellulose. These findings broaden the understanding of enigmatic AA14 LPMOs and provide new insights into the substrate specificities and biological functionalities of AA14 LPMOs in fungi.

Sticktight-inspired PEGylation for low-fouling coatings.

Polyethylene glycol (PEG) has been widely used for modifying surfaces to reduce non-specific interactions with biomolecules, microorganisms, and cells. Herein, we report a sticktight-inspired PEGylation strategy to fabricate low-fouling coatings. The influence of PEG molecular architectures on the PEG density and biological adhesion were studied. Notably, an increase in the number of arms resulted in improved surface PEGylation and an improved antifouling ability against the adhesion of proteins, mammalian cells and bacteria. The molecular architecture-dependent PEGylation strategy is an attractive approach for developing advanced low-fouling coatings.

Confined microemulsion sono-polymerization of poly(ethylene glycol) nanoparticles for targeted delivery.

Confined sono-polymerization is developed to prepare poly(ethylene glycol) nanoparticles within water-in-oil microemulsion, followed by post-functionalization with a bispecific antibody (anti HER2 and anti PEG) for targeted delivery of photosensitizers (i.e., indocyanine green). The nanoparticles could specifically target to breast cancer cells (i.e., SKBR3) that overexpress HER2 receptors for the inhibition of cancer cell growth under 808 nm laser irradiation. This study highlights a facile and controllable method to fabricate therapeutic nanoparticles capable of targeted delivery.

Poly(ethylene glycol)-Mediated Assembly of Vaccine Particles to Improve Stability and Immunogenicity.

We report the one-step assembly of vaccine particles by encapsulating ovalbumin (OVA) and cytosine-phosphate-guanine oligodeoxynucleotides (CpG) into poly(ethylene glycol) (PEG)-mediated zeolitic imidazolate framework-8 nanoparticles (OVA-CpG@ZIF-8 NPs), where PEG improves the stability and dispersity of ZIF-8 NPs and the NPs protect the encapsulated OVA and CpG to circumvent the cold chain issue. Compared with free OVA and OVA-encapsulated ZIF-8 (OVA@ZIF-8) NPs, OVA-CpG@ZIF-8 NPs can enhance antigen uptake, cross-presentation, dendritic cell (DC) maturation, production of specific antibody and cytokines, and CD4+ T and CD8+ T cell activation. More importantly, the vaccine particles retain their bioactivity against enzymatic degradation, elevated temperatures, and long-term storage at ambient temperature. The study highlights the importance of PEG-mediated ZIF-8 NPs as a vaccine delivery system for the promising application of effective and cold chain-independent vaccination against diseases.

Electron mediators accelerate the microbiologically influenced corrosion of 304 stainless steel by the Desulfovibrio vulgaris biofilm.

In the microbiologically influenced corrosion (MIC) caused by sulfate reducing bacteria (SRB), iron oxidation happens outside sessile cells while the utilization of the electrons released by the oxidation process for sulfate reduction occurs in the SRB cytoplasm. Thus, cross-cell wall electron transfer is needed. It can only be achieved by electrogenic biofilms. This work hypothesized that the electron transfer is a bottleneck in MIC by SRB. To prove this, MIC tests were carried out using 304 stainless steel coupons covered with the Desulfovibrio vulgaris (ATCC 7757) biofilm in the ATCC 1249 medium. It was found that both riboflavin and flavin adenine dinucleotide (FAD), two common electron mediators that enhance electron transfer, accelerated pitting corrosion and weight loss on the coupons when 10ppm (w/w) of either of them was added to the culture medium in 7-day anaerobic lab tests. This finding has important implications in MIC forensics and biofilm synergy in MIC that causes billions of dollars of damages to the US industry each year.

Top-orthogonal-to-bottom-electrode (TOBE) CMUT arrays for 3-D ultrasound imaging.

Two-dimensional ultrasound arrays hold great promise for 3-D imaging; however, wiring of each channel becomes impractical for large arrays or for small-footprint catheter probes for which the number of wires must be limited. Capacitive micromachined ultrasound transducers offer a promising solution for such 2-D array applications, but channel routing is still non-trivial. A top-orthogonal-to-bottom-electrode (TOBE) 2-D CMUT array architecture is presented along with row-column addressing schemes for low-channel-count 3-D ultrasound imaging. An N × N TOBE array is capable of obtaining 3-D images using only 2N channels. An interfacing scheme is presented in which transmit-receive signals are routed along rows while bias voltages are applied along columns, effectively allowing for single-element transmit/receive control. Simulations demonstrated potentially finer resolution and improved side lobe suppression over a previously published row-column-based imaging method. Laser vibrometer testing was done to measure membrane displacement in air and confirmed that single-element air-coupled actuation in transmit mode could be achieved using our proposed interfacing scheme. Acoustic testing was also performed in both transmit and receive modes to characterize the ability of the proposed interfacing scheme to achieve dominant-element transmission and reception in immersion operation. It was seen that membrane displacement in both modes was indeed largely confined to the active area.