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Coherent phonons in the Terahertz (THz) regime have gained attention as potential candidates for next-generation high-speed, low-energy information carriers in atomically thin phononic or phonon-integrated on-chip devices. Nevertheless, achieving efficient control of the phonon generation dynamics over THz coherent phonons continues to pose a considerable challenge. In this work, we explore THz coherent phonon generation in exfoliated van der Waals (vdW) flakes of WSe2 on Au (WSe2/Au) and Si (WSe2/Si) by using time-resolved pump–probe spectroscopy. The generation of THz coherent phonons was studied as a function of the WSe2 layer thickness and laser wavelength. Notably, a significant enhancement in THz coherent phonon generation was observed in the WSe2/Au structure, but only within a specific range of WSe2 thicknesses and laser wavelengths. The results from numerical simulations, which consider a self-hybridized optical cavity depending on WSe2 thickness and optical reflectance and Raman spectroscopy measurements, all align well with the time-domain observations of THz coherent phonon generation. We propose that the observed enhancement in THz coherent phonon generation is strongly influenced by light–matter interactions in the WSe2 cavity, a mechanism that may be applicable to a broader range of vdW materials. These findings offer promising insights for the development of THz phononic or phonon-integrated devices. 

Abstract While significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they’re computationally demanding due to rare transitions between biologically relevant equilibrium states. In this study, we present DynamicBind, a deep learning method that employs equivariant geometric diffusion networks to construct a smooth energy landscape, promoting efficient transitions between different equilibrium states. DynamicBind accurately recovers ligand-specific conformations from unbound protein structures without the need for holo-structures or extensive sampling. Remarkably, it demonstrates state-of-the-art performance in docking and virtual screening benchmarks. Our experiments reveal that DynamicBind can accommodate a wide range of large protein conformational changes and identify cryptic pockets in unseen protein targets. As a result, DynamicBind shows potential in accelerating the development of small molecules for previously undruggable targets and expanding the horizons of computational drug discovery. 

Electrical Impedance Spectroscopy (EIS) is a non-invasive and label-free technology that can characterize and discriminate cells based on their dielectric properties at a wide range of frequency. This characterization method has not been utilized for small extracellular vesicles (exosomes) with heterogenous and nano-scale size distribution. Here, we developed a novel label-free microelectronic impedance spectroscopy for non-invasive and rapid characterization of exosomes based on their unique dielectric properties. The device is comprised of an insulator-based dielectrophoretic (iDEP) module for exosomes isolation followed by an impedance spectroscopy utilizing the embedded micro-electrodes. This device is capable of distinguishing between exosomes harvested from different cellular origins as the result of their unique membrane and cytosolic compositions at a wide range of frequency. Therefore, it has the potential to be further evolved as a rapid tool for characterization of pathogenic exosomes in clinical settings. 

Electrical Impedance Spectroscopy (EIS) has been widely used as a label-free and rapid characterization method for the analysis of cells in clinical research. However, the related work on exosomes (40–150 nm) and the particles of similar size has not yet been reported. In this study, we developed a new Lab-on-a-Chip (LOC) device to rapidly entrap a cluster of sub-micron particles, including polystyrene beads, liposomes, and small extracellular vesicles (exosomes), utilizing an insulator-based dielectrophoresis (iDEP) scheme followed by measuring their impedance utilizing an integrated electrical impedance sensor. This technique provides a label-free, fast, and non-invasive tool for the detection of bionanoparticles based on their unique dielectric properties. In the future, this device could potentially be applied to the characterization of pathogenic exosomes and viruses of similar size, and thus, be evolved as a powerful tool for early disease diagnosis and prognosis. 

Abstract Early detection of cancer can significantly reduce mortality and save lives. However, the current cancer diagnosis is highly dependent on costly, complex, and invasive procedures. Thus, a great deal of effort has been devoted to exploring new technologies based on liquid biopsy. Since liquid biopsy relies on detection of circulating biomarkers from biofluids, it is critical to isolate highly purified cancer‐related biomarkers, including circulating tumor cells (CTCs), cell‐free nucleic acids (cell‐free DNA and cell‐free RNA), small extracellular vesicles (exosomes), and proteins. The current clinical purification techniques are facing a number of drawbacks including low purity, long processing time, high cost, and difficulties in standardization. Here, we review a promising solution, on‐chip electrokinetic‐based methods, that have the advantage of small sample volume requirement, minimal damage to the biomarkers, rapid, and label‐free criteria. We have also discussed the existing challenges of current on‐chip electrokinetic technologies and suggested potential solutions that may be worthy of future studies. 

Background Despite approval of immunotherapy for a wide range of cancers, the majority of patients fail to respond to immunotherapy or relapse following initial response. These failures may be attributed to immunosuppressive mechanisms co-opted by tumor cells. However, it is challenging to use conventional methods to systematically evaluate the potential of tumor intrinsic factors to act as immune regulators in patients with cancer. Methods To identify immunosuppressive mechanisms in non-responders to cancer immunotherapy in an unbiased manner, we performed genome-wide CRISPR immune screens and integrated our results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two rate-limiting steps of cancer immunotherapy, namely, T cell tumor infiltration and T cell-mediated tumor killing. Results Our studies revealed two distinct types of immune resistance regulators and demonstrated their potential as therapeutic targets to improve the efficacy of immunotherapy. Among them, PRMT1 and RIPK1 were identified as a dual immune resistance regulator and a cytotoxicity resistance regulator, respectively. Although the magnitude varied between different types of immunotherapy, genetically targeting PRMT1 and RIPK1 sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment. Interestingly, a RIPK1-specific inhibitor enhanced the antitumor activity of T cell-based and anti-OX40 therapy, despite limited impact on T cell tumor infiltration. Conclusions Collectively, the data provide a rich resource of novel targets for rational immuno-oncology combinations.