A tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses.

It is a challenge to invigorate tumor-infiltrating lymphocytes without causing immune-related adverse events, which also stands as a primary factor contributing to resistance against cancer immunotherapies. Interleukin (IL)-15 can potently promote expansion and activation of T cells, but its clinical use has been limited by dose-limiting toxicities. In this study, we develop a tumor-conditional IL-15 (pro-IL-15), which masks IL-15 with steric hindrance caused by Fc fragment and IL-15Rα-sushi domain.

Ultrastable halide perovskite CsPbBr photoanodes achieved with electrocatalytic glassy-carbon and boron-doped diamond sheets.

Halide perovskites exhibit exceptional optoelectronic properties for photoelectrochemical production of solar fuels and chemicals but their instability in aqueous electrolytes hampers their application. Here we present ultrastable perovskite CsPbBr-based photoanodes achieved with both multifunctional glassy carbon and boron-doped diamond sheets coated with Ni nanopyramids and NiFeOOH. These perovskite photoanodes achieve record operational stability in aqueous electrolytes, preserving 95% of their initial photocurrent density for 168 h of continuous operation with the glassy carbon sheets and 97% for 210 h with the boron-doped diamond sheets, due to the excellent mechanical and chemical stability of glassy carbon, boron-doped diamond, and nickel metal.

Swept coded aperture real-time femtophotography.

Single-shot real-time femtophotography is indispensable for imaging ultrafast dynamics during their times of occurrence. Despite their advantages over conventional multi-shot approaches, existing techniques confront restricted imaging speed or degraded data quality by the deployed optoelectronic devices and face challenges in the application scope and acquisition accuracy. They are also hindered by the limitations in the acquirable information imposed by the sensing models.

Coseismic Deformation Field and Fault Slip Distribution Inversion of the 2020 Jiashi 6.4 Earthquake: Considering the Atmospheric Effect with Sentinel-1 Data Interferometry.

Due to some limitations associated with the atmospheric residual phase in Sentinel-1 data interferometry during the Jiashi earthquake, the detailed spatial distribution of the line-of-sight (LOS) surface deformation field is still not fully understood. This study, therefore, proposes an inversion method of coseismic deformation field and fault slip distribution, taking atmospheric effect into account to address this issue. First, an improved inverse distance weighted (IDW) interpolation tropospheric decomposition model is utilised to accurately estimate the turbulence component in tropospheric delay.

Revealing the stochastic kinetics evolution of photocatalytic CO reduction.

Investigating kinetic mechanisms to design efficient photocatalysts is critical for improving photocatalytic CO reduction, but the stochastic photo-physical/chemical properties of kinetics remain unclear. Herein, we propose a statistical study to discuss the stochastic feature evolution of photocatalytic systems. The uncertainties of light absorption, charge carrier migration, and surface reaction are described by nonparametric estimation methods in the proposed model, which includes the effect of operational and material parameters.

Single-shot compressed optical field topography.

Femtosecond lasers are powerful in studying matter's ultrafast dynamics within femtosecond to attosecond time scales. Drawing a three-dimensional (3D) topological map of the optical field of a femtosecond laser pulse including its spatiotemporal amplitude and phase distributions, allows one to predict and understand the underlying physics of light interaction with matter, whose spatially resolved transient dielectric function experiences ultrafast evolution. However, such a task is technically challenging for two reasons: first, one has to capture in single-shot and squeeze the 3D information of an optical field profile into a two-dimensional (2D) detector; second, typical detectors are only sensitive to intensity or amplitude information rather than phase.

Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains.

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human V domain, F6, which we generated by sequentially panning large phage-displayed V libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region.

Synergistic surface oxygen defect and bulk Ti defect engineering on SrTiO for enhancing photocatalytic overall water splitting.

SrTiO as a photocatalytic overall water splitting material has received extensive attention in recent years, while effectively suppressing Ti is the key to enhancing the photocatalytic performance. Herein, a polymerizable complexation method is employed to enable Al uniformly enter into SrTiO lattice for reducing Ti, and substituting Ti with the formation of oxygen vacancy. Thus, the photogenerated carrier transport is promoted, and the resulting appropriate surface oxygen vacancy is also conducive to the adsorption of water molecules and OH*.

What Role Does the Incident Light Intensity Play in Photocatalytic Conversion of CO : Attenuation or Intensification?

Artificial photoreduction of CO is vital for the sustainable development of human beings via solar energy storage in stable chemicals. This process involves intricate light-matter interactions, but the role of incident light intensity in photocatalysis remains obscure. Herein, the influence of excitation intensity on charge kinetics and photocatalytic activity is investigated.

Efficient solar-driven CO-to-fuel conversion via Ni/MgAlO @SiO nanocomposites at low temperature.

Solar-driven CO-to-fuel conversion assisted by another major greenhouse gas CH is promising to concurrently tackle energy shortage and global warming problems. However, current techniques still suffer from drawbacks of low efficiency, poor stability, and low selectivity. Here, a novel nanocomposite composed of interconnected Ni/MgAlO nanoflakes grown on SiO particles with excellent spatial confinement of active sites is proposed for direct solar-driven CO-to-fuel conversion.

Effective killing of cells expressing CD276 (B7-H3) by a bispecific T cell engager based on a new fully human antibody.

The pancaner molecule CD276 (B7-H3) is an attractive target for antibody based therapy. We identified from a large (10) phage-displayed single-chain variable fragment (scFv) library, a fully human antibody, B11, which bound with high avidity (K=0.4 nM) to CD276.

Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.

Cluster of differentiation-22 (CD22) belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies.

Highly Selective Production of Ethanol Over Hierarchical Bi@Bi MoO Composite via Bicarbonate-Assisted Photocatalytic CO Reduction.

Photocatalytic CO reduction is a sustainable and inexpensive method to solve the energy crisis and the greenhouse effect. However, the major stumbling blocks such as poor product selectivity, low yield of the multi-carbon products, and serious recombination of electron-hole pairs hinder practical application of photocatalysts. Herein, a high-performance Bi@Bi MoO photocatalyst, Bi nanoparticles grown on the surface of Bi MoO nanosheets with oxygen vacancies, was fabricated via a simple solvothermal approach.

The reduced form of the antibody CH2 domain.

Among the immunoglobulin domains, the CH2 domain has the lowest thermal stability, which also depends on amino acid sequence and buffer conditions. To further identify factors that influence CH2 folding and stability, we characterized the domain in the reduced form using differential scanning fluorimetry and nuclear magnetic resonance. We show that the CH2 domain can fold, similarly to the disulfide-bridged form, without forming a disulfide-bridge, even though the protein contains two Cys residues.

Protocol for constructing large size human antibody heavy chain variable domain (V) library and selection of SARS-CoV-2 neutralizing antibody domains.

This protocol is a comprehensive guide to phage display-based selection of virus neutralizing V antibody domains. It details three optimized parts including (1) construction of a large-sized (theoretically > 10) naïve human antibody heavy chain domain library, (2) SARS-CoV-2 antigen expression and stable cell line construction, and (3) library panning for selection of SARS-CoV-2-specific antibody domains. Using this protocol, we identified a high-affinity neutralizing human V antibody domain, V ab8, which exhibits high prophylactic and therapeutic efficacy.

Compressed ultrafast tomographic imaging by passive spatiotemporal projections.

Existing streak-camera-based two-dimensional (2D) ultrafast imaging techniques are limited by long acquisition time, the trade-off between spatial and temporal resolutions, and a reduced field of view. They also require additional components, customization, or active illumination. Here we develop compressed ultrafast tomographic imaging (CUTI), which passively records 2D transient events with a standard streak camera.

Developability Assessment of an Isolated C2 Immunoglobulin Domain.

The IgG C2 domain continues to hold promise for the development of new therapeutic entities because of its bifunctional role as a biomarker and effector protein. The need for further understanding of molecular stability and aggregation in therapeutic proteins has led to the development of a breakthrough quantum cascade laser microscope to allow for real-time comparability assessment of an array of related proteins in solution upon thermal perturbation. Our objective was to perform a comprehensive developability assessment of three similar monoclonal antibody (mAb) fragments: C2, C2s, and m01s.

Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection.

Effective therapies are urgently needed for the SARS-CoV-2/COVID-19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from large phage-displayed Fab, scFv, and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD.

Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice.

The development of an effective vaccine against SARS-CoV-2 is urgently needed. We generated SARS-CoV-2 RBD-Fc fusion protein and evaluated its potency to elicit neutralizing antibody response in mice. RBD-Fc elicited a higher neutralizing antibodies titer than RBD as evaluated by a pseudovirus neutralization assay and a live virus based microneutralization assay.

High Potency of a Bivalent Human V Domain in SARS-CoV-2 Animal Models.

Novel COVID-19 therapeutics are urgently needed. We generated a phage-displayed human antibody V domain library from which we identified a high-affinity V binder ab8. Bivalent V, V-Fc ab8, bound with high avidity to membrane-associated S glycoprotein and to mutants found in patients.

Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold.

Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used for the construction of a large library, lCAT6, of engineered human VHs. This library was panned against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein.