Engineered CpG-Loaded Nanorobots Drive Autophagy-Mediated Immunity for TLR9-Positive Cancer Therapy.

Smart nanorobots have emerged as novel drug delivery platforms in nanomedicine, potentially improving anti-cancer efficacy and reducing side effects. In this study, an intelligent tumor microenvironment-responsive nanorobot is developed that effectively delivers CpG payloads to Toll-like receptor 9 (TLR9)-positive tumors to induce autophagy-mediated cell death for immunotherapy. The nanorobots are fabricated by co-self-assembly of two amphiphilic triblock polymer peptides: one containing the matrix metallopeptidase 2 (MMP2)-cleaved GPLGVRGS motif to control the mechanical opening of the nanorobots and provide targeting capability for TLR-9-positive tumors and the other consisting of an arginine-rich GRRRDRGRS sequence that can condense nuclear acid payloads through electrostatic interactions. Using multiple tumor-bearing mouse models, it is investigated whether the intravenous injection of CpG-loaded nanorobots could effectively deliver CpG payloads to TLR-9-positive tumors and elicit anti-tumor immunity through TLR9 signaling and autophagy. Therefore, besides being a commonly used adjuvant for tumor vaccination, CpG-loaded nanorobots can effectively reprogram the tumor immunosuppressive microenvironment and suppress tumor growth and recurrence. This nanorobot-based CpG immunotherapy can be considered a feasible approach to induce anti-tumor immunity, showing great therapeutic potential for the future treatment of TLR9-positive cancers.

Ultrasmall RuM (Mo, W, Cr) Decorated on Nitrogen-doped Carbon Nanosheet with Strong Metal-support Interactions for Electrocatalytic Hydrogen Generation in Wide pH Range.

Developing efficient electrocatalysts for hydrogen evolution reaction (HER) in full pH range can promote the practical applications of hydrogen energy. In this work, nitrogen doped carbon nanosheets supported RuM (Mo, W, Cr) (RuM/NCN) are prepared through an ultrafast microwave approach. The carbon nanosheet structure coupled with the ultrasmall RuM nanoparticles can expose rich active sites to optimize the catalytic activity. Moreover, the strong metal-support interactions also favor to accelerate the reactions kinetics and improve stability. Thus, the developed RuMo/NCN (RuW/NCN) show excellent HER catalytic activities with overpotentials of 72 (75) mV, 82 (82) mV and 124 (119) mV to reach current density of 10 mA cm -2 in 1 M KOH, 0.5 M H2SO4 and alkaline seawater, respectively, and also achieve excellent performance in 1 M PBS. This work provides a valid and novel avenue to design efficient electrocatalysts in renewable energy-related fields.

The clinical progress and challenges of mRNA vaccines.

Owing to the breakthroughs in the prevention and control of the COVID-19 pandemic, messenger RNA (mRNA)-based vaccines have emerged as promising alternatives to conventional vaccine approaches for infectious disease prevention and anticancer treatments. Advantages of mRNA vaccines include flexibility in designing and manipulating antigens of interest, scalability in rapid response to new variants, ability to induce both humoral and cell-mediated immune responses, and ease of industrialization. This review article presents the latest advances and innovations in mRNA-based vaccines and their clinical translations in the prevention and treatment of infectious diseases or cancers. We also highlight various nanoparticle delivery platforms that contribute to their success in clinical translation. Current challenges related to mRNA immunogenicity, stability, and in vivo delivery and the strategies for addressing them are also discussed. Finally, we provide our perspectives on future considerations and opportunities for applying mRNA vaccines to fight against major infectious diseases and cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Bisphenol A adsorption and transport in loess and cationic surfactant/hydrophilic polymer modified bentonite liners.

Bisphenol A (BPA) is a toxic endocrine disruptor often found in landfill leachate. Adsorption behaviors and mechanisms of BPA onto organo-bentonites amended loess, e.g., Hexadecyltrimethylammonium chloride-bentonite (HTMAC-B) and Carboxymethylcellulose-bentonite (CMC-B) were experimentally investigated. The adsorption capacity of loess amended by HTMAC-B (LHB) and CMC-B (LCB) is 4.2 and 4 times greater than that of loess (L), respectively. It is attributed to the increase of hydrogen bonds and hydrophobic lateral interactions between the adsorbent and the adsorbate. The binary (Pb2+-BPA) systems may enhance BPA adsorption onto the samples by the formation of coordination bonds between the hydroxyl group of BPA and Pb2+ ions. A cycled column test was used for investigating the transport behavior of BPA in LHB and LCB samples. The hydraulic conductivity of loess amended by the organo-bentonite (e.g., HTMAC-B, CMC-B) is generally lower than 1 × 10-9 m/s. Especially for CMC-B amended loess, the hydraulic conductivity can be reduced to 1 × 10-12 m/s. This guarantees the hydraulic performance of the liner system. Transport behavior of BPA in cycled column test is explained by the mobile-immobile model (MIM). Modelling results showed that loess amended by organo-bentonites can increase the breakthrough time of BPA. In comparison to loess-based liner, the breakthrough time of BPA for LHB and LCB can be increased by a factor of 10.4 and 7.5, respectively. These results indicate that organo-bentonites can serve as a potentially effective amendment for improving the adsorption of loess-based liners.

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.

Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various advantages for drug delivery, including increased bioavailability, effectiveness, dose-response, targeting capabilities, and safety as compared to traditional drugs. Therefore, nanotechnology to deliver ATO to solid tumors is the main topic of this review, which outlines the previous and present medical applications of ATO. We also summarised ATO anti-cancer mechanisms, limitations, and outcomes of combinatorial treatment with chemo agents. As a result, we strongly recommend conducting pre-clinical and clinical studies of ATO, especially nano-system-based ones that might lead to a novel combination therapy for cancer treatment with high efficacy, bioavailability, and low toxicity for cancer patients.

Assessing and predicting soil carbon density in China using CMIP5 earth system models.

Soil carbon (SC) is a key component of the carbon cycle and plays an important role in climate change; however, quantitatively assessing SC dynamics at the regional scale remains challenging. Earth system model (ESM) that considers multiple environmental factors and spatial heterogeneity has become a powerful tool to explore carbon cycle-climate feedbacks, although the performance of the ESM is diverse and highly uncertain. Thus, identifying reliable ESMs is a prerequisite for better understanding the response of SC dynamics to human activity and climate change. The 16 ESMs that participated in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) were employed to evaluate the skill performance of SC density simulation by comparison with reference data from the International Geosphere-Biosphere Programme Data and Information System (IGBP-DIS). Although ESMs generally reflect spatial patterns with lower SC in northwest China and higher SC in southeast China, 11 of 16 ESMs underestimated the SC in China, and 5 of 16 ESMs overestimated the SC density as most ESMs had large discrepancies in capturing the SC density in the northern high latitudes of China and the Qinghai-Tibet Plateau. According to a series of model performance statistics, SC simulated by Institute Pierre Simon Laplace (IPSL) Coupled Model had a close spatial pattern with IGBP-DIS and showed higher skills for SC predictions in China relative to other CMIP5 ESMs. The multimodel ensemble average obtained by IPSL family ESMs showed that SC density exhibited increasing trends under both the RCP4.5 scenario and RCP8.5 scenario. The SC density increased slowly under RCP8.5 compared with that under RCP4.5 and even displayed a decreasing trend in the late 21st century. The findings of this study can provide a reference for identifying the shortcomings of SC predictions in China and guide SC parameterization improvement in ESMs.