RNF126 suppresses amino acid-mediated mTORC1 signaling pathway by ubiquitinating ILF3 in HEK293T cells.

The mammalian Target of Rapamycin Complex 1 (mTORC1) serves as a metabolic hub that integrates external nutrients to promote cell growth and metabolism, with its activation closely associated with accelerated cancer progression. Interleukin enhancer-binding factor 3 (ILF3) has been identified as a negative regulator of mTORC1 by tethering GATOR1/2 to the lysosomal membrane during amino acid sensing. However, the regulatory mechanisms of the ILF3-mediated mTORC1 signaling pathway remain unclear.

Advances in oral treatment of inflammatory bowel disease using protein-based nanoparticle drug delivery systems.

Inflammatory bowel disease (IBD) comprises chronic autoimmune disorders with significant morbidity, highlighting the need for advanced, noninvasive, targeted therapies. Protein-based nanoparticle drug delivery systems (PNP-DDSs) have emerged as promising platforms to overcome limitations of conventional IBD therapies by improving drug stability and bioavailability while enabling colon-specific delivery. This review systematically classifies PNP-DDSs derived from natural proteins (albumin, gelatin, silk fibroin, and plant-derived proteins) and discusses their design principles along with strategies for intestinal targeting, including particle size and surface charge modulation, stimuli-responsive release (triggered by pH, reactive oxygen species, or enzymes), and active targeting.

Personalized 3D Vaccine Integrates Immunotherapy and Antiangiogenic Therapy to Prevent Oral Squamous Cell Carcinoma Recurrence.

The immune-suppressive microenvironment and extensive tumor angiogenesis are key contributors to the high recurrence and mortality rates of oral squamous cell carcinoma (OSCC). To address these challenges, a personalized 3D-printed anti-tumor vaccine (3D-Vax-L) is developed that integrates whole tumor antigens from postoperative tissue lysates with the angiogenesis inhibitor, lenvatinib. This vaccine not only possesses inherent adjuvant properties but also mimics the functions of lymph nodes through its porous structure, facilitating the recruitment and maturation of immune cells.

An IL-15-modified NKp30×HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing.

Natural killer (NK) cells represent a promising effector population for tumor immunotherapy. Conventional NK cell engagers (NKCEs), primarily targeting CD16a, show efficacy but face limitations due to receptor polymorphisms and off-target toxicity. Here, we report the development and characterization of a novel trispecific NK cell engager (TriKE) simultaneously targeting the activating receptor NKp30 and the tumor-associated antigen HER2, integrated with a modified interleukin-15 (IL-15 N72D) fused to the IL-15Rα sushi domain (IL-15RαSu) to enhance NK cell proliferation and persistence.

Associations between the gut microbiota, immune cells, and different subtypes of epilepsy: A Mendelian randomization study.

Objective: The gut microbiota (GM) plays a role in epilepsy development via the microbiota-gut-brain axis. However, its relationship with various epilepsy subtypes and its mediating role through immune cells remain unclear. Thus, identifying the GM linked to specific epilepsy subtypes and investigating immune mechanisms to predict epilepsy risk, tailor treatments, and monitor outcomes are crucial.

Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation.

Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers. In this study, we explored the potential of human single-domain antibodies (UdAbs) as topical therapeutics for the targeted modulation of interleukin-33 (IL-33) in two mucosal-associated inflammatory disorders. The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway, despite not potently blocking the IL-33 receptor interaction.

Oral Lipid Nanoparticles for Improving the Efficiency of Drug Delivery Systems in Ulcerative Colitis: Recent Advances and Future Prospects.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent, recurrent, and relapsing inflammation of the mucosal layer. Its pathogenesis is complex and not yet fully understood, with current treatments mainly focused on alleviating symptoms through pharmacological methods. Direct drug administration for UC often leads to poor intestinal bioavailability, suboptimal targeting, and an increased risk of resistance.

Uniportal video-assisted thoracoscopic surgery does not increase recurrence rates following pneumonectomy in non-small cell lung cancer: a retrospective study from the National Cancer Center of China.

Background: The safety, feasibility, and potential benefits of uniportal video-assisted thoracoscopic surgery (U-VATS) pneumonectomy remain to be investigated. This study aimed to evaluate the postoperative outcomes, survival prognosis, and recurrence patterns in patients undergoing U-VATS versus those undergoing open pneumonectomy. The feasibility of U-VATS pneumonectomy in patients receiving neoadjuvant systemic therapy was also assessed.

A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer.

Anti-PD-(L)1 treatment is standard for non-small cell lung cancer (NSCLC), but patients show variable responses to the same regimen. The tumor immune microenvironment (TIME) is associated with immunotherapy response, yet the heterogeneous underlying therapeutic outcomes remain underexplored. We applied single-cell RNA and TCR sequencing (scRNA/TCR-seq) to analyze surgical tumor samples from 234 NSCLC patients post-neoadjuvant chemo-immunotherapy.

The miR-34a-5p Promotes Hippocampal Neuronal Ferroptosis in Epilepsy by Regulating SIRT1.

Epilepsy, one of the most prevalent neurological disorders, affects approximately 50 million individuals worldwide. MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of target genes at the post-transcriptional level by interacting with specific sequences of the target genes in a complementary manner, thus affecting a variety of biological processes. miR-34a-5p has been shown to be involved in the regulation of cellular ferroptosis, and we aimed to explore its expression in epilepsy and its mechanism of action in epileptic ferroptosis.

Integrated molecular characterization reveals the pathogenesis and therapeutic strategies of pulmonary blastoma.

Background: Pulmonary blastoma (PB) is a rare subtype of lung cancer. Currently, the underlying pathogenesis mechanisms of PB have not been fully illustrated, and the therapeutic approach for this entity is limited.

Methods: Whole-exome sequencing (WES), RNA sequencing, and DNA methylation profiling are applied to seven PB patients.

Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment.

Mechanisms of the Compound of Magnoliae Flos and Xanthii Fructus Essential Oils for the Treatment of Allergic Rhinitis based on the Integration of Network Pharmacology, Molecular Docking, and Animal Experiment.

Aim And Objective: Magnoliae Flos (Chinese name: Xin-Yi) and Xanthii Fructus (Chinese name: Cang-Er-Zi) are Chinese herbal medicines and have been used to treat allergic rhinitis (AR). However, the therapeutic effect, active ingredients, and probable processes of a compound of Magnoliae Flos and Xanthii Fructus in the form of essential oils (CMFXFEO) in treating AR have not been reported. This study aims to determine the efficacy of the CMFXFEO on ovalbumin (OVA)-induced AR in a rat model and to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of CMFXFEO against AR.

Association between glyphosate exposure and cardiovascular health using "Life's Essential 8" metrics in US adults.

Background: Glyphosate, as one of the most widely used herbicides worldwide, has been reclassified as a potential carcinogen and linked to multiple health problems. Recent data from animal experiments have proved its potential cardiovascular toxicity. However, whether glyphosate exposure influences human cardiovascular health at the population levels remains unknown.

The role of epigenetic methylations in thyroid Cancer.

Thyroid cancer (TC) represents one of the most prevalent endocrine malignancies, with a rising incidence worldwide. Epigenetic alterations, which modify gene expression without altering the underlying DNA sequence, have garnered significant attention in recent years. Increasing evidence underscores the pivotal role of epigenetic modifications, including DNA methylation, RNA methylation, and histone methylation, in the pathogenesis of TC.

Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.

Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion.

Hypoxia-inducible factor-1α can reverse the Adriamycin resistance of breast cancer adjuvant chemotherapy by upregulating transferrin receptor and activating ferroptosis.

Breast cancer is a common malignant tumor in women. Ferroptosis, a programmed cell death pathway, is closely associated with breast cancer and its resistance. The transferrin receptor (TFRC) is a key factor in ferroptosis, playing a crucial role in intracellular iron accumulation and the occurrence of ferroptosis.

Activation of the helper NRC4 immune receptor forms a hexameric resistosome.

Innate immune responses to microbial pathogens are regulated by intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) in both the plant and animal kingdoms. Across plant innate immune systems, "helper" NLRs (hNLRs) work in coordination with "sensor" NLRs (sNLRs) to modulate disease resistance signaling pathways. Activation mechanisms of hNLRs based on structures are unknown.

MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1.

Background: TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1.

Effects of PGE1 on the ERS pathway in neonatal rats with hyperoxic lung injury.

Background: With the increase in the number of low birth weight infants, oxygen therapy is more widely used. However, chronic high-concentration oxygen environments lead to hyperoxic lung injury in children, which in turn leads to bronchopulmonary dysplasia (BPD). PGE1 is widely used in the clinic for its ability to inhibit inflammation and improve circulation.

IL-7R Expression Correlates with Prognosis in Breast Cancer.

Background: The tumor microenvironment (TME) exerts a significant influence on the development, invasion, metastasis, and drug resistance of breast cancer. Therefore, this study sought to investigate potential prognostic factors and markers indicative of TME remodeling in breast cancer, utilizing data from the TCGA database.

Methods: In this study, transcriptome RNA-seq data from 1222 breast cancer samples were processed using CIBERSORT and ESTIMATE algorithms.

Surgery challenges and postoperative complications of lung cancer after neoadjuvant immunotherapy.

Background: In China, real-world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited.

Methods: Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine.