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Sansevieria trifasciata fibre (STF) is a lignocellulosic material which could be utilised for reinforcement composites. Surface modification is often needed to improve the compatibility of hydrophilic STF and hydrophobic resin. In this study, treatments for natural fibres to attain superhydrophobic properties were carried out using silica nanoparticles and fluorosilane. Sansevieria trifasciata fibres (STF) were subjected to treatment by deposition of silica (SiO2) nanoparticles which were prepared by the sol-gel method, then followed by modification with fluorosilane, namely 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane (PFOTS). The presence of SiO2 nanoparticles and PFOTS were evaluated using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). The crystallisation properties and thermal behaviour of STF were studied through X-ray diffraction (XRD) and thermogravimetric (TGA) analysis, respectively. The hydrophobicity of STF was determined by water contact angle (WCA) measurement. The results show that nanoscale SiO2 particles were deposited on the STF surface, and PFOTS were covalently linked to them. The SiO2 nanoparticles provide surface roughness to the fibres, whereas the long-chain fluorine on PFOTS lowered the surface free energy, and their combination in these treatments has successfully modified the STF surface from hydrophilic into superhydrophobic with a WCA of 150° and sliding angle of less than 10°. Altogether, a non-toxic, simple, and promising method of imparting hydrophobicity on natural fibres was developed, opening new opportunities for these fibres as reinforcement for composite parts.

Epoxy nano composites containing micro and nano silica were prepared by varying the filler’s weight loading as an attempt to investigate the effects of incorporating these fillers in influencing its mechanical properties. Mechanical properties characterizations include the evaluation of tensile. The mechanical properties of the epoxy composites were found to tremendously increase as both micro and nano silica were added together at a 1:1 wt.% ratio. For example, the highest values of Young’s modulus were recorded to be 5.39 GPa for 25 wt.% loading (12.5 wt.% Micro + 12.5 wt.% nano), while Young’s modulus values of 5.22 MPa and 5.32 MPa were recorded for micro and nano silica, respectively, at the same weight loading. The most outstanding results were observed at 25 wt.% hybrids (12.5 wt.% micro silica + 12.5 wt.% nano silica), where the values of Young’s modulus were increased by 228% compared to the neat epoxy. This study successfully demonstrated synergistic effects demonstrated by combining micro and nano silica fillers, which created an interaction that significantly enhanced the Young’s modulus of epoxy composites.

Granulation is an important step during the production of urea granules. Most of the commercial binders used for granulation are toxic and non-biodegradable. In this study, a fully biodegradable and cost-effective starch-based binder is used for urea granulation in a fluidized bed granulator. The effect of binder properties such as viscosity, surface tension, contact angle, penetration time, and liquid bridge bonding force on granulation performance is studied. In addition, the effect of fluidized bed process parameters such as fluidizing air inlet velocity, air temperature, weight of primary urea particles, binder spray rate, and binder concentration is also evaluated using response surface methodology. Based on the results, binder with higher concentration demonstrates higher viscosity and higher penetration time that potentially enhance the granulation performance. The viscous Stokes number for binder with higher concentration is lower than critical Stokes number that increases coalescence rate. Higher viscosity and lower restitution coefficient of urea particles result in elastic losses and subsequent successful coalescence. Statistical analysis indicate that air velocity, air temperature, and weight of primary urea particles have major effects on granulation performance. Higher air velocity increases probability of collision, whereby lower temperature prevents binder to be dried up prior to collision. Findings of this study can be useful for process scale-up and industrial application.

The objective of the research was to understand and improve the unusual physical and atomization properties of the complexes/adhesives derived from the tapioca starch by addition of borate and urea. The characterization of physical properties of the synthesized adhesives was carried out by determining the effect of temperature, shear rate, and mass concentration of thickener/stabilizer on the complex viscosity, density, and surface tension. In later stage, phenomenological analyses of spray jet breakup of heated complexes were performed in still air. Using a high speed digital camera, the jet breakup dynamics were visualized as a function of the system input parameters. The further analysis of the grabbed images confirmed the strong influence of the input processing parameters on full cone spray patternation. It was also predicted that the heated starch adhesive solutions generate a dispersed spray pattern by utilizing the partial evaporation of the spraying medium. Below 40°C of heating temperature, the radial spray cone width and angle did not vary significantly with increasing Reynolds and Weber numbers at early injection phases leading to increased macroscopic spray propagation. The discharge coefficient, mean flow rate, and mean flow velocity were significantly influenced by the load pressure but less affected by the temperature.

Multiobjective (MO) optimization is an emerging field which is increasingly being encountered in many fields globally. Various metaheuristic techniques such as differential evolution (DE), genetic algorithm (GA), gravitational search algorithm (GSA), and particle swarm optimization (PSO) have been used in conjunction with scalarization techniques such as weighted sum approach and the normal-boundary intersection (NBI) method to solve MO problems. Nevertheless, many challenges still arise especially when dealing with problems with multiple objectives (especially in cases more than two). In addition, problems with extensive computational overhead emerge when dealing with hybrid algorithms. This paper discusses these issues by proposing an alternative framework that utilizes algorithmic concepts related to the problem structure for generating efficient and effective algorithms. This paper proposes a framework to generate new high-performance algorithms with minimal computational overhead for MO optimization.

The hot water sprays are an important part of many industrial processes, where the detailed knowledge of physical phenomena involved in jet transportation, interaction, secondary breakup, evaporation, and coalescence of droplets is important to reach more efficient processes. The objective of the work was to study the water spray jet breakup dynamics, vortex cloud formation, and droplet size distribution under varying temperature and load pressure. Using a high speed camera, the spray patterns generated by axisymmetric full cone nozzles were visualized as a function water temperature and load pressure. The image analysis confirmed that the spray cone angle and width do not vary significantly with increasing Reynolds and Weber numbers at early injection phases leading to increased macroscopic spray propagation. The formation and decay of semitorus like vortex clouds were also noticed in spray structures generated at near water boiling point temperature. For the nozzle with smallest orifice diameter (1.19 mm), these vortex clouds were very clear at 90°C heating temperature and 1 bar water load pressure. In addition, the sauter mean diameter (SMD) of the spray droplets was also measured by using Phase Doppler Anemometry (PDA) at different locations downstream of the nozzle exit. It was noticed that SMD varies slightly w.r.t. position when measured at room temperature whereas at higher temperature values, it became almost constant at distance of 55 mm downstream of the nozzle exit.

Vapor-deposited inverted perovskite solar cells utilizing self-assembled monolayer (SAM) as hole transport material have gained significant attention for their high efficiencies and compatibility with silicon/perovskite monolithic tandem devices. However, as a small molecule, the SAM layer suffers low thermal tolerance in comparison with other metal oxide or polymers, rendering poor efficiency in solar device with high-temperature (> 160 °C) fabricating procedures. In this study, a dual modification approach involving AlO x and F-doped phenyltrimethylammonium bromide (F-PTABr) layers is introduced to enhance the buried interface. The AlO x dielectric layer improves the interface contact and prevents the upward diffusion of SAM molecules during the vapor-solid reaction at 170 °C, while the F-PTABr layer regulates crystal growth and reduces the interfacial defects. As a result, the AlO x /F-PTABr-treated perovskite film exhibits a homogeneous, pinhole-free morphology with improved crystal quality compared to the control films. This leads to a champion power conversion efficiency of 21.53% for the inverted perovskite solar cells. Moreover, the encapsulated devices maintained 90% of the initial efficiency after 600 h of ageing at 85 °C in air, demonstrating promising potential for silicon/perovskite tandem application., (© 2024 Wiley‐VCH GmbH.)

Quasi-3D plasmonic nanostructures are in high demand for their ability to manipulate and enhance light-matter interactions at subwavelength scales, making them promising building blocks for diverse nanophotonic devices. Despite their potential, the integration of these nanostructures with optical sensors and imaging systems on a large scale poses challenges. Here, a robust technique for the rapid, scalable, and seamless replication of quasi-3D plasmonic nanostructures is presented straight from their production wafers using a microbubble process. This approach not only simplifies the integration of quasi-3D plasmonic nanostructures into a wide range of standard and custom optical imaging devices and sensors but also significantly enhances their imaging and sensing performance beyond the limits of conventional methods. This study encompasses experimental, computational, and theoretical investigations, and it fully elucidates the operational mechanism. Additionally, it explores a versatile set of options for outfitting nanophotonic devices with custom-designed plasmonic nanostructures, thereby fulfilling specific operational criteria., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear. Therefore, identification of effective therapeutic strategies is urgently needed to overcome therapy resistance. Transcriptome-based analysis, in vitro studies and functional assays identified that cisplatin-resistant ovarian cancer cells express high levels of OSMR compared to cisplatin sensitive cells. Furthermore, OSMR expression associated with a module of integrin family genes and predominantly linked with integrin αV (ITGAV) and integrin β3 (ITGB3) for cisplatin resistance. Using ectopic expression and knockdown approaches, we proved that OSMR directly regulates ITGAV and ITGB3 gene expression through STAT3 activation. Notably, targeting OSMR using anti-OSMR human antibody inhibited the growth and metastasis of ovarian cancer cells and sensitized cisplatin treatment. Taken together, our results underscore the pivotal role of OSMR as a requirement for cisplatin resistance in ovarian cancer. Notably, OSMR fostered the expression of a distinct set of integrin genes, which in turn resulted into a crosstalk between OSMR and integrins for signaling activation that is critical for cisplatin resistance. Therefore, targeting OSMR emerges as a promising and viable strategy to reverse cisplatin-resistance in ovarian cancer., (© 2024. The Author(s).)

Ion migration is one of the most critical challenges that affects the stability of metal-halide perovskite solar cells (PSCs). However, the current arsenal of available strategies for solving this issue is limited. Here, novel perovskite active layers following the concept of ordered structures with functional units (OSFU) to intrinsically suppress ion migration, in which a three-dimensional (3D) perovskite layer is deposited by vapor deposition for light absorption and a 2D layer is deposited by solution process for ion inhibition, are constructed. As a promising result, the activation energy of ion migration increases from 0.36 eV for the conventional perovskite to 0.54 eV for the OSFU perovskite. These devices exhibit substantially enhanced operational stability in comparison with the conventional ones, retaining >85% of their initial efficiencies after 1200 h under ISOS-L-1. Moreover, the OSFU devices show negligible fatigue behavior with a robust performance under light/dark cycling aging test (ISOS-LC-1 protocol), which demonstrates the promising application of functional motif theory in this field., (© 2024 Wiley‐VCH GmbH.)

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive "transient" and "durable" expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination., (© 2024. The Author(s).)

Lithium bis(trifluoromethane) sulfonamide (LiTFSI) and oxygen-doped organic semiconductors have been frequently used to achieve record power conversion efficiencies of perovskite solar cells (PSCs). However, this conventional doping process is time-consuming and leads to poor device stability due to the incorporation of Li ions. Herein, aiming to accelerate the doping process and remove the Li ions, we report an alternative p-doping process by mixing a new small-molecule organic semiconductor, N 2 , N 2 , N 7 , N 7 -tetrakis (4-methoxyphenyl)-9-(4-(octyloxy) phenyl)-9 H carbazole-2,7-diamine (labeled OH44) and its preoxidized form OH44 + (TFSI - ). With this method, a champion efficiency of 21.8% has been achieved for small-area PSCs, which is superior to the state-of-the-art EH44 and comparable with LiTFSI and oxygen-doped spiro -OMeTAD. Moreover, the stability of OH44-based PSCs is improved compared with those of EH44, maintaining more than 85% of its initial efficiency after aging in an ambient condition without encapsulation for 1000 h. In addition, we achieved efficiencies of 14.7 and 12.6% for the solar modules measured with a metal mask of 12.0 and 48.0 cm 2 , respectively, which demonstrated the scalability of this method.

Linear gratings polarizers provide remarkable potential to customize the polarization properties and tailor device functionality via dimensional tuning of configurations. Here, we extensively investigate the polarization properties of single- and double-layer linear grating, mainly focusing on self-aligned bilayer linear grating (SABLG), serving as a wire grid polarizer in the mid-wavelength infrared (MWIR) region. Computational analyses revealed the polarization properties of SABLG, highlighting enhancement in TM transmission and reduction in TE transmission compared to single-layer linear gratings (SLG) due to optical cavity effects. As a result, the extinction ratio is enhanced by approximately 2724-fold in wavelength 3-6 μm. Furthermore, integrating the specially designed SABLG with an MWIR InAs/GaSb Type-II Superlattice (T2SL) photodetector yields a significantly enhanced spectral responsivity. The TM-spectral responsivity of SABLG is enhanced by around twofold than the bare device. The simulation methodology and analytical analysis presented herein provide a versatile route for designing optimized polarimetric structures integrated into infrared imaging devices, offering superior capabilities to resolve linear polarization signatures., (© 2024. The Author(s).)

Hardware security is not a new problem but is ever-growing in consumer and medical domains owing to hyperconnectivity. A physical unclonable function (PUF) offers a promising hardware security solution for cryptographic key generation, identification, and authentication. However, electrical PUFs using nanomaterials or two-dimensional (2D) transition metal dichalcogenides (TMDCs) often have limited entropy and parameter space sources, both of which increase the vulnerability to attacks and act as bottlenecks for practical applications. We report an electrical PUF with enhanced entropy as well as parameter space by incorporating 2D TMDC heteronanostructures into field-effect transistors (FETs). Lateral heteronanostructures of 2D molybdenum disulfide and tungsten disulfide serve as a potent entropy source. The variable feature of FETs is further leveraged to enhance the parameter space that provides multiple challenge-response pairs, which are essential for PUFs. This combination results in stably repeatable yet highly variable FET characteristics as alternative electrical PUFs. Comprehensive PUF performance analyses validate the bit uniformity, reproducibility, uniqueness, randomness, false rates, and encoding capacity. The 2D material heteronanostructure-driven electrical PUFs with strong FET-to-FET variability can potentially be augmented as an immediately deployable and scalable security solution for various hardware devices.

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

Vapor deposition is a promising technology for the mass production of perovskite solar cells. However, the efficiencies of solar cells and modules based on vapor-deposited perovskites are significantly lower than those fabricated using the solution method. Emerging evidence suggests that large defects are generated during vapor deposition owing to a specific top-down crystallization mechanism. Herein, a hybrid vapor deposition method combined with solvent-assisted recrystallization for fabricating high-quality large-area perovskite films with low defect densities is presented. It is demonstrated that an intermediate phase can be formed at the grain boundaries, which induces the secondary growth of small grains into large ones. Consequently, perovskite films with substantially reduced grain boundaries and defect densities are fabricated. Results of temperature-dependent charge-carrier dynamics show that the proposed method successfully suppresses all recombination reactions. Champion efficiencies of 21.9% for small-area (0.16 cm 2 ) cells and 19.9% for large-area (10.0 cm 2 ) solar modules under AM 1.5 G irradiation are achieved. Moreover, the modules exhibit high operational stability, i.e., they retain >92% of their initial efficiencies after 200 h of continuous operation., (© 2023 Wiley-VCH GmbH.)

The deep space's coldness (∼4 K) provides a ubiquitous and inexhaustible thermodynamic resource to suppress the cooling energy consumption. However, it is nontrivial to achieve subambient radiative cooling during daytime under strong direct sunlight, which requires rational and delicate photonic design for simultaneous high solar reflectivity (>94%) and thermal emissivity. A great challenge arises when trying to meet such strict photonic microstructure requirements while maintaining manufacturing scalability. Herein, we demonstrate a rapid, low-cost, template-free roll-to-roll method to fabricate spike microstructured photonic nanocomposite coatings with Al 2 O 3 and TiO 2 nanoparticles embedded that possess 96.0% of solar reflectivity and 97.0% of thermal emissivity. When facing direct sunlight in the spring of Chicago (average 699 W/m 2 solar intensity), the coatings show a radiative cooling power of 39.1 W/m 2 . Combined with the coatings' superhydrophobic and contamination resistance merits, the potential 14.4% cooling energy-saving capability is numerically demonstrated across the United States.

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility., (© 2023. The Author(s).)

We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC 50 values of 3.4, 2.2 and 7.4 ng ml -1 for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10-100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Inverse-vulcanized polymeric sulfur has received considerable attention for application in waste-based infrared (IR) polarizers with high polarization sensitivities, owing to its high transmittance in the IR region and thermal processability. However, there have been few reports on highly sensitive polymeric sulfur-based polarizers by replication of pre-simulated dimensions to achieve a high transmission of the transverse magnetic field (T TM ) and extinction ratio (ER). Herein, a 400-nanometer-pitch mid-wavelength infrared bilayer linear polarizer with self-aligned metal gratings is introduced on polymeric sulfur gratings integrated with a spacer layer (SM-polarizer). The dimensions of the SM-polarizer can be closely replicated using pre-simulated dimensions via a systematic investigation of thermal nanoimprinting conditions. Spacer thickness is tailored from 40 to 5100 nm by adjusting the concentration of polymeric sulfur solution during spin-coating. A tailored spacer thickness can maximize T TM in the broadband MWIR region by satisfying Fabry-Pérot resonance. The SM-polarizer yields T TM of 0.65, 0.59, and 0.43 and ER of 3.12 × 10 3 , 5.19 × 10 3 , and 5.81 × 10 3 at 4 µm for spacer thicknesses of 90, 338, and 572 nm, respectively. This demonstration of a highly sensitive and cost-effective SM-polarizer opens up exciting avenues for infrared polarimetric imaging and for applications in polarization manipulation., (© 2022 Wiley-VCH GmbH.)

Chiral morphology has been intensively studied in various fields including biology, organic chemistry, pharmaceuticals, and optics. On-demand and dynamic chiral inversion not only cannot be realized in most intrinsically chiral materials but also has mostly been limited to chemical or light-induced methods. Herein, we report reversible real-time magneto-mechanical chiral inversion of a three-dimensional (3D) micropillar array between achiral, clockwise, and counterclockwise chiral arrangements. Inspired by the flower corolla, achiral arrays of five and six radially arranged semicylindrical micropillars were employed as model systems to investigate the dynamic symmetry properties of arrays consisting of odd and even numbers of micropillars, respectively. Each micropillar underwent twisting actuation with a different twisting angle depending on the angle with the magnetic field direction and magnetic flux density, thereby collectively changing the chirality from the achiral to chiral state. Importantly, the morphological handedness of the micropillars was inverted within a few seconds by manipulating the direction of the magnetic field. A chiral morphology consisting of magnetically twisted micropillars was shape-fixed by the introduction of a polymeric binder. This binder could be simply washed off to return the shape-fixed twisted micropillars to their initial straight state. Magnetically programmable and reproducible 3D flower corolla-like micropillar arrays are expected to expand the potential of shape-reconfigurable devices that require real-time chiral manipulation in ambient environments.

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv) 2 design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models for individual cocktail antibodies, and computational simulations suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and multiple variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth., (© 2022. The Author(s).)

The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro . The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy., Competing Interests: JJX, XG, XCL, NZ, ZA, CCZ, and XCL were inventors of a patent application covering anti-LAIR1 antibodies and their uses. NZ, ZA, and CCZ hold equity in and have Sponsored Research Agreements with Immune-Onc Therapeutics, Inc. XCL and TH are employees and hold equities of Immune-Onc Therapeutics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Gui, Deng, Chen, Chen, Liu, Ku, Tan, Huang, He, Zhang, Lewis, Chen, Xu, Xu, Huang, Liao, Zhang, An and Zhang.)

Background: Microglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs., Methods: To specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)-derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory cytokines. Effects of the LILRB2 antagonist antibody on microglial responses to amyloid plaques were further studied in vivo using stereotaxic grafted microglia in 5XFAD mice., Results: We confirmed the expression of both LILRB2 and TREM2 in human brain microglia using immunofluorescence. Upon co-ligation of the LILRB2 and TREM2 by shared ligands oAβ or PS, TREM2 signaling was significantly inhibited. We identified a monoclonal antibody (Ab29) that blocks LILRB2/ligand interactions and prevents TREM2 signaling inhibition mediated by LILRB2. Further, Ab29 enhanced microglia phagocytosis, TREM2 signaling, migration, and cytokine responses to the oAβ-lipoprotein complex in hMGL and microglia cell line HMC3. In vivo studies showed significantly enhanced clustering of microglia around plaques with a prominent increase in microglial amyloid plaque phagocytosis when 5XFAD mice were treated with Ab29., Conclusions: This study revealed for the first time the molecular mechanisms of LILRB2-mediated inhibition of TREM2 signaling in microglia and demonstrated a novel approach of enhancing TREM2-mediated microglia functions by blocking LILRB2-ligand interactions. Translationally, a LILRB2 antagonist antibody completely rescued the inhibition of TREM2 signaling by LILRB2, suggesting a novel therapeutic strategy for improving microglial functions., (© 2022. The Author(s).)