Efficient Delivery of Lomitapide using Hybrid Membrane-Coated Tetrahedral DNA Nanostructures for Glioblastoma Therapy.

Glioblastoma (GBM) is the most aggressive and prevalent primary malignant tumor of the central nervous system. Traditional chemotherapy has poor therapeutic effects and significant side effects due to drug resistance, the natural blood-brain barrier (BBB), and nonspecific distribution, leading to a lack of clinically effective therapeutic drugs. Here, 1430 small molecule compounds are screened based on a high-throughput drug screening platform and a novel anti-GBM drug, lomitapide (LMP) is obtained. Furthermore, a bionic nanodrug delivery system (RFA NPs) actively targeting GBM is constructed, which mainly consists of tetrahedral DNA nanocages (tFNA NPs) loaded with LMP as the core and a folate-modified erythrocyte-cancer cell-macrophage hybrid membrane (FRUR) as the shell. FRUR camouflage conferred unique features on tFNA NPs, including excellent biocompatibility, improved pharmacokinetic profile, efficient BBB permeability, and tumor targeting ability. The results show that the LMP RFA NPs exhibited superior and specific anti-GBM activities, reduced off-target drug delivery, prolonged lifespan, and has negligible side effects in tumor-bearing mice. This study combines high-throughput drug screening with biomimetic nanodrug delivery system technology to provide a theoretical and practical basis for drug development and the optimization of clinical treatment strategies for GBM treatment.

Evaluating the oxidation inhibition of sulfide in urban sewers using a novel quantitative method.

Sulfide inhibition is a critical task for the secure operation of sewer systems, and oxidation is usually utilised to achieve this purpose. However, the effects and mechanism of oxidation during the transformation of sulfur-associated pollutants in gas-liquid-solid phases of sewers have not been extensively evaluated. In this study, a method for quantifying sulfur-associated pollutant exchange pathways in gas-liquid-solid phases of sewers was established. The results showed that although the concentration of sulfide decreased under different oxidation conditions, the consumption of sulfate in sewers clearly increased. The transformation strength of elemental sulfur was high (18.65 mg/L, 35.52% of sulfate from the influent) and the accumulation of sulfate in sediment was obvious (3.49 mg/L, 6.65% of sulfate from the influent). Higher concentrations of sulfate in the influent promoted the generation of sulfide in sediment (8.98 mg/L, 17.10%). Thus, the oxidation process led to the generation of more absolute sulfide. In addition, promoting the metabolism of sulfate-reducing bacteria enhanced the loss of organic carbon in sewers, which might weaken the efficacy of nitrogen and phosphorus removal in wastewater treatment plants. Based on the evaluation of the exchange pathways of sulfur-associated pollutants in sewers, further studies into sulfide inhibition in sewers should consider the above issues to enhance the safe management of urban sewers.

New protocol for the R134a cryogen spray cooling assisted 1064-nm laser lipolysis.

Laser lipolysis is a promising body contouring technology. However, the skin tissue could be thermally damaged owing to the laser energy absorption by water, which limits the lipolysis efficiency. To protect skin tissue and improve the lipolysis effect, cryogen spray cooling is introduced and synergized with the pulsed laser irradiation aiming to propose a new therapy protocol. By simulating heat conduction in the skin after spray cooling assisted laser lipolysis, the temperature distribution in the skin tissue was obtained to analyze the tissue damage by the Arrhenius integral. After parameter optimization according to the damage threshold of skin and adipose tissue, a new protocol with high laser intensity and short time was proposed including 150-ms R134a spray cooling with spray distance of 30 mm, and 100 ms 1064 nm laser irradiation with energy density of 20 J/cm2, with a relaxation for 9.75 s. This cycle of 10 s can be repeated 90 to 150 times for a total of 15 to 25 min. Compared with previous treatment procedure, new protocol can increase the fat dissolution depth from 2 to 4.5 mm beneath the dermis with same order laser fluence.

Light transmittance dynamics and spectral absorption characteristics during auxiliary cryogen spray cooling in laser dermatology.

Cryogen spray cooling (CSC) is widely applied in laser dermatologic surgery to minimize the risk of non-specific epidermal thermal damage caused by the competitive laser energy absorption of epidermal melanin. However, the light absorption and attenuation by cryogen film and subsequent frost formation on the skin surface during CSC are needed to be investigated by using R-134a, R-404A, and R-32. A spray system equipped with an integrating sphere-based light collection apparatus was constructed to evaluate the time-resolved laser transmittance and spectral absorption characteristics induced by R-134a, R-404A, and R-32 sprays, under the clinical-used 755-nm and 1064-nm laser irradiations. No obvious light absorption peaks exist in the wavelengths of 370-1400 nm. R-404A produces the largest average light absorbance (0.089), as compared to those of R-134a (0.066) and R-32 (0.068) in the near-infrared range (780-1400 nm). Given the lowest boiling point and highest latent heat of R-32, the evaporation of liquid film and melting of subsequent frost are promoted, leading to smallest light attenuation. R-32 spray shows great potential in clinics owing to its high light transmittance, small light absorption, and high cooling capability. For R-32 spray, the durations between spurt termination and laser irradiation are recommended to be 8-100 ms and 13-100 ms with average light transmittances of 86% and 95% under 755-nm and 1064-nm laser irradiations.

Efficacy evaluation and treatment parameter optimization for laser surgery of Ota's nevus based on an advanced non-equilibrium bio-tissue heat transfer model.

This study was performed to better understand the laser-tissue interaction mechanism and optimize the laser wavelength and pulse duration for the laser treatment of Ota's nevus, thereby providing the precise theoretical guidance for clinician to improve the therapeutic effect. A non-equilibrium bio-tissue heat transfer model coupled with thermo-mechanical effect for the explosive vaporization of melanin granule induced by laser heating was developed to investigate the temperature and thermal damage distribution using alexandrite (755 nm) and Nd:YAG (1064 nm) lasers with the pulse width of 10-120 ns. Cryogen spray cooling (CSC) was introduced to prevent the epidermal thermal damage due to competitive laser absorption between epidermal and dermal melanin. Thermal injury of the epidermis with temperature in the melanin zone reaching 132.3 °C was induced by alexandrite laser. The optimal pulse durations were 50 and 30 ns, and the corresponding incident laser fluence thresholds were 6.45 and 19.5 J·cm-2 for alexandrite and Nd:YAG laser, respectively, with the pre-cooling of R32 spray. Using R32 spray cooling, the 1064-nm laser fluence threshold of melanin can be increased by 56.0%, resulting in an indirect increase (80.4%) of injury thickness. Nd:YAG laser (1064 nm) was highly suitable for the removal of melanin in the deep tissue owing to its deep penetration. Too short pulse duration should be avoided to prevent the epidermal thermal damage. The improvement of therapeutic effect by CSC demonstrates its high clinical application potential.

Symbiosis of sulfate-reducing bacteria and methanogenic archaea in sewer systems.

Sulfide and methane emissions always simultaneously exist in natural environment and constitute a major topic of societal concern. However, the metabolic environments between sulfate-reducing bacteria (SRB) and methanogenic archaea (MA) exist a great difference, which seems to be opposite to the coexisting phenomenon. To explore this issue, the comprehensive biofilm structures, substrate consuming and metabolism pathways of SRB and MA were investigated in a case study of urban sewers. The results showed that, due to the stricter environmental requirements of MA than SRB, SRB became the preponderant microorganism which promoted the rapid generation of sulfide in the initial period of biofilm formation. According to a metagenomic analysis, the SRB appeared to be more preferential than MA in sewers, and the preponderant SRB could provide a key medium (Methyl-coenzyme M) for methane metabolism. Therefore, the diversity of MA gradually increased, and the symbiosis system formed preliminarily. In addition, via L-cysteine, methane metabolism also participated in sulfide consumption which was involved in cysteine and methionine metabolism. This phenomenon of sulfide consumption led to the forward reaction of sulfide metabolism, which could promote sulfide generation while stabilizing the pH value (H+ concentration) and S2- concentrations which should have inhibited SRB and MA production. Therefore, the heavily intertwined interactions between sulfide and methane metabolism provided environmental security for SRB and MA, and completely formed the symbiosis between SRB and MA. Based on these findings, an ecological model involving synergistic mechanism between sulfide and methane generation is proposed and this model can also improve understanding on the symbiosis of SRB and MA in the natural environment.