A trispecific antibody induces potent tumor-directed T-cell activation and antitumor activity by CD3/CD28 co-engagement.

Aim: A novel CD19xCD3xCD28 trispecific antibody with a tandem single-chain variable fragments (scFv) structure was developed for the treatment of B-cell malignancies. Methods: The trispecific antibody in inducing tumor-directed T-cell activation and cytotoxicity was evaluated in vitro and in vivo and compared with its bispecific counterpart BiTE-CD19xCD3 lacking a CD28-targeting domain. Results: The trispecific antibody with a co-stimulatory domain exhibited augmented T-cell activation and memory T-cell differentiation capability and it induced faster tumor cell lysis than the bispecific antibody. RNAseq analysis revealed that the trispecific antibody modulates CD3/TCR complex-derived signal and upregulates antiapoptotic factors to influence the survival of T cells. Conclusion: By CD3/CD28 co-engagement, the trispecific antibody demonstrated its advantages in T-cell immunity and potential use as a more powerful and long-lasting T-cell engager.

T-cell based immunotherapies are a type of treatment that stimulates the body's own immune system to fight cancer. They have grown in popularity in recent years and have had impressive results in cancer treatment. One type of T-cell immunotherapy is a T-cell engager antibody. This is a type of molecule that redirects the body's immune cells to recognise and kill cancer cells. In this study, we developed a new type of T-cell engager antibody to treat two types of blood and bone marrow cancer. The antibody works by joining immune cells and cancer cells close together, to help activate the immune cells for cancer killing. This new type of T-cell engager antibody worked better than previous versions. It helped the immune cells survive longer and kill cancer more effectively. This means the new antibody might be better at treating people who have these types of cancers, but more testing in humans needs to be done.

Enhanced methane production from the co-digestion of food waste and thermally hydrolyzed sludge filtrate.

Although many technologies can be applied to sewage sludge (SS) and food waste (FW) treatment, high investment and operational costs, high land occupation, and the "not-in-my-backyard" effect pose many challenges in practice. Thus, it is important to develop and utilize low-carbon or negative-carbon technologies to tackle the carbon problem. This paper proposes a method of anaerobic co-digestion of FW and SS, thermally hydrolyzed sludge (THS), or THS filtrate (THF) to enhance their methane potential. Compared to the co-digestion of SS with FW, the methane yield of the co-digestion of THS and FW was 9.7-69.7% higher, and that of the co-digestion of THF and FW was 11.1-101.1% higher. The synergistic effect was weakened with the addition of THS but enhanced with the addition of THF, potentially owing to the change in humic substances. Filtration removed most humic acids (HAs) from THS but retained fulvic acids (FAs) in THF. Moreover, THF produced 71.4% of the methane yield of THS, although only 25% of the organic matter permeated from THS to THF. This indicated that hardly biodegradable substances remained in the dewatering cake and were removed from anaerobic digestion systems. The results indicate that the co-digestion of THF and FW is an effective way to enhance methane production.

Embedding ruthenium nanoparticles in the shell layer of titanium zirconium oxide hollow spheres to catalyze the degradation of alkali lignin under mild condition.

To catalyze the degradation of lignin in refractory wastewater efficiently, a new nanocomposite with Ru nanoparticles embedded on the surface of TiZrO4 hollow spheres was fabricated with three method a "sol-gel + calcination + vacuum-impregnation" template method, and the unique binary composition of TiZrO4/Ru prevented the aggregation of Ru and keep its high activity. During 3-h catalytic-oxidation at 160 °C and 2.0 MPa O2, 98% alkali lignin was degraded and 70% organic carbon was mineralized with the catalysis of TiZrO4/Ru, while the values were only 50% and 25% without analysts. The catalyst increased the catalytic-oxidation rate constant k1 (h-1) of alkali lignin from 0.282 h-1 to 1.175 h-1 because of high-efficiency hydroxyl radical production, as determined by EPR. LC-OCD showed that the catalyst decomposed alkali lignin with molecular weight 1-2 kDa to small molecules. Butyl acetate was the main intermediate product, which should be derived from the auto synthesis of butanol and acetic acid. In addition to high conversion efficiency, the catalyst had good stability with 95% capability after five cycles. In real biogas slurry treatment, an increase of biochemical to COD ratio from 0.28 to 0.51, with obvious decoloration, indicated TiZrO4/Ru enhanced the biodegradability of the refractory wastewater significantly.

Measurement of electron transfer through cytochrome P450 protein on nanopillars and the effect of bound substrates.

Electron transfer in cytochrome P450 enzymes is a fundamental process for activity. It is difficult to measure electron transfer in these enzymes because under the conditions typically used they exist in a variety of states. Using nanotechnology-based techniques, gold conducting nanopillars were constructed in an indexed array. The P450 enzyme CYP2C9 was attached to each of these nanopillars, and conductivity measurements made using conducting probe atomic force microscopy under constant force conditions. The conductivity measurements were made on CYP2C9 alone and with bound substrates, a bound substrate-effector pair, and a bound inhibitor. Fitting of the data with the Poole-Frenkel model indicates a correlation between the barrier height for electron transfer and the ease of CYP2C9-mediated metabolism of the bound substrates, though the spin state of iron is not well correlated. The approach described here should have broad application to the measurement of electron transfer in P450 enzymes and other metalloenzymes.

An investigation into the feasibility of myoglobin-based single-electron transistors.

Myoglobin single-electron transistors were investigated using nanometer-gap platinum electrodes fabricated by electromigration at cryogenic temperatures. Apomyoglobin (myoglobin without the heme group) was used as a reference. The results suggest single-electron transport is mediated by resonant tunneling with the electronic and vibrational levels of the heme group in a single protein. They also represent a proof-of-principle that proteins with redox centers across nanometer-gap electrodes can be utilized to fabricate single-electron transistors. The protein orientation and conformation may significantly affect the conductance of these devices. Future improvements in device reproducibility and yield will require control of these factors.

Characterization and dye decolorization ability of an alkaline resistant and organic solvents tolerant laccase from Bacillus licheniformis LS04.

A new bacterial strain exhibiting laccase activity was isolated from forest soil and was identified as Bacillus licheniformis LS04. The spore laccase of B. licheniformis LS04 demonstrated a broad pH range for catalyzing substrates. It was quite stable at high temperature and alkaline pH. There was no loss of laccase activity after 10 days incubation at pH 9.0, and about 16% of the initial activity was detected after 10h at 80°C. In addition, the spore laccase was tolerant towards 1M of NaCl and 30% of organic solvents. Reactive black 5, reactive blue 19 and indigo carmine were decolorized by the spore laccase in the absence of mediator. Meanwhile, the decolorization process was efficiently promoted when acetosyringone was present, with more than 80% of color removal in 1h at pH 6.6 or 9.0. The unusual properties indicated a high potential in industrial applications for this novel spore laccase.

All-semiconductor active plasmonic system in mid-infrared wavelengths.

Metal-based plasmonics has a wide range of important applications but is subject to several drawbacks. In this paper, we propose and investigate an all-semiconductor-based approach to plasmonics in mid-infrared (MIR) wavelength range using InAs heterostructures. Our results show that InAs heterostructures are ideal for plasmonics with the shortest plasmon wavelength among common semiconductors. More importantly, as we will show, InAs heterostructures are superior to metal-based plasmonics for MIR applications due to much reduced loss, improved confinement, and ease of tunability of resonant wavelengths through carrier density. Finally, we propose and investigate a monolithic all-semiconductor integrated active plasmonic system with active source, waveguide, and detector all integrated on a chip, realizable in a single epitaxial growth process. Such an all semiconductor based system can be advantageous not only in plasmonics, but also in active metamaterials.