Polymer-based chemo-immunotherapy: Combining immunogenic cell death induction and PD-L1 blockade enhances antitumor immunity in melanoma.

Melanoma remains a challenging malignancy despite the significant outcomes achieved with immune checkpoint inhibitor (ICI) monotherapy. Here, we investigated a polymer-based chemo-immunotherapy strategy combining KT-1, a backbone-degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin conjugate that induces immunogenic cell death (ICD), with MPPA, a multivalent HPMA copolymer-peptide antagonist of PD-L1 (PPA: (NYSKPTDRQYHF). In B16F10 melanoma, a 3-day dosing schedule significantly outperformed 7-day dosing.

Characterization of Heparin Interactions With Recombinant Rodent Stabilin-2/Hyaluronic Acid Receptor for Endocytosis (HARE).

Stabilin-2 is the primary scavenger for hyaluronan (HA) and binds to over two dozen other ligands including chondroitin sulfates, heparin, oxidized/acetylated LDL, etc. Although rat liver sinusoidal endothelial cells are the preferred primary cell lines and animal for physiological studies of Stab2/HARE, the rat recombinant protein has never been characterized. Since the rat Stab2/HARE has a high degree homology to mouse Stab2/HARE which has been cloned, our hypothesis is that the rat receptor is identical to mouse and very similar to the human receptor.

Mesuaferroic acid H suppresses HepG2 cell proliferation by disrupting iron homeostasis via transferrin targeting.

Mesua ferrea L., a medicinal plant widely utilized in traditional Chinese and South Asia medicine, demonstrates diverse pharmacological activities, with particularly notable anti-cancer properties. However, the specific bioactive constituents responsible for these effects and their underlying mechanisms remain unclear.

Neurotransmitters: an emerging target for therapeutic resistance to tumor immune checkpoint inhibitors.

The critical role of neurotransmitters in the resistance to tumor immune checkpoint inhibitor (ICI) is becoming increasingly significant in therapeutic contexts. ICIs work by enhancing antitumor immunity through the blockade of the PD-1/PD-L1 and CTLA-4 pathways. However, only 20% of patients experience durable efficacy, and the challenge of drug resistance limits the clinical application of these therapies.

Self-Assembling Multi-Antigen T Cell Hybridizers for Precision Immunotherapy of Multiple Myeloma.

Bispecific T-cell engagers show promise in treating multiple myeloma (MM), but challenges remain in adaptability and targeting flexibility. This paper presents a novel T-cell based immunotherapy, Multi-Antigen TCell Hybridizers (MATCH), a modular, self-assembling T-cell engager designed for versatile and patient-specific cancer targeting. MATCH consists of two components: a B-cell-targeting Fab' fragment conjugated to a 25-base morpholino oligonucleotide (Fab'-MORF1) and a T-cell engaging anti-CD3 Fab' fragment conjugated to the complementary morpholino oligonucleotide (Fab'-MORF2).

Enhancing ferroelectric stability: wide-range of adaptive control in epitaxial HfO/ZrO superlattices.

The metastability of the polar phase in HfO, despite its excellent compatibility with the complementary metal-oxide-semiconductor process, remains a key obstacle for its industrial applications. Traditional stabilization approaches, such as doping, often induce crystal defects and impose constraints on the thickness of ferroelectric HfO thin films. These limitations render the ferroelectric properties vulnerable to degradation, particularly due to phase transitions under operational conditions.

Arylsulfatase B induces melanoma apoptosis by the ubiquitin ligase COP1.

Previous experiments in the syngeneic, murine, and subcutaneous model of malignant melanoma and human melanoma cells showed that treatment by recombinant human (rh) Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) markedly reduced the volume of tumors, improved survival, and inhibited invasiveness. In this report, the impact of ARSB on the progression of metastatic, pulmonary B16F10 melanomas in C57BL/6J mice is addressed, and the underlying apoptotic mechanism by which ARSB inhibits melanoma growth is identified. Exogenous ARSB, which has mannose 6-phosphate attachments, acts through insulin-like growth factor 2 receptor (IGF2R), a cation-independent mannose-6-phosphate receptor, and increases expression of constitutive photomorphogenic protein (COP)1.

CD38-targeted antibody-polymer drug conjugates for enhanced treatment of multiple myeloma.

Multiple myeloma (MM) remains a formidable disease, especially in relapsed or refractory cases when there are limited treatment options. In this study, we introduce two polymer-antibody drug conjugates (pADCs), ISA-P-EPI (U6244-021) and DARA-P-EPI (U6244-031), which contain semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugate attached to CD38-targeting antibodies Isatuximab (ISA) and Daratumumab (DARA). These pADCs enhance therapeutic efficacy by combining the specificity of ISA and DARA with the cytotoxic potency of EPI while preserving antibody function.

TEAD switches interacting partners along neural progenitor lineage progression to execute distinct functions.

The TEAD family of transcription factors is best known as the DNA-binding factor in the Hippo pathway, where these factors act by interacting with transcriptional coactivators YAP and TAZ (YAP/TAZ). Despite the importance of the Hippo pathway, the in vivo functions of TEAD in mammals have not been well established. By comparing mouse mutants lacking TEAD1 and TEAD2 (TEAD1/2) with those lacking YAP/TAZ, we found that TEAD1/2 have both YAP/TAZ-dependent and YAP/TAZ-independent functions during ventral telencephalon development.

STCC enhances spatial domain detection through consensus clustering of spatial transcriptomics data.

The rapid advance of spatially resolved transcriptomics technologies has yielded substantial spatial transcriptomics data. Deriving biological insights from these data poses nontrivial computational and analysis challenges, of which the most fundamental step is spatial domain detection (or spatial clustering). Although a number of tools for spatial domain detection have been proposed in recent years, their performance varies across data sets and experimental platforms.

scMINER: a mutual information-based framework for clustering and hidden driver inference from single-cell transcriptomics data.

Single-cell transcriptomics data present challenges due to their inherent stochasticity and sparsity, complicating both cell clustering and cell type-specific network inference. To address these challenges, we introduce scMINER (single-cell Mutual Information-based Network Engineering Ranger), an integrative framework for unsupervised cell clustering, transcription factor and signaling protein network inference, and identification of hidden drivers from single-cell transcriptomic data. scMINER demonstrates superior accuracy in cell clustering, outperforming five state-of-the-art algorithms and excelling in distinguishing closely related cell populations.

Two-component T-cell immunotherapy enables antigen pre-targeting to reduce cytokine release without forfeiting efficacy.

Contemporary T-cell immunotherapies, despite impressive targeting precision, are hindered by aberrant cytokine release and restrictive targeting stoichiometry. We introduce a two-component T-cell immunotherapy targeting B-cell malignancies: Multi-Antigen T-Cell Hybridizers (MATCH). This split antibody technology differs from current therapies by separating cancer cell-targeting components from T cell-engaging components.

RNA secondary structure prediction by conducting multi-class classifications.

Generating valid predictions of RNA secondary structures is challenging. Several deep learning methods have been developed for predicting RNA secondary structures. However, they commonly adopt post-processing steps to adjust the model output to produce valid predictions, which are complicated and could limit the performance.

PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer.

Following successful design of polymer enhanced rituximab-epirubicin (EPI) conjugates targeted to non-Hodgkin lymphoma (Zhang et al. 2017), we developed U6244-051 that consists of anti-PD-L1 antibody (αPD-L1) and semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugates (ST-P-EPI); the latter is attached to αPD-L1 via Cu-free azide/alkyne cycloaddition. This new polymer-enhanced antibody-drug conjugate (pADC) not only exhibits a high drug-to-antibody ratio (DAR ∼ 30-40) but also integrates immune checkpoint blockade with long-lasting immunogenic anticancer chemotherapy, providing an innovative chemo-immuno combination modality.

Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: Artificial intelligence analysis.

Primary Central Nervous System Lymphoma is an aggressive central nervous system neoplasm with poor response to pharmacological treatment, partially due to insufficient drug delivery across blood-brain barrier. In this study, we developed a novel therapy for this lymphoma by combining a targeted nanopolymer treatment with an immune checkpoint inhibitor antibody (anti-PD-1). A N-(2-hydroxypropyl)methacrylamide copolymer-based nanoconjugate was designed to block tumor cell c-Myc oncogene expression by antisense oligonucleotide.

Spotiphy enables single-cell spatial whole transcriptomics across an entire section.

Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations.

Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution.

The variation of transcriptome size across cell types significantly impacts single-cell RNA sequencing (scRNA-seq) data normalization and bulk RNA-seq cellular deconvolution, yet this intrinsic feature is often overlooked. Here we introduce ReDeconv, a computational algorithm that incorporates transcriptome size into scRNA-seq normalization and bulk deconvolution. ReDeconv introduces a scRNA-seq normalization approach, Count based on Linearized Transcriptome Size (CLTS), which corrects differential expressed genes typically misidentified by standard count per 10 K normalization, as confirmed by orthogonal validations.

TEAD switches interacting partners along neural progenitor lineage progression to execute distinct functions.

The TEAD family of transcription factors are best known as the DNA-binding factor in the Hippo pathway, where they act by interacting with transcriptional coactivators YAP and TAZ (YAP/TAZ). Despite the importance of the Hippo pathway, the in vivo functions of TEAD in mammals have not been well established. By comparing mouse mutants lacking TEAD1 and TEAD2 (TEAD1/2) to those lacking YAP/TAZ, we found that TEAD1/2 have both YAP/TAZ-dependent and -independent functions during ventral telencephalon development.

Characterization of heparin interactions with Clostridioides difficile toxins and its potential as anti-CDI therapeutics.

Clostridioides difficile (C. difficile) infection (CDI) is a life-threatening healthcare-associated infection occurring worldwide. C.

Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.

Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection.

Polycaprolactone/polylactic acid nanofibers incorporated with butyl hydroxyanisole /HP-β-CD assemblies for improving fruit storage quality.

In this study, the inclusion complex was prepared with butyl hydroxyanisole (BHA) as the functional substance and 2-hydroxypropyl beta-cyclodextrin (HP-β-CD) as the main molecule by ultrasound mediation. The inclusion complex was mixed with polycaprolactone (PCL)/polylactic acid (PLA), and nanofiber films loaded with different concentrations of BHA/HP-β-CD inclusion complex were prepared by electrospinning for fruit preservation. The scanning electron microscopy and infrared spectroscopy characterization results showed that HP-β-CD successfully embedded BHA in the cavity.

Production, Characterization, and Application of Hydrophobin-Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near-Infrared Imaging.

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability.

Highly Responsive Polar Vortices in All-Ferroelectric Heterostructures.

The discovery of polar vortices and skyrmions in ferroelectric-dielectric superlattices [such as (PbTiO)/(SrTiO)] has ushered in an era of novel dipolar topologies and corresponding emergent phenomena. The key to creating such emergent features has generally been considered to be related to counterpoising strongly polar and non-polar materials thus creating the appropriate boundary conditions. This limits the utility these materials can have, however, by rendering (effectively) half of the structure unresponsive to applied stimuli.

GraphPCA: a fast and interpretable dimension reduction algorithm for spatial transcriptomics data.

The rapid advancement of spatial transcriptomics technologies has revolutionized our understanding of cell heterogeneity and intricate spatial structures within tissues and organs. However, the high dimensionality and noise in spatial transcriptomic data present significant challenges for downstream data analyses. Here, we develop GraphPCA, an interpretable and quasi-linear dimension reduction algorithm that leverages the strengths of graphical regularization and principal component analysis.

Clinical research progress of targeted therapy combined with immunotherapy for advanced cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a common and highly malignant form of cancer that has shown high rates of morbidity and mortality in recent years. The prognosis for cholangiocarcinoma is generally poor due to its aggressive nature and high recurrence rate. Most patients are diagnosed in the middle or late stages of the disease, making surgical treatment challenging.