Poloxamer 407 modified collagen/ß-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/ß-tricalcium phosphate (ß-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

Tuning Electrocatalytic Activities of Dealloyed Nanoporous Catalysts by Macroscopic Strain Engineering.

It is technically challenging to quantitatively apply strains to tune catalysis because most heterogeneous catalysts are nanoparticles, and lattice strains can only be applied indirectly via core-shell structures or crystal defects. Herein, we report quantitative relations between macroscopic strains and hydrogen evolution reaction (HER) activities of dealloyed nanoporous gold (NPG) by directly applying macroscopic strains upon bulk NPG. It was found that macroscopic compressive strains lead to a decrease, while macroscopic tensile strains improve the HER activity of NPG, which is in line with the d-band center model. The overpotential and onset potential of HER display approximately a linear relation with applied macroscopic strains, revealing an ∼2.9 meV decrease of the binding energy per 0.1% lattice strains from compressive to tensile. The methodology with the high strain sensitivity of electrocatalysis, developed in this study, paves a new way to investigate the insights of strain-dependent electrocatalysis with high precision.

Dual Redox Reaction Sites for Pseudocapacitance Based on Ti and -P Functional Groups of Ti3C2PBrx MXene.

MXenes have extensive applications due to their different properties determined by intrinsic structures and various functional groups. Exploring different functional groups of MXenes leads to improved performance or potential applications. In this work, we prepared new Ti3C2PBrx (x=0.4-0.6) MXene with phosphorus functional groups (-P) through a two-step gas-phase reaction. The acquisition of -P is achieved by replacing bromine functional groups (-Br) of Ti3C2Br2 in the phosphorus vapor. After -Br is replaced with -P, Ti3C2PBrx MXene shows an improved areal capacitance (360 mF cm-2) at 20 mV s-1 compared with Ti3C2Br2 MXene (102 mF cm-2). At a current density of 5 mA cm-2 after 10000 cycles, the capacitance retention of Ti3C2PBrx MXene has not decreased. The pseudocapacitive enhancement mechanism has been discovered based on the dual redox sites of the functional groups -P and Ti.

Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

Improved hydrogen evolution performance of Ni-based nanoporous catalyst with Mo and B co-addition.

The exploration of efficient and stable noble-metal-free electrocatalysts for hydrogen evolution reaction (HER) is of great interest for the development of electrochemical hydrogen production technologies. Herein, nanoporous Ni-based catalyst with Mo and B co-addition (NiMoB) prepared by dealloying is reported as an efficient electrocatalysts for HER. The nanoporous NiMoB achieves an overpotential of 31 mV at 10 mA cm-2, along with exceptional catalytic stability in alkaline electrolyte. Density functional theory (DFT) calculations reveal that the incorporation of Mo and B can synergistically optimize the electronic structure and regulate the adsorption of HER intermediates on the Ni active site, thus accelerating the HER kinetics. This study provides a new perspective for the development of non-precious Ni-based catalysts towards efficient hydrogen energy conversion.

Using tea nanoclusters as ß-lactamase inhibitors to cure multidrug-resistant bacterial pneumonia: A promising therapeutic strategy by Chinese materioherbology.

ß-lactamase, a kind of hydrolase in multi-drug resistant pathogens, can hydrolyze ß-lactam antibiotics and make these kinds of antibiotics invalid. Small-molecular inhibitors about the enzyme and their mechanism are widely investigated but they may result in unavoidable adverse reactions and drug-resistance. Herein, we propose a new therapeutic strategy of Chinese materioherbology, in which herbal medicine or traditional Chinese medicinal herbs can be employed as biological functional materials or refreshed/excited by means of materialogy. Natural tea nanoclusters (TNCs) were extracted from tea to inhibit ß-lactamase. Different from the mechanism of small-molecular inhibitors inhibiting enzymes by binding to the corresponding active sites, the TNCs as a cap cover the protein pocket and create a spatial barrier between the active sites and antibiotics, which was named "capping-pocket" effect. TNCs were combined with amoxicillin sodium (Amo) to treat the methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in mice. This combinatorial therapy remarkably outperforms antibiotic monotherapy in reducing MRSA infections and the associated inflammation in mice. The therapeutic strategy exhibited excellent biosafety, without any side effects, even in piglets. Hence, TNCs have great clinical value in potentiating ß-lactam antibiotic activity for combatting multi-drug resistant pathogen infections and the "pocket capping" effect can guide the design of new enzyme inhibitors in near future.