NKp46 enhances type 1 innate lymphoid cell proliferation and function and anti-acute myeloid leukemia activity.

NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that NKp46 is indispensable for expressing IL-2 receptor-α (IL-2Rα) by non-NK liver-resident type-1 innate lymphoid cells (ILC1s). Deletion of NKp46 reduces IL-2Rα on ILC1s by downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity in vitro and in vivo.

Regulation of PD-L1 glycosylation and advances in cancer immunotherapy.

Protein glycosylation plays a versatile role in regulating homeostasis, such as cell migration, protein sorting, and the immune response. Drugs aimed at targeting glycosylation have strong implications for immunity enhancement, diagnosis, and cancer regression. Programmed death-ligand 1 (PD-L1), expressed in cancer or antigen-presenting cells, binds to programmed cell death protein 1 (PD-1) and suppresses T cells.

High-resolution spatially resolved proteomics of complex tissues based on microfluidics and transfer learning.

Despite recent advances in imaging- and antibody-based methods, achieving in-depth, high-resolution protein mapping across entire tissues remains a significant challenge in spatial proteomics. Here, we present parallel-flow projection and transfer learning across omics data (PLATO), an integrated framework combining microfluidics with deep learning to enable high-resolution mapping of thousands of proteins in whole tissue sections. We validated the PLATO framework by profiling the spatial proteome of the mouse cerebellum, identifying 2,564 protein groups in a single run.

Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO): A protocol for an international prospective multicentre service evaluation across the United Kingdom and Ireland.

Introduction: Given its proximity to the central nervous system, surgical site infections (SSIs) after craniotomy (SSI-CRAN) represent a serious adverse event. SSI-CRAN are associated with substantial patient morbidity and mortality. Despite the recognition of SSI in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to skin closure, specifically in patients with brain tumors.

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

A Regulatory Circuits Analysis Tool, "miRCuit," Helps Reveal Breast Cancer Pathways: Toward Systems Medicine in Oncology.

A systems medicine understanding of the regulatory molecular circuits that underpin breast cancer is essential for early cancer detection and precision/personalized medicine in clinical oncology. Transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) control gene expression and cell biology, and by extension, serve as pillars of the regulatory circuits that determine human health and disease. We report here the development of a regulatory circuit analysis program, , constructing 10 different types of regulatory elements involving messenger RNA, miRNA, lncRNA, and TFs.

Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.

In spite of significant advancements in diagnosis and treatment, cancer remains one of the major threats to human health due to its ability to cause disease with high morbidity and mortality. A multifactorial and multitargeted approach is required towards intervention of the multitude of signaling pathways associated with carcinogenesis inclusive of angiogenesis and metastasis. In this context, plants provide an immense source of phytotherapeutics that show great promise as anticancer drugs.

MTIOT: Identifying HPV subtypes from multiple infection data.

Persistent infection with high-risk human papillomavirus (hrHPV) is a major cause of cervical cancer. The effectiveness of current HPV-DNA testing, which is crucial for early detection, is limited in several aspects, including low sensitivity, accuracy issues, and the inability to perform comprehensive hrHPV typing. To address these limitations, we introduce MTIOT (Multiple subTypes In One Time), a novel detection method that utilizes machine learning with a new multichannel integration scheme to enhance HPV-DNA analysis.

Mechanically Triggered Protein Desulfurization.

The technology of native chemical ligation and postligation desulfurization has greatly expanded the scope of modern chemical protein synthesis. Here, we report that ultrasonic energy can trigger robust and clean protein desulfurization, and we developed an ultrasound-induced desulfurization (USID) strategy that is simple to use and generally applicable to peptides and proteins. The USID strategy involves a simple ultrasonic cleaning bath and an easy-to-use and easy-to-remove sonosensitizer, titanium dioxide.

WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome.

Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months.

Identification of a novel cuproptosis inducer that induces ER stress and oxidative stress to trigger immunogenic cell death in tumors.

Cuproptosis, a copper-dependent form of regulated cell death, has been implicated in the progression and treatment of various tumors. The copper ionophores, such as Disulfiram (DSF), an FDA-approved drug previously used to treat alcohol dependence, have been found to induce cuproptosis. However, the limited solubility and effectiveness of the combination of DSF and copper ion restrict its widespread application.

EXO: A Dual-Mechanism Stimulator of Interferon Genes Activator for Cancer Immunotherapy.

As natural agonists of the stimulator of interferon genes (STING) protein, cyclic dinucleotides (CDNs) can activate the STING pathway, leading to the expression of type I interferons and various cytokines. Efficient activation of the STING pathway in antigen-presenting cells (APCs) and tumor cells is crucial for antitumor immune response. Tumor-derived exosomes can be effectively internalized by APCs and tumor cells and have excellent potential to deliver CDNs to the cytoplasm of APCs and tumor cells.

Altered retinal vasculature in childhood cancer survivors: Data from the German CVSS-study.

Aims: Childhood cancer is a risk factor for cardiovascular diseases in later life. Retinal examination allows to non-invasively observe the vasculature of an end-organ. We observe alterations in long-term childhood cancer survivors (CCS).

A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei.

Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P.

Human Plasma-Derived Exosomes: A Promising Carrier System for the Delivery of Hydroxyurea to Combat Breast Cancer.

The aim of the present study was to investigate the potential of human plasma derived exosomes for the delivery of hydroxyurea to enhance its therapeutic efficacy in breast cancer. Plasma derived exosomes were isolated using differential centrifugation along with ultrafiltration method. Hydroxyurea was encapsulated in exosomes using a freeze-thaw method.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

dsDAP: An efficient method for high-abundance DNA-encoded library construction in mammalian cells.

DNA-encoded libraries are invaluable tools for high-throughput screening and functional genomics studies. However, constructing high-abundance libraries in mammalian cells remains challenging. Here, we present dsDNA-assembly-PCR (dsDAP), a novel Gibson-assembly-PCR strategy for creating DNA-encoded libraries, offering improved flexibility and efficiency over previous methods.

Targeted internalization and activation of glycosidic switch liposomes by a biological macromolecule mPEG×EphA2 increases therapeutic efficacy against lung cancer.

Glycosidic switch liposome (GSL) technology efficiently encapsulates and stabilizes potent anticancer drugs in liposomes using a reversible glucuronide ester. Enzymatic hydrolysis of the glucuronide switch in target cell lysosomes produces parental drug. Our study examined the potential of a bispecific macromolecule, a polyethylene glycol (PEG) engager (mPEG×EphA2), generated by fusing a humanized anti-methoxy PEG (mPEG) Fab with an anti-EphA2 single-chain antibody, to increase GSL uptake into cancer cells and boost the anticancer activity by targeting PEG on GSL and an internalizing tumor antigen.

Optogenetics in medicine: innovations and therapeutic applications.

Optogenetics, an innovative approach integrating photonics and genetic engineering, enables precise control over molecular and cellular processes, opening up exciting new opportunities for precision-guided medicine. In this review, we highlight recent advances in optogenetic tools and their applications across a range of medical conditions, including vision restoration in retinitis pigmentosa via light-activated ion channels, precise immune response modulation in cancer immunotherapy, and blood glucose management in diabetes through controllable drug release. Optogenetics also plays a critical role in bioelectronic medicine, enabling seamless communication between electronic systems and biological tissues to enhance therapeutic precision.

Recent Advancements and Future Perspectives on Molecular Biomarkers in Adult Lower-Grade Gliomas.

There has been a significant paradigm shift in the clinical management of lower-grade glioma patients given the recent updates to the 2021 World Health Organization classification along with long-term results from randomized phase III clinical trials. As a result, we are now better able to diagnose and assign patients to the most appropriate treatment course. This review provides a comprehensive summary of the most robust and reliable molecular biomarkers for adult lower-grade gliomas and discusses current challenges facing this patient population that future correlative biology studies combined with advancements in technologies could help overcome.

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

Navigating Tumor Microenvironment Barriers with Nanotherapeutic Strategies for Targeting Metastasis.

Therapeutic strategy for efficiently targeting cancer cells needs an in-depth understanding of the cellular and molecular interplay in the tumor microenvironment (TME). TME comprises heterogeneous cells clustered together to translate tumor initiation, migration, and proliferation. The TME mainly comprises proliferating tumor cells, stromal cells, blood vessels, lymphatic vessels, cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), and cancer stem cells (CSC).