Error detection for radiotherapy planning validation based on deep learning networks.

BACKGROUND: Quality assurance (QA) of patient-specific treatment plans for intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) necessitates prior validation. However, the standard methodology exhibits deficiencies and lacks sensitivity in the analysis of positional dose distribution data, leading to difficulties in accurately identifying reasons for plan verification failure. This issue complicates and impedes the efficiency of QA tasks. PURPOSE: The primary aim of this research is to utilize deep learning algorithms for the extraction of 3D dose distribution maps and the creation of a predictive model for error classification across multiple machine models, treatment methodologies, and tumor locations. METHOD: We devised five categories of validation plans (normal, gantry error, collimator error, couch error, and dose error), conforming to tolerance limits of different accuracy levels and employing 3D dose distribution data from a sample of 94 tumor patients. A CNN model was then constructed to predict the diverse error types, with predictions compared against the gamma pass rate (GPR) standard employing distinct thresholds (3%, 3 mm; 3%, 2 mm; 2%, 2 mm) to evaluate the model's performance. Furthermore, we appraised the model's robustness by assessing its functionality across diverse accelerators. RESULTS: The accuracy, precision, recall, and F1 scores of CNN model performance were 0.907, 0.925, 0.907, and 0.908, respectively. Meanwhile, the performance on another device is 0.900, 0.918, 0.900, and 0.898. In addition, compared to the GPR method, the CNN model achieved better results in predicting different types of errors. CONCLUSION: When juxtaposed with the GPR methodology, the CNN model exhibits superior predictive capability for classification in the validation of the radiation therapy plan on different devices. By using this model, the plan validation failures can be detected more rapidly and efficiently, minimizing the time required for QA tasks and serving as a valuable adjunct to overcome the constraints of the GPR method.

Triterpenoids with α-glucosidase inhibitory and cytotoxic activities from the fruits of Schisandra chinensis.

An intensive phytochemical investigation into the fruits of Schisandra chinensis afforded 28 triterpenoids incorporating diverse backbones with methyl-migration, ring-expansion and ring-opening features. Among them, ten compounds (1-10) including three likely extracting artefacts (8-10) were described for the first time. Their structures were fully characterized by comprehensive spectroscopic analyses, with the absolute configurations established via electronic circular dichroism and Mosher's NMR techniques. Preliminary biological evaluations revealed that nine isolates showed inhibitory activity against the hyperglycemic target α-glycosidase and 12 compounds exerted cytotoxicity toward three female tumor cell lines (Hela (cervical), MDA-MB231 and MCF-7 (breast)). Compound 6 exhibited the most promising potency on all the three tested cancer cells, and further assessment demonstrated that it could induce significant cell apoptosis and cycle arrest, as well as suppress cell migration, by regulating relevant proteins in MDA-MB231 cells.

Ficolin-A induces macrophage polarization to a novel pro-inflammatory phenotype distinct from classical M1.

BACKGROUND: Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. METHODS: We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. RESULTS: Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. CONCLUSION: Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Effects of gamma-ray irradiation on material and electrical properties of AlN gate dielectric on 4H-SiC.

This article investigates the radiation effects on as-deposited and annealed AlN films on 4H-SiC substrates under gamma-rays. The AlN films are prepared using plasma-enhanced-atomic-layer-deposition on an n-type 4H-SiC substrate. The AlN/4H-SiC MIS structure is subjected to gamma-ray irradiation with total doses of 0, 300, and 600 krad(Si). Physical, chemical, and electrical methods were employed to study the variations in surface morphology, charge transport, and interfacial trapping characteristics induced by irradiation. After 300 krad(Si) irradiation, the as-deposited and annealed samples exhibit their highest root mean square values of 0.917 nm and 1.190 nm, respectively, which is attributed to N vacancy defects induced by irradiation. Under irradiation, the flatband voltage (Vfb) of the as-deposited sample shifts from 2.24 to 0.78 V, while the annealed sample shifts from 1.18 to 2.16 V. X-ray photoelectron spectrum analysis reveals the decomposition of O-related defects in the as-deposited AlN and the formation of Al(NOx)ycompounds in the annealed sample. Furthermore, the space-charge-limits-conduction (SCLC) in the as-deposited sample is enhanced after radiation, while the barrier height of the annealed sample decreases from 1.12 to 0.84 eV, accompanied by the occurrence of the SCLC. The physical mechanism of the degradation of electrical performance in irradiated devices is the introduction of defects like N vacancies and O-related defects like Al(NOx)y. These findings provide valuable insights for SiC power devices in space applications.

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD.

Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD. Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed. Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD. Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD.

Predictive nomogram for 28-day mortality risk in mitral valve disorder patients in the intensive care unit: A comprehensive assessment from the MIMIC-III database.

BACKGROUND: Mitral valve disorder (MVD) stands as the most prevalent valvular heart disease. Presently, a comprehensive clinical index to predict mortality in MVD remains elusive. The aim of our study is to construct and assess a nomogram for predicting the 28-day mortality risk of MVD patients. METHODS: Patients diagnosed with MVD were identified via ICD-9 code from the MIMIC-III database. Independent risk factors were identified utilizing the LASSO method and multivariate logistic regression to construct a nomogram model aimed at predicting the 28-day mortality risk. The nomogram's performance was assessed through various metrics including the area under the curve (AUC), calibration curves, Hosmer-Lemeshow test, integrated discriminant improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: The study encompassed a total of 2771 patients diagnosed with MVD. Logistic regression analysis identified several independent risk factors: age, anion gap, creatinine, glucose, blood urea nitrogen level (BUN), urine output, systolic blood pressure (SBP), respiratory rate, saturation of peripheral oxygen (SpO2), Glasgow Coma Scale score (GCS), and metastatic cancer. These factors were found to independently influence the 28-day mortality risk among patients with MVD. The calibration curve demonstrated adequate calibration of the nomogram. Furthermore, the nomogram exhibited favorable discrimination in both the training and validation cohorts. The calculations of IDI, NRI, and DCA analyses demonstrate that the nomogram model provides a greater net benefit compared to the Simplified Acute Physiology Score II (SAPSII), Acute Physiology Score III (APSIII), and Sequential Organ Failure Assessment (SOFA) scoring systems. CONCLUSION: This study successfully identified independent risk factors for 28-day mortality in patients with MVD. Additionally, a nomogram model was developed to predict mortality, offering potential assistance in enhancing the prognosis for MVD patients. It's helpful in persuading patients to receive early interventional catheterization treatment, for example, transcatheter mitral valve replacement (TMVR), transcatheter mitral valve implantation (TMVI).

Architecting the metabolic reprogramming survival risk framework in LUAD through single-cell landscape analysis: three-stage ensemble learning with genetic algorithm optimization.

Recent studies have increasingly revealed the connection between metabolic reprogramming and tumor progression. However, the specific impact of metabolic reprogramming on inter-patient heterogeneity and prognosis in lung adenocarcinoma (LUAD) still requires further exploration. Here, we introduced a cellular hierarchy framework according to a malignant and metabolic gene set, named malignant & metabolism reprogramming (MMR), to reanalyze 178,739 single-cell reference profiles. Furthermore, we proposed a three-stage ensemble learning pipeline, aided by genetic algorithm (GA), for survival prediction across 9 LUAD cohorts (n = 2066). Throughout the pipeline of developing the three stage-MMR (3 S-MMR) score, double training sets were implemented to avoid over-fitting; the gene-pairing method was utilized to remove batch effect; GA was harnessed to pinpoint the optimal basic learner combination. The novel 3 S-MMR score reflects various aspects of LUAD biology, provides new insights into precision medicine for patients, and may serve as a generalizable predictor of prognosis and immunotherapy response. To facilitate the clinical adoption of the 3 S-MMR score, we developed an easy-to-use web tool for risk scoring as well as therapy stratification in LUAD patients. In summary, we have proposed and validated an ensemble learning model pipeline within the framework of metabolic reprogramming, offering potential insights for LUAD treatment and an effective approach for developing prognostic models for other diseases.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Case Report: ECMO-assisted tracheal reconstruction in a 30-week-gestation preterm infant with tracheal stenosis.

Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination.

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm-2(92% versus 38%,p= 0.01) and 20 mW cm-2(62% versus 15%,p= 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm-2target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm-2target was significantly correlated with measured abscess wall absorption (ρ= 0.7,p= 0.008), but not abscess surface area (ρ= 0.2,p= 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p= 0.0005) and required laser power (p= 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm-2target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as 'Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,' with ClinicalTrials.gov identifier NCT02240498).

IRG1 restrains M2 macrophage polarization and suppresses intrahepatic cholangiocarcinoma progression via the CCL18/STAT3 pathway.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant and aggressive cancer whose incidence and mortality continue to increase, whereas its prognosis remains dismal. Tumor-associated macrophages (TAMs) promote malignant progression and immune microenvironment remodeling through direct contact and secreted mediators. Targeting TAMs has emerged as a promising strategy for ICC treatment. Here, we revealed the potential regulatory function of immune responsive gene 1 (IRG1) in macrophage polarization. We found that IRG1 expression remained at a low level in M2 macrophages. IRG1 overexpression can restrain macrophages from polarizing to the M2 type, which results in inhibition of the proliferation, invasion, and migration of ICC, whereas IRG1 knockdown exerts the opposite effects. Mechanistically, IRG1 inhibited the tumor-promoting chemokine CCL18 and thus suppressed ICC progression by regulating STAT3 phosphorylation. The intervention of IRG1 expression in TAMs may serve as a potential therapeutic target for delaying ICC progression.

SLCO4A1, as a novel prognostic biomarker of non­small cell lung cancer, promotes cell proliferation and migration.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is a membrane transporter protein. The role of this molecule in non­small cell lung cancer (NSCLC) remains unclear. Bulk sequencing was carried out using early­stage NSCLC tissues with lymph node metastasis to identify SLCO4A1 that influences NSCLC cell proliferation, metastasis and prognosis. The in vitro functional assays carried out included the following: Cell Counting Kit­8, plate colony formation, Transwell and wound healing assays. The molecular techniques used included reverse transcription­quantitative PCR, western blotting and immunohistochemistry. The present study revealed the role of SLCO4A in NSCLC. SLCO4A1 was found to be expressed at high levels in NSCLC tissues and cells, and promotes cell proliferation, migration and invasion. Kaplan­Meier survival analysis indicated that patients with NSCLC and high expression of SLCO4A1 had a poor prognosis. SLCO4A was revealed to regulate the expression of the proliferation­related proteins Ki­67 and PCNA, and that of the extracellular matrix proteins vimentin and E­cadherin. Mechanistically, SLCO4A1 may affect the MAPK signaling pathway to promote NSCLC cell proliferation, migration and invasion. In addition, bioinformatics analysis demonstrated a strong association between SLCO4A1 and tumor infiltrating immune cells, highlighting its critical role in immune therapies such as immune checkpoint inhibitor treatment of patients with NSCLC.

MACC: a visual interactive knowledgebase of metabolite-associated cell communications.

Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/.

lncRNA CERS6-AS1 upregulates the expression of ANLN by sponging miR-424-5p to promote the progression and drug resistance of lung adenocarcinoma.

Long non-coding RNAs (lncRNAs) play a crucial role in tumor generation and progression. However, the exact functional significance and underlying molecular mechanism by which lncRNA CERS6-AS1 operates in the context of lung adenocarcinoma (LUAD) remain unknown. We aimed to evaluate the potential role of the CERS6-AS1/miR-424-5p/ANLN axis in the progression of LUAD through bioinformatics and cytobehavioral experiments, and to provide a new insight into the combined treatment of LUAD. Based on the TCGA database, the expression of CERS6-AS1 in pan-cancer was evaluated, and its prognostic performance in LUAD was evaluated by ROC curve, survival curve and COX analysis. In addition, quantification of CERS6-AS1 expression levels in LUAD patients and lung cancer cells using quantitative real-time polymerase chain reaction (RT-qPCR), and further validate the functional significance of CERS6-AS1 in promoting the proliferation, migration, and invasion abilities of lung cancer cells. The competitive endogenous RNA (ceRNA) network was constructed, and miR-424-5p inhibitors were applied to CERS6-AS1 knockdown cells. The potential downstream genes associated with the regulatory axis of CERS6-AS1/miR-424-5p were analyzed by PPI network and gene enrichment analysis (KEGG). Finally, we evaluated the prognostic value of high expression of ANLN in LUAD and its effects on immune cell infiltration, tumor mutation burden, chemotherapy response, and immunotherapy. CERS6-AS1 expression was significantly elevated in both LUAD patients and lung cancer cells. In the CERS6-AS1 knockdown assay, the proliferation, invasion, migration and epithelial-mesenchymal transformation (EMT) of cancer cells were significantly inhibited. Notably, there was a prominent upregulation of miR-424-5p expression in cells where CERS6-AS1 was knocked down. Co-transfection of siRNA and miR-424-5p inhibitors into lung cancer cells restored the restriction on lung cancer cells. Anillin (ANLN) has been identified as a potential target gene for miR-424-5p and as a prognostic and immune biomarker associated with immune cell infiltration and tumor mutational burden in LUAD. Additionally, ANLN impacts the efficacy of chemotherapy and immunotherapy in LUAD patients. This study reveals a novel regulatory mechanism in which CERS6-AS1 may contribute to the progression of LUAD by influencing the expression of ANLN as a competitive sponge for miR-424-5p.

Pluronic F-127 Hydrogel Loaded with Human Adipose-Derived Stem Cell-Derived Exosomes Improve Fat Graft Survival via HIF-1α-Mediated Enhancement of Angiogenesis.

Purpose: Autologous fat grafting is playing an increasingly important role in plastic surgery. However, high absorption and low survival of autologous fat grafts limit their clinical application. This study aimed to investigate whether human adipose-derived stem cell-derived exosomes (hASC-Exos) encapsulated in a PF-127 hydrogel can improve the survival of autologous fat grafts and to elucidate the underlying mechanisms. Patients and Methods: Exosomes were isolated from hASCs and identified using transmission electron microscopy, nanoparticle tracking analysis and Western blotting. We performed functional assays in vitro to assess the effect of hASC-Exos on proliferation, migration, and tube formation as well as their regulatory role in the HIF-1α/VEGF signaling pathway. hASC-Exos encapsulated in the PF-127 hydrogel were used as an in vivo autologous fat graft model. The effects of the PF-127 hydrogel/hASC-Exos and the role of the HIF-1α/VEGF signaling pathway in promoting angiogenesis in an autologous fat grafting model were assessed. Results: hASC-Exos were taken up by human umbilical vein endothelial cells and enhanced their proliferation, migration, and tubule formation in vitro. The effects of hASC-Exos on promoting angiogenesis were mediated by the HIF-1α/VEGF signaling pathway. Moreover, we fabricated a PF-127 hydrogel for the sustained release of hASC-Exos, and in vivo results showed that hASC-Exos encapsulated in PF-127 hydrogel improved the survival of autologous fat grafts. Conclusion: Our findings indicated that hASC-Exos encapsulated in PF-127 hydrogel serve as a key regulator of angiogenesis by activating the HIF-1α/VEGF signaling pathway and provide a promising strategy for autologous fat grafting treatment.

Analysis of Nucleoporin 107 Overexpression and Its Association with Prognosis and Immune Infiltration in Lung Adenocarcinoma by Bioinformatics Methods.

Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated. Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression. Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations. Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.

Case report: Uniportal video-assisted thoracoscopic sleeve lobectomy in a 6-year-old patient with inflammatory myofibroblastic tumor (IMT).

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of "coughing and vomiting for 6 days". A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.

Peptide-Conjugated Micelles Make Effective Mimics of the TRAIL Protein for Driving Apoptosis in Colon Cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) drives apoptosis selectively in cancer cells by clustering death receptors (DR4 and DR5). While it has excellent in vitro selectivity and toxicity, the TRAIL protein has a very low circulation half-life in vivo, which has hampered clinical development. Here, we developed core-cross-linked micelles that present multiple copies of a TRAIL-mimicking peptide at its surface. These micelles successfully induce apoptosis in a colon cancer cell line (COLO205) via DR4/5 clustering. Micelles with a peptide density of 15% (roughly 1 peptide/45 nm2) displayed the strongest activity with an IC50 value of 0.8 µM (relative to peptide), demonstrating that the precise spatial arrangement of ligands imparted by a protein such as a TRAIL may not be necessary for DR4/5/signaling and that a statistical network of monomeric ligands may suffice. As micelles have long circulation half-lives, we propose that this could provide a potential alternative drug to TRAIL and stimulate the use of micelles in other membrane receptor clustering networks.

TMEM147 aggravates the progression of HCC by modulating cholesterol homeostasis, suppressing ferroptosis, and promoting the M2 polarization of tumor-associated macrophages.

BACKGROUND: The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms. METHODS: TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of TMEM147 on the progression of HCC. Proteins interacting with TMEM147 were identified via RNA-seq, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to determine and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Extensive experimental techniques were used to study ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using immunofluorescence assay and flow cytometric analysis. RESULTS: TMEM147 mRNA and protein levels were increased in HCC cells, and the increased TMEM147 expression was associated with a poor survival. TMEM147 promoted tumor cell proliferation and metastases in vitro and in vivo. The protein was found to interact with the key enzyme 7-dehydrocholesterol reductase (DHCR7), which affected cellular cholesterol homeostasis and increased the extracellular levels of 27HC in HCC cells. TMEM147 also promoted the expression of DHCR7 by enhancing the activity of signal transducer and activator of transcription 2. 27HC expression upregulated glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC expression increased the lipid metabolism in macrophages and activated peroxisome proliferator-activated receptor-γ signaling, thereby activating M2 macrophage polarization and promoting HCC cell invasion and migration. CONCLUSIONS: Our results indicate that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. These findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC.