Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.

Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.

M13, an anthraquinone compound isolated from Morinda officinalis alleviates the progression of the osteoarthritis via the regulation of STAT3.

Background: Osteoarthritis (OA) is characterized by the progressive deterioration of articular cartilage, leading to joint pain and functional impairment. OA severely impacts quality of life and presents a substantial societal burden. Currently, effective treatment options remain limited.

Nodal Yield From Neck Dissection Predicts the Anti-Tumor Immune Response in Head and Neck Cancers.

Background: Lymph node count (LNC) from neck dissection has been associated with undernutrition and survival in head and neck squamous cell carcinoma (HNSCC). As local components of the immune system, cervical lymph nodes may reflect anti-tumor immune status. This study investigates the relationship between decreased LNC, formation of tertiary lymphoid structures (TLS), and primary tumor infiltration by lymphocytes in undernourished patients.

Physiologically based pharmacokinetic modeling and simulation of topiramate in populations with renal and hepatic impairment and considerations for drug-drug interactions.

Topiramate (TPM) is a broad-spectrum antiepileptic drug (AED) commonly prescribed for approved and off-label uses. Routine monitoring is suggested for clinical usage of TPM in special population due to its broad side effect profile. Therefore, it is crucial to further explore its pharmacokinetic characteristics.

Cylindrical vector beam multiplexing holography employing spin-decoupled phase modulation metasurface.

Cylindrical vector beams (CVBs) hold considerable promise as high-capacity information carriers for multiplexing holography due to their mode orthogonality. In CVB holography, phase holograms are encoded onto the wave-front of CVBs with different mode orders while preserving their independence during reconstruction. However, a major challenge lies in the limited ability to manipulate the spatial phase and polarization distribution of CVBs independently.

Deep Integration of Fiber-Optic Communication and Sensing Systems Using Forward-Transmission Distributed Vibration Sensing and on-off Keying.

The deep integration of communication and sensing technology in fiber-optic systems has been highly sought after in recent years, with the aim of rapid and cost-effective large-scale upgrading of existing communication cables in order to monitor ocean activities. As a proof-of-concept demonstration, a high-degree of compatibility was shown between forward-transmission distributed fiber-optic vibration sensing and an on-off keying (OOK)-based communication system. This type of deep integration allows distributed sensing to utilize the optical fiber communication cable, wavelength channel, optical signal and demodulation receiver.

Distributed Vibration Sensing Based on a Forward Transmission Polarization-Generated Carrier.

For distributed fiber-optic sensors, slowly varying vibration signals down to 5 mHz are difficult to measure due to low signal-to-noise ratios. We propose and demonstrate a forward transmission-based distributed sensing system, combined with a polarization-generated carrier for detection bandwidth reduction, and cross-correlation for vibration positioning. By applying a higher-frequency carrier signal using a fast polarization controller, the initial phase of the known carrier frequency is monitored and analyzed to demodulate the vibration signal.

Cascaded partitioned phase modulation for cross-connection of orbital angular momentum mode and polarization multiplexing channels.

Multi-dimensional orbital angular momentum (OAM) mode multiplexing provides a promising route for enlarging communication capacity and establishing comprehensive networks. While multi-dimensional multiplexing has gained advancements, the cross-connection of these multiplexed channels, especially involving modes and polarizations, remains challenging due to the needs for multi-mode interconversion and on-demand polarization control. Herein, we propose an OAM mode-polarization cross-transformation solution via cascaded partitioned phase modulation, which enables the divergently separated OAM modes to be independently phase-imposed within distinct spatial regions, leading to the synergistic conversion operation of mode and polarization channels.

A general pHLA-CD80 scaffold fusion protein to promote efficient antigen-specific T cell-based immunotherapy.

Inadequate antigen-specific T cells activation hampers immunotherapy due to complex antigen presentation. In addition, therapeutic T cell expansion is constrained by slow expansion rates and limited functionality. Herein, we introduce a model fusion protein termed antigen-presenting cell-mimic fusion protein (APC-mimic), designed to greatly mimicking the natural antigen presentation pattern of antigen-presenting cells and directly expand T cells both and .

DeepHLApan: A Deep Learning Approach for the Prediction of Peptide-HLA Binding and Immunogenicity.

Neoantigens are crucial in distinguishing cancer cells from normal ones and play a significant role in cancer immunotherapy. The field of bioinformatics prediction for tumor neoantigens has rapidly developed, focusing on the prediction of peptide-HLA binding affinity. In this chapter, we introduce a user-friendly tool named DeepHLApan, which utilizes deep learning techniques to predict neoantigens by considering both peptide-HLA binding affinity and immunogenicity.

Cross-connection of multiplexed cylindrical vector beams using off-axis spin-decoupled metasurfaces.

Cylindrical vector beam (CVB) multiplexing communication demands effective mode cross-connection techniques to establish communication networks. While methods like polarized grating and coordinate transformation have been developed for (de)multiplexing CVB modes, challenges persist in the cross-connection of these multiplexed mode channels, including multi-mode conversion and inhomogeneous polarization control. Herein, we present an independent off-axis spin-orbit interaction strategy utilizing spin-decoupled metasurfaces.

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy.

Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells.

CovEpiAb: a comprehensive database and analysis resource for immune epitopes and antibodies of human coronaviruses.

Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes.

Multi-dimensional cylindrical vector beam (de)multiplexing through cascaded wavelength- and polarization-sensitive metasurfaces.

Cylindrical vector beams (CVBs) exhibit great potential for multiplexing communication, owing to their mode orthogonality and compatibility with conventional wavelength multiplexing techniques. However, the practical application of CVB multiplexing communication faces challenges due to the lack of effective spatial polarization manipulation technologies for (de)multiplexing multi-dimensional physical dimensions of CVBs. Herein, we introduce a wavelength- and polarization-sensitive cascaded phase modulation strategy that utilizes multiple coaxial metasurfaces for multi-dimensional modulation of CVBs.

Structure-Guided and Phage-Assisted Evolution of Therapeutic Antibodies to Reverse On-Target Point Mutation-Mediated Resistance.

Resistance to therapeutic antibodies caused by on-target point mutations is a major obstacle in anticancer therapy, creating an "unmet clinical need." To tackle this problem, researchers are developing new generations of antibody drugs that can overcome the resistance mechanisms of existing agents. We have previously reported a structure-guided and phage-assisted evolution (SGAPAE) approach to evolve cetuximab, a therapeutic antibody, to effectively reverse the resistance driven by EGFR or EGFR mutations, without changing the binding epitope or compromising the antibody efficacy.

High-order orbital angular momentum mode-based phase shift-keying communication using phase difference modulation.

Orbital angular momentum (OAM) mode offers a promising modulation dimension for high-order shift-keying (SK) communication due to its mode orthogonality. However, the expansion of modulation order through superposing OAM modes is constrained by the mode-field mismatch resulting from the rapidly increased divergence with mode orders. Herein, we address this problem by propose a phase-difference modulation strategy that breaks the limitation of modulation orders via introducing a phase-difference degree of freedom (DoF) beyond OAM modes.

Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice.

Full-duplex cylindrical vector beam multiplexing communication using spin-dependent phase modulation metasurfaces.

Cylindrical vector beam (CVB) has recently gained attention as a promising carrier for signal multiplexing owing to its mode orthogonality. However, the full-duplex multiplexing communication has not been previously explored for the lack of effective technologies to parallelly couple and separate CVB modes. Herein, we present a full-duplex solution for CVB multiplexing communication that utilizes spin-dependent phase modulation metasurfaces.

Highly efficient synergistic activity of an α-L-arabinofuranosidase for degradation of arabinoxylan in barley/wheat.

Here, an α-L-arabinofuranosidase (termed TtAbf62) from is described, which efficiently removes arabinofuranosyl side chains and facilitates arabinoxylan digestion. The specific activity of TtAbf62 (179.07 U/mg) toward wheat arabinoxylan was the highest among all characterized glycoside hydrolase family 62 enzymes.

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets.

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function.

DeepTAP: An RNN-based method of TAP-binding peptide prediction in the selection of tumor neoantigens.

The transport of peptides from the cytoplasm to the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP) is a critical step in the intracellular presentation of cytotoxic T lymphocyte (CTL) epitopes. The development and application of computational methods, especially deep learning methods and new neural network strategies that can automatically learn feature representations with limited knowledge, provide an opportunity to develop fast and efficient methods to identify TAP-binding peptides. Herein, this study presents a comprehensive analysis of TAP-binding peptide sequences to derive TAP-binding motifs and preferences for N-terminal and C-terminal amino acids.

Soluble interleukin-2 receptor combined with interleukin-8 is a powerful predictor of future adverse cardiovascular events in patients with acute myocardial infarction.

Background: Little is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury.

Methods: This was a prospective, single-center cohort study.