Objective:To observe the effect of silicon dioxide (SiO 2) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods:In November 2020, C57BL/6 mice were randomly divided into crystalline SiO 2 group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 μl crystalline SiO 2 suspension (20 mg/ml) or 100 μl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-β (TGF-β) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1β, TNF-α, IL-6, IL-10 and TGF-β were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results:After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO 2 group. Compared with NS group, HYP level of lung tissue in crystalline SiO 2 group were increased, the proportion of M2-typed AMs in crystalline SiO 2 group was increased, the proportion of M1-typed AMs in crystalline SiO 2 group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-β in crystalline SiO 2 group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1β, TNF-α, IL-6 in crystalline SiO 2 group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO 2 group, and the the differences were statistically significant ( P<0.05) . Conclusion:Crystalline SiO 2 may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

Pancreatic cancer,as a common malignant tumor of the digestive system,has a very low survival rate.In recent years,pancreatic cancer has made great progress in diagnostic methods,radiation therapy techniques,and systemic chemotherapy,but its therapeutic effect has not been considerably improved.As a new type of tumor research platform,organoids have made research progress in many fields.Constructing pancreatic cancer organoids is of great research value to guide the individualized treatment of pancreatic cancer.This article reviews the research and clinical application prospect of organoid model in radiotherapy of pancreatic cancer.

Objective:To observe the effect of silicon dioxide (SiO 2) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods:In November 2020, C57BL/6 mice were randomly divided into crystalline SiO 2 group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 μl crystalline SiO 2 suspension (20 mg/ml) or 100 μl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-β (TGF-β) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1β, TNF-α, IL-6, IL-10 and TGF-β were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results:After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO 2 group. Compared with NS group, HYP level of lung tissue in crystalline SiO 2 group were increased, the proportion of M2-typed AMs in crystalline SiO 2 group was increased, the proportion of M1-typed AMs in crystalline SiO 2 group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-β in crystalline SiO 2 group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1β, TNF-α, IL-6 in crystalline SiO 2 group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO 2 group, and the the differences were statistically significant ( P<0.05) . Conclusion:Crystalline SiO 2 may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

Organoids are in vitro-cultured three-dimensional (3D) miniature structures derived from human pluripotent stem cells or adult stem cells from healthy individuals or patients. Compared to traditional two-dimensional (2D) cell lines or animal models, organoids are regarded as more promising high-fidelity models, possessing unique advantages in terms of disease modeling, drug development, the establishment of living biobanks, and the exploration of personalized treatment. Over recent years, the rapid development of organoid technology has brought new hopes for innovating preclinical experimental tumor models and promoting clinical personalized diagnosis and treatment. This review is intended to introduce the development status and latest progress of organoids in the field of radiotherapy for tumors, explore the advantages and limitations of organoid models for cancer, and prospect for its application in the field of radiotherapy.

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*