Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.

Facile fabrication of a low-cost and environmentally friendly inorganic-organic composite membrane for aquatic dye removal.

This study reports a new inorganic-organic composite membrane fabricated by an electrostatic self-assembling method. The low-cost and eco-friendly porous geopolymer (PG) was chosen as a support, on which chitosan (CS), a "green" biomaterial, was used to form an active layer. With optimum dosage of CS (2.0 mL of 1.0% CS solution), the obtained CS/PG membrane exhibited a high porosity of 50.97% with an average pore diameter of 13.93 nm as well as a high water flux of 1663.82 ± 22.46 L/m2·h·bar. The effects of initial concentration, pH, flow rate and temperature of the feed solution on crystal violet (CV) removal by the CS/PG were evaluated in a continuous mode. The results indicated ~95% CV could be removed from water during continuous treating of 14 h. The effectiveness in CV removal by the CS/PG membrane was attributed to the synergistic effect of rejection and adsorption. Furthermore, the composite membrane could be easily regenerated for prolonged use. Overall, this work opens a new possibility of building cost-saving and eco-friendly composite membranes for practical applications in water purification.

Catalytic hydrothermal liquefaction of alkali lignin for monophenols production over homologous biochar-supported copper catalysts in water.

Constructing an advanced catalytic system for the purposeful liquefaction of lignin into chemicals has presented a significant prospect for sustainable development. In this work, the catalytic process of mesoporous homologous biochar (HBC) derived from alkali lignin supported copper catalysts (Cu/HBC) was reported for catalytic liquefaction of alkali lignin to monophenols. The characterization results revealed HBC promoted the formation of metal-support strong interaction and the generation of oxygen vacancies, enhancing the acid sites of Cu/HBC. Under the optimal conditions (0.2 g alkali lignin, 280 °C, 0.05 g Cu/HBC, 6 h, 18 mL water), the monophenol yield reached 75.01 ± 0.76 mg/g, and the bio-oil yield was 57.98 ± 1.76%. The copious mesopores, high surface area, and rich acidic sites were responsible for the high activity of Cu/HBC, which significantly outperformed the controlled catalysts, such as HBC, commercial activated carbon (AC), and reported Ni/AC, Ni/MCM-41, etc. In four consecutive runs, the catalytic performance of Cu/HBC was only reduced by 3.65% per cycle. Interestingly, catechol was selectively produced with Cu/HBC, which provided an effective strategy for the conversion of G/S-type lignin to catechyl phenolics (C-type). These findings indicate that the Cu/HBC will be a promising substitution of noble metal-supported catalysts for conversion biomass into high value-added phenolics.

Lignin microparticles-reinforced cellulose filter paper for simultaneous removal of emulsified oils and dyes.

The presence of multiple pollutants in wastewater, often with complex interactions, poses a significant challenge for conventional membranes to effectively remove multiple pollutants simultaneously. Herein, a lignin microparticles-reinforced cellulose filter paper (FP@AL-LS-DA) was fabricated via an aldol condensation between lignin and cellulose filter paper and cross-linking with dopamine hydrochloride (DA), which showed desired rejection of oil-in-water emulsions and dyes. Characterizations revealed that the addition of lignin and DA effectively narrowed the pore size (from 4.45 µm to 2.01 µm) and enhanced the rigidity and stability of the cellulose filter paper, thus making it not easily damaged in the water environment and showing excellent tolerance to strong acid and high-salt environments. The oil-in-water emulsions removal efficiency was higher than 99 % even after ten times usage, and the oil flux was kept stable at 52.54 L·m-2·h-1, indicating that FP@AL-LS-DA had outstanding reusability and stability. Remarkably, FP@AL-LS-DA showed excellent removal efficiency (>99 %) for complex pollutants containing dyes and oil-in-water emulsions. In this work, we demonstrate a lignin microparticles-reinforced cellulose filter paper that is simple to prepare and can efficiently separate oil-in-water emulsions and remove dyes.

Synchronous catalytic depolymerization of alkaline lignin to monophenols with in situ-converted hierarchical zeolite for bio-polyurethane production.

Catalytic depolymerization of lignin to high-value chemicals is crucial to the comprehensive achievement of sustainable and economic concerns. Herein, we propose a green, practical, and economic strategy for the synchronous catalytic depolymerization of lignin based on in situ conversion of geopolymer precursor to hierarchical zeolite, using water as a mild solvent and without external H2, additives, co-catalysts or co-solvents. The in situ-converted hierarchical analcime (ANA) zeolite outperformed previously reported representative catalysts, such as PTA/MCM-41 and CuAlMgOx in lignin depolymerization with a high monophenol yield (95.61 ± 7.89 mg/g). The synergetic effect of the micro-mesoporous structure and enhanced acidic sites of the ANA played a vital role in regulating the monomer composition and the yield of monophenols. The obtained monophenols are rich in -OH groups and can be utilized as a substitute for petroleum resources, such as ethylene glycol or glycerin for the synthesis of bio-polyurethane foams (bio-PUFs). This work expands the scope of using biomass in a sustainable manner to make high-value chemicals and biomaterials.

A Low-Cost Biomimetic Heterostructured Multilayer Membrane with Geopolymer Microparticles for Broad-Spectrum Water Purification.

Membranes have received wide interest in water purification. However, the development of a low-cost and eco-friendly membrane with the desired structure for broad-spectrum water purification still remains a great challenge. Inspired by the hierarchical structure and functions of wood, a heterostructured multilayer membrane fabricated through a facile and "green" layer-by-layer self-assembly method was reported in this study. Specifically, the hydrophilic geopolymer microparticles were doped into sodium alginate matrix to construct "xylem" layers with numerous microchannels, and chitosan was used to build "phloem" layers with dense structures. The resultant biomimetic multilayer membrane displayed a distinct heterostructure and provided the desired rejection to different kinds of pollutants including nanoparticles, soluble dyes, and heavy metal ions, as well as emulsified oil droplets. Furthermore, the biomimetic membrane exhibited a superior stability in a long-term operation and an excellent recyclability for multiple usages for oil droplets removal. The proposed biomimetic membrane prepared in a completely "green" way possesses great potential in practical application for water purification and separation.