A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma.

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation.

Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: a narrative review.

Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes.

Leveraging a global, federated, real-world data network to optimize investigator-initiated pediatric clinical trials: the TriNetX Pediatric Collaboratory Network.

Objective: Clinical research networks facilitate collaborative research, but data sharing remains a common barrier.

Materials And Methods: The TriNetX platform provides real-time access to electronic health record (EHR)-derived, anonymized data from 173 healthcare organizations (HCOs) and tools for queries and analysis. In 2022, 4 pediatric HCOs worked with TriNetX leadership to found the Pediatric Collaboratory Network (PCN), facilitated via a multi-institutional data-use agreement (DUA).

Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid malignancy with low 5-year survival and limited treatment options. We conducted an unbiased screening using FDA-approved drug and demonstrated that cetylpyridinium chloride (CPC), a component commonly found in mouthwash and known for its robust bactericidal and antifungal attributes, exhibits anticancer activity against human PDAC cells. CPC inhibited PDAC cell growth and proliferation by inducing paraptosis, rather than apoptosis.

Usage of Tranexamic Acid for Total Hip Arthroplasty: A Matched Cohort Analysis of 144,344 Patients.

The literature is inconclusive regarding the potential complications of tranexamic acid (TXA), an antifibrinolytic drug, for total hip arthroplasty (THA). The purpose of this study is to compare complication rates and patient outcomes between THA patients administered TXA vs. THA patients not administered TXA.

Antithrombotic Strategies for Patients With Peripheral Artery Disease: JACC Scientific Statement.

Patients with peripheral artery disease (PAD) experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease.

ITCH inhibits alkaliptosis in human pancreatic cancer cells through YAP1-dependent SLC16A1 activation.

Alkaliptosis is a type of pH-dependent cell death and plays an emerging role in tumor suppression. However, the key modulation mechanism of alkaliptosis remains largely unknown. In particular, the nucleus, as the centre of genetic and metabolic regulation, is crucial for the regulation of cellular life.

Targeted DNA-seq and RNA-seq of Reference Samples with Short-read and Long-read Sequencing.

Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions.

The TBI Model Systems Neighborhood Socioeconomic Disadvantage Index (TBIMS-NSDI): Development and Comparison to Individual Socioeconomic Characteristics.

Objective: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI).

Setting: Community.

Participants: People enrolled in the TBI Model Systems National Database (TBIMS NDB).

PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network.

Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs.

Oxidative cell death in cancer: mechanisms and therapeutic opportunities.

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress.

mTORC2-driven chromatin cGAS mediates chemoresistance through epigenetic reprogramming in colorectal cancer.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor that initiates a STING-dependent innate immune response, binds tightly to chromatin, where its catalytic activity is inhibited; however, mechanisms underlying cGAS recruitment to chromatin and functions of chromatin-bound cGAS (ccGAS) remain unclear. Here we show that mTORC2-mediated phosphorylation of human cGAS serine 37 promotes its chromatin localization in colorectal cancer cells, regulating cell growth and drug resistance independently of STING. We discovered that ccGAS recruits the SWI/SNF complex at specific chromatin regions, modifying expression of genes linked to glutaminolysis and DNA replication.

Reverse versus anatomic total shoulder arthroplasty: A large matched cohort analysis.

Introduction: The annual utilization of reverse total shoulder arthroplasty (RTSA) and anatomic total shoulder arthroplasty (ATSA) has grown exponentially, in part due to the expanded indications of RTSA. This evolution in shoulder arthroplasty prompts the need to evaluate outcomes between ATSA and RTSA. However, many other studies comparing outcomes between ATSA and RTSA lacked a large nationally-represented sample, a matched cohort analysis, or both.

Maternal linoleic acid-rich diet ameliorates bilirubin neurotoxicity in offspring mice.

Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring.

The effect of remimazolam-based total intravenous anesthesia versus sevoflurane-based inhalation anesthesia on emergence delirium in children undergoing tonsillectomy and adenoidectomy: study protocol for a prospective randomized controlled trial.

Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy. This is a monocentric, prospective, randomized, double-blind clinical trial.

MA-mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8 T cells and phagocytosis of macrophages.

Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC).

Ciprofloxacin is a novel anti-ferroptotic antibiotic.

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear.

Identification of Hypoxia-ALCAM Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance.

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM macrophages, and exhausted CD8 T cells around the tumor boundary.