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Hydrogel as a local drug depot can increase drug concentration at the tumor site. However, conventional drug-loaded hydrogel is typically formed by direct dissolution of drug molecules inside the hydrogel, which usually suffers from limited drug retention and poor tumor penetration. In this study, a nanocomposite hydrogel consisting of oxaliplatin (OXA)-conjugated G5 polyamidoamine (G5-OXA) and oxidized dextran (Dex-CHO) is constructed to improve local drug delivery. The OXA-containing nanocomposite hydrogel (denoted as PDO gel) is injectable and could maintain in vivo up to more than three weeks, which increases drug retention in tumor tissues. More interestingly, G5-OXA released from the PDO gel show potent tumor penetration mainly through an active transcytosis process. In vivo antitumor studies in an orthotopic 4T1 tumor model show that PDO gel significantly inhibits primary tumor growth as well as the metastasis. In addition, the PDO gel can also activate the immunosuppressive tumor microenvironment through immunogenic cell death effect, and further improves therapeutic efficacy with the combination of PD-1 antibody. These results demonstrate that the nanocomposite hydrogel can simultaneously enhance the retention and penetration of chemotherapeutic drugs via the combination of both advantages of hydrogel and nanoparticles, which provides new insights for the design of local drug delivery systems. Hydrogel represents an important class of local drug delivery depot. However, conventional drug-loaded hydrogel is usually achieved by direct dissolution of small drug molecules inside the hydrogel, which typically suffers from limited drug retention and poor tumor penetration. Herein, we developed a nanocomposite hydrogel, which could gradually degrade and release drug-conjugated small nanoparticles (∼ 6 nm) for improved tumor penetration through the combination of an active transcytosis process and a passive diffusion process. This nanocomposite hydrogel system improved tumor penetration and retention of drug in primary tumors as well as the drug deposition in lymph nodes, which significantly suppressed tumor growth and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Ammonia borane (AB) is considered to be a promising solid hydrogen carrier. In this work, poly(N-vinyl-2-pyrrolidone) (PVP)-protected platinum nanoparticles are supported on γ-methacryloxypropyltrimethoxysilane (γ-MPS) modified silica spheres (Pt-PVP/SiO 2 (M)), which are firstly used as highly efficient catalysts for hydrolysis of AB. Platinum nanoparticles possess a tiny size of 2–3 nm and are uniformly dispersed over modified silica spheres. Pt-PVP/SiO 2 (M) catalysts with a Pt loading amount of 1.30 wt% show the highest catalytic activity with a turnover frequency (TOF) value of 371 mol H2 mol Pt −1 min−1 (866 mol H2 mol Pt −1 min−1 corrected for the surface atoms) at 25 °C. The activation energy is calculated to be 46.2 kJ/mol. Furthermore, owing to the synergistic effect between the modifier of silica spheres and the capping agent of metal nanoparticles, Pt-PVP/SiO 2 (M) catalysts have a higher loading amount (8.7 and 6.5 times) and TOF value (4.8 and 5.5 times) than the counterparts prepared without γ-MPS and PVP, respectively. [Display omitted] • PVP-protected Pt nanoparticles were uniformly dispersed on modified SiO 2 spheres. • This catalyst showed superior catalytic activity for hydrolysis of ammonia borane. • The highest TOF value of 371 mol H 2 mol Pt−1 min−1 at 25 °C was achieved. • The synergistic effect between the PVP and the modifier of silica was studied. [ABSTRACT FROM AUTHOR]

General ankle-foot orthosis (AFO) cannot be flexibly adjusted to volumetric change in the lower leg because the molding is custom-fit. Thus, we developed a flexible assistive device called elastic neutral AFO (EN-AFO) to help stroke patients hold a neutral ankle position. The purpose of this study was to investigate the effects of EN-AFO and improve gait patterns in stroke patients with rearfoot varus deformity. Fifteen stroke patients with a varus deformity of the foot performed a walking test with and without the use of EN-AFO. Kinematic data were measured with a 3D motion analysis system with inertial measurement unit (IMU) sensors. In the stance phase, maximal pelvic tilt and maximal ankle dorsiflexion in the affected side changed, and maximal and minimal pelvic tilts and maximal hip abduction in the less-affected limb effectively changed, as well. During the swing phase, minimal pelvic tilt and minimal ankle abduction in the affective limb greatly changed; particularly, the reduction of maximal ankle inversion was significantly cleared. The EN-AFO was effective in controlling the tendency of foot inversion in patients with varus deformities. This is suitable for gait training, as it can adjust the orthosis stiffness according to the foot condition. [ABSTRACT FROM AUTHOR]

Cavitation erosion, corrosion and synergism behaviors of HVOF sprayed WC-25WB-10Co-5NiCr and MoB-25NiCr coatings were investigated in this study. Conventional WC-10Co-4Cr and Cr 3 C 2 -25NiCr coatings were also characterized for comparison purposes. The cavitation erosion and cavitation-corrosion experiments were carried out in deionized water and 3.5 wt% NaCl solution respectively. The average mass loss rate was defined to assess the destruction of the coating surface. The cavitation erosion resistance and the cavitation-corrosion resistance were adopted to quantitatively analyze the difference of cavitation erosion and cavitation-corrosion performance of the coatings. The potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) tests were employed to evaluate the corrosion resistance of all the coatings. In addition, the equivalent circuit models were designed to fit the EIS. The cumulative mass loss of all the coatings was measured under the conditions of pure cavitation erosion, pure corrosion and cavitation-corrosion. The total mass loss rate, pure cavitation rate, pure corrosion rate as well as synergistic mass loss rate were calculated to discuss their relative contributions responsible for the material removal. The cavitation-corrosion mechanisms were also discussed by analyzing the eroded surface for all the coatings. [ABSTRACT FROM AUTHOR]

Effective antitumor activity of chemotherapy can be counterbalanced by efferocytosis by generating immunosuppressive tumor microenvironment. Targeted blocking efferocytosis at an early stage of cell apoptosis exerts promising benefits on achieving improved chemotherapy, but it appears to have considerably limited outcome due to the uncontrolled release of chemotherapeutic and efferocytosis inhibitors. Herein, a mesoporous silica nanoparticle (MSN)-based nanoconfined assembly strategy is created to co-deliver chemotherapeutic drug doxorubicin (DOX) and efferocytosis inhibitor BMS777607 (BMS) for efficient cancer chemo-immunotherapy. DOX and BMS self-assembly forms nanoparticulate crystal confined within the mesopore of tailor-made MSN, and nanocrystal-encapsulated MSN (denoted as SC-MSN@D/B) enables synchronized drug release behaviors, which is beneficial for efferocytosis blockade at the early stage of apoptosis. Consequently, intravenous injection of SC-MSN@D/B leads to a synergistic inhibition of tumor growth in colon and breast cancer models through inducing a stimulatory immune response, from the secretion of pro-inflammatory cytokines to the inhibition of tumor associated macrophages and regulatory T cells infiltration. The combination of SC-MSN@D/B with checkpoint blockade inhibitors further amplifies the therapeutic effect of on tumor growth and pulmonary metastasis of orthotopic 4T1 breast tumors, and establishes long-term immune memory, offering tremendous potential for a combined efferocytosis-blocking strategy in cancer chemo-immunotherapy. [Display omitted] • The combination of BMS and DOX elicited a synergistic antitumor effect. • Confined assembly of DOX and BMS was observed in the nanopores of a tailored-made mesoporous silica nanoparticle (MSN). • SC-MSN@D/B effectively blocked the efferocytosis and improved cancer chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • The r-/K-selection theory was applied to anaerobic digestion with sulfate reduction. • The rapid-filling mode enabled reactors to exhibit a fast reaction rate. • The operational mode altered the ethanol metabolic pathway. • The effect of operational mode on bioreactors depended on types of organic carbon. • R-strategists Desulfomicrobium and K-strategists Geobacter were enriched. Anaerobic digestion (AD) is promising for treating high-strength wastewater. However, the effect of operational parameters on microbial communities of AD with sulfate is not yet fully understood. To explore this, four reactors were operated under rapid- and slow-filling modes with different organic carbons. Reactors in the rapid-filling mode generally exhibited a fast kinetic property. For example, the degradation of ethanol was 4.6 times faster in ASBR ER than in ASBR ES , and the degradation of acetate was 11.2 times faster in ASBR AR than in ASBR AS. Nevertheless, reactors in the slow-filling mode could mitigate propionate accumulation when using ethanol as organic carbon. Taxonomic and functional analysis further supported that rapid- and slow-filling modes were suitable for the growth of r-strategists (e.g., Desulfomicrobium) and K-strategists (e.g., Geobacter), respectively. Overall, this study provides valuable insights into microbial interactions of AD processes with sulfate through the application of the r/K selection theory. [ABSTRACT FROM AUTHOR]

The insufficient infiltration of T cells in solid tumors hinders the therapeutic efficacy of immune checkpoint blockade (ICB) antibodies and chimeric antigen receptor (CAR)-T cells. Promoting T or CAR-T cells to efficiently and specifically migrate into solid tumors is critical for improving current immunotherapies, which remains a challenge. Herein, we proposed a CRISPR-based transcriptional activation (CRISPRa) nanomedicine for mobilizing tumor cells to recruit T cells by activating the expression of T cell chemokines CXC-chemokine ligand (CXCL) 9, CXCL10, and CXCL11. We demonstrated that the CRISPRa nanomedicine could dramatically upregulate the expression of these T cell chemokines in tumor cells, thereby facilitating T cell migration directionally into solid tumors. Intratumoral injection of the CRISPRa nanomedicine inhibited the growth of different solid tumors including melanoma, pancreatic, colonic, and breast cancers. Moreover, tumor-specific versions of the CRISPRa nanomedicine possessing the ability to upregulate the T cell chemokine expression only in tumors rather than normal tissues or cells were constructed. Systemic injection of the tumor-specific CRISPRa nanomedicine specifically recruited T or CAR-T cells into solid tumors and improved the therapeutic effects of ICB antibodies (anti-PD-L1 or anti-CTLA4) and CAR-T cells. Thus, the gene-activating nanomedicine provides a promising strategy for enhancing T cell infiltration to improve current immunotherapies against solid tumors. [Display omitted] • CRISPRa nanomedicine recruited effector T cells into tumors via activating T cell chemokines. • Tumor-specific CRISPRa nanomedicine could activate only tumors rather than normal organs to express T cell chemokines. • Systemic injection of the tumor-specific CRISPRa nanomedicine enhanced the efficacy of ICB antibodies and CAR-T cells. [ABSTRACT FROM AUTHOR]