Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Long noncoding RNA TMPO-AS1 upregulates BCAT1 expression to promote cell proliferation in nasopharyngeal carcinoma via microRNA let-7c-5p.

BACKGROUND: Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal carcinoma (NPC) is an epithelial tumor that occurs in the nasopharynx and is common in North Africa and Southeast Asia. The study investigated the functions of lncRNA TMPO-AS1 in NPC cell proliferation and apoptosis as well as its related competing endogenous RNA (ceRNA) mechanism. METHODS: Candidate microRNA and genes that may regulated by TMPO-AS1 were predicted with the bioinformatic tool starBase. TMPO-AS1 expression in NPC tissue, cells, nuclear part, and cytoplasmic part was measured by RT-qPCR. MTT assay, EdU assay, and flow cytometry analysis were carried out to evaluate NPC cell viability, proliferation, and apoptosis, respectively. RNA immunoprecipitation assay and luciferase reporter assay were conducted to detect the binding between TMPO-AS1 and let-7c-5p or that between let-7c-5p and BCAT1. RESULTS: TMPO-AS1 and BCAT1 showed high expression in NPC tissue and cells, while let-7c-5p was downregulated in NPC. The silencing of TMPO-AS1 suppressed NPC cell proliferation while promoting cell apoptosis. Moreover, TMPO-AS1 interacted with let-7c-5p and negatively regulated let-7c-5p expression. BCAT1 was a target of let-7c-5p and was inversely regulated by let-7c-5p in NPC cells. The repressive impact of TMPO-AS1 knockdown on NPC cell growth was countervailed by overexpressed BCAT1. CONCLUSION: TMPO-AS1 accelerates NPC cell proliferation and represses cell apoptosis by interacting with let-7c-5p to regulate BCAT1 expression.

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Efficacy of simple and very brief handgrip and isometric exercises for reducing withdrawal symptoms in cigarette smokers: A pilot randomized controlled trial.

INTRODUCTION: Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). METHODS: In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were self-reported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen's f2 (small=0.02, medium=0.15, large=0.35). RESULTS: Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen's f2=0.54, 95% CI: 0.52-0.57), QSU-B (Cohen's f2=0.77; 95% CI: 0.74-0.80), and MPSS (Cohen's f2=0.51; 95% CI: 0.46-0.56) over the three measurement points. CONCLUSIONS: This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/. IDENTIFIER: NCT04059497.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

Albumin-to-fibrinogen ratio is an independent prognostic parameter in de novo non-M3 acute myeloid leukemia.

Inflammation and nutrition related proteins participate in the development of acute myeloid leukemia (AML). It has been reported that the albumin-to-fibrinogen ratio (AFR) could serve as a prognostic indicator in patients with malignancy, but the precise relevance of AML is unclear. This study aimed to evaluate the effect of AFR on survival prognosis in patients with AML. We analyzed 227 patients newly diagnosed with non-M3 AML. AFR was calculated as albumin divided by fibrinogen. Based on the cutoff point from X-tile program, patients were divided into AFR-high (38.8%) and AFR-low (61.2%) groups. AFR-low group showed a poorer complete remission rate (P < 0.001) and median time to relapse (P = 0.026), while the mortality was higher (P = 0.009) than AFR-high ones. According to the log-rank test, AFR-low group had shorter OS (P < 0.001) and DFS (P = 0.034). Multivariate analysis identified AFR, ELN risk, bone marrow transplant, and hemoglobin as independent prognostic variables associated with OS. A visualized nomogram for predicting OS was performed. The C-index (0.75), calibration plots, and decision curve analyses of new model showed better discrimination, calibration, and net benefits than the ELN risk model. The time-dependent receiver operating characteristic (ROC) curve of 1-, 2-, and 3-year also functioned well (AUC, 0.81, 0.93 and 0.90, respectively). Our study provided a comprehensive view of AFR which could be an independent prognostic indicator in AML patients. The prognostic model utilized readily available information from ordinary clinical practice to improve predictive performance, identify risks, and assist in therapeutic decision-making.

Taste alterations in patients following hematopoietic stem cell transplantation: A qualitative study.

Objective: This study aims to explore the experiences and consequences of taste alterations in patients undergoing HSCT, how they respond to these changes, and the factors that influence their responses. Methods: In this descriptive qualitative study, face-to-face semi-structured individual interviews were conducted with 31 patients undergoing HSCT in a comprehensive hospital in Hubei, China. The interview data were transcribed and analyzed using Colaizzi's seven-step analysis. The Symptom Management Theory was applied to design the study and identify key themes. Results: Three key themes were identified from the theory: (1) the complexity and diversity of taste experiences; (2) coping strategies; and (3) the multifaceted challenges of coping. Taste alterations in HSCT patients were characterized by diversity and dynamism. Patients employed three distinct coping styles in response to taste alterations: active coping, reluctant submission, and passive coping. These coping styles were influenced by various factors, including the specific treatment modalities of HSCT, individual patient characteristics, and the healthcare environment. Conclusions: The experience of taste alterations among HSCT patients is intricate and varied, and the importance of addressing this symptom can easily be underestimated. Management of taste alterations is influenced by multiple factors. Nursing staff should give careful attention to taste alterations in HSCT survivors, enhance their expertise in managing taste alterations, provide robust health education, conduct regular screening and assessments, and formulate individualized intervention plans to assist patients in actively and effectively managing taste alterations.

Physically cross-linked organo-hydrogels for friction interfaces in joint replacements: design, evaluation and potential clinical applications.

This paper investigates physically crosslinked organo-hydrogels for total hip replacement surgery. Current materials in artificial joints have limitations in mechanical performance and biocompatibility. To overcome these issues, a new approach based on hydrogen bonds between polyvinyl alcohol, poly(2-hydroxyethyl methacrylate), and glycerin is proposed to develop bioactive organo-hydrogels with improved mechanical properties and biocompatibility. This study analyzes local pathological characteristics, systemic toxicity, and mechanical properties of the gels. The results show that the gels possess excellent biocompatibility and mechanical strength, suggesting their potential as an alternative material for total hip replacement surgery. These findings contribute to improving patient outcomes in joint replacement procedures.

Identification and validation of novel biomarkers associated with immune infiltration for the diagnosis of osteosarcoma based on machine learning.

Objectives: Osteosarcoma is the most common primary malignant tumor in children and adolescents, and the 5-year survival of osteosarcoma patients gained no substantial improvement over the past decades. Effective biomarkers in diagnosing osteosarcoma are warranted to be developed. This study aims to explore novel biomarkers correlated with immune cell infiltration in the development and diagnosis of osteosarcoma. Methods: Three datasets (GSE19276, GSE36001, GSE126209) comprising osteosarcoma samples were extracted from Gene Expression Omnibus (GEO) database and merged to obtain the gene expression. Then, differentially expressed genes (DEGs) were identified by limma and potential biological functions and downstream pathways enrichment analysis of DEGs was performed. The machine learning algorithms LASSO regression model and SVM-RFE (support vector machine-recursive feature elimination) analysis were employed to identify candidate hub genes for diagnosing patients with osteosarcoma. Receiver operating characteristic (ROC) curves were developed to evaluate the discriminatory abilities of these candidates in both training and test sets. Furthermore, the characteristics of immune cell infiltration in osteosarcoma, and the correlations between these potential genes and immune cell abundance were illustrated using CIBERSORT. qRT-PCR and western blots were conducted to validate the expression of diagnostic candidates. Results: GEO datasets were divided into the training (merged GSE19276, GSE36001) and test (GSE126209) groups. A total of 71 DEGs were screened out in the training set, including 10 upregulated genes and 61 downregulated genes. These DEGs were primarily enriched in immune-related biological functions and signaling pathways. After machine learning by SVM-RFE and LASSO regression model, four biomarkers were chosen for the diagnostic nomogram for osteosarcoma, including ASNS, CD70, SRGN, and TRIB3. These diagnostic biomarkers all possessed high diagnostic values (AUC ranging from 0.900 to 0.955). Furthermore, these genes were significantly correlated with the infiltration of several immune cells, such as monocytes, macrophages M0, and neutrophils. Conclusion: Four immune-related candidate hub genes (ASNS, CD70, SRGN, TRIB3) with high diagnostic value were confirmed for osteosarcoma patients. These diagnostic genes were significantly connected with the immune cell abundance, suggesting their critical roles in the osteosarcoma tumor immune microenvironment. Our study provides highlights on novel diagnostic candidate genes with high accuracy for diagnosing osteosarcoma patients.

Effectiveness of personalized smoking cessation intervention based on ecological momentary assessment for smokers who prefer unaided quitting: protocol for a randomized controlled trial.

Introduction: Ecological momentary assessment (EMA)-based smoking cessation intervention may help personalize intervention for smokers who prefer to quit smoking unaided. This study aims to evaluate the effectiveness of EMA-based phone counseling and instant messaging for smoking cessation. Methods/design: This is a two-arm, accessor-blinded, simple individual randomized controlled trial (allocation ratio 1:1). Participants will be recruited from community sites and online platforms in Hong Kong. Interventions will be delivered via a phone call and instant messaging. Current adult smokers who (1) self-report no intention to use smoking cessation services and medication in the coming month and (2) have not used smoking cessation services or nicotine replacement therapy in the past 7 days will be recruited. Recruited participants will be randomized to intervention or control groups via an online randomizer. All participants will be required to complete EMAs (five times per day for 7 consecutive days). The intervention group (n = 220) will receive a nurse-led brief phone counseling immediately after the 1-week EMAs and 10-week EMA-based advice via instant messaging applications (e.g., WhatsApp, WeChat). The 10-week EMA-based advice covers a summary of the 1-week EMAs, and tailored cessation support focused on personalized smoking triggers. The control group (n = 220) will not receive any intervention during the same period. The primary outcomes are participants' progression toward smoking cessation assessed by the Incremental Behavior Change toward Smoking Cessation (IBC-S) and biochemically validated abstinence at the 3-month follow-up. Secondary outcomes include self-reported and biochemically validated tobacco abstinence at the 6-month follow-up. Discussion: The findings will provide evidence that the EMA-based tailored smoking cessation intervention can be adapted as a new health promotion strategy for current smokers who are unwilling to use smoking cessation aids. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT05212220, identifier: NCT05212220.

Endovascular treatment for massive haemoptysis due to pulmonary pseudoaneurysm: report of 23 cases.

PURPOSE: To evaluate the safety and effectiveness of endovascular treatment for massive haemoptysis caused by pulmonary pseudoaneurysm (PAP). METHODS: The clinical data, imaging data, and endovascular treatment protocol of 23 patients with massive haemoptysis caused by continuous PAP were retrospectively analysed. The success, complications, postoperative recurrence rate, and influence of the treatment on pulmonary artery pressure were also evaluated. RESULTS: Nineteen patients with a bronchial artery-pulmonary artery (BA-PA) and/or nonbronchial systemic artery-pulmonary artery (NBSA-PA) fistula underwent bronchial artery embolization (BAE) and/or nonbronchial systemic artery embolization (NBSAE) + pulmonary artery embolization (PAE). The pulmonary artery (PA) pressures before and after embolization were 52.11 ± 2.12 (35-69 cmH2O) and 33.58 ± 1.63 (22-44 cmH2O), respectively (P = 0.001). Four patients did not have a BA-PA and/or NBSA-PA fistula. Embolization was performed in two patients with a distal PAP of the pulmonalis lobar arteria. Bare stent-assisted microcoils embolization was performed in the other two patients with a PAP of the main pulmonary lobar arteries. The PA pressures of the four patients before and after treatment were 24.50 ± 1.32 (22-28 cmH2O) and 24.75 ± 1.70 (22-29 cmH2O), respectively (P = 0.850). The technique had a 100% success rate with no serious complications and a postoperative recurrence rate of 30%. CONCLUSION: Endovascular treatment is safe and effective for massive haemoptysis caused by PAP. BAE and/or NBSAE can effectively reduce pulmonary hypertension in patients with a BA-PA and/or NBSA-PA fistula.

A novel tumor microenvironment-related gene signature with immune features for prognosis of lung squamous cell carcinoma.

PURPOSE: Lung squamous cell carcinoma (LUSC) is an aggressive subset of non-small-cell lung cancer (NSCLC). The tumor microenvironment (TME) plays an important role in the development of LUSC. We aim to identify potential therapeutic targets and a TME-related prognostic signature and for LUSC. METHODS: TME-related genes were obtained from TCGA-LUSC dataset. LUSC samples were clustered by the non-negative matrix clustering algorithm (NMF). The prognostic signature was constructed through univariate Cox regression, multivariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) analyses. Gene set enrichment analysis (GSEA) was carried out to explore the enrichment pathways. RESULTS: This study constructed a prognostic signature which contained 12 genes: HHIPL2, PLK4, SLC6A4, LSM1, TSLP, P4HA1, AMH, CLDN5, NRTN, CDH2, PTGIS, and STX1A. Patients were classified into high-risk and low-risk groups according to the median risk score of this signature. Compared with low-risk group patients, patients in high-risk group patients had poorer overall survival, which demonstrated this signature was an independent prognostic factor. Besides, correlation analysis and GSEA results revealed that genes of this signature were correlated with immune cells and drug response. CONCLUSION: Our novel signature based on 12 TME-related genes might be applied as an independent prognostic indicator. Importantly, the signature could be a promising biomarker and accurately predict the prognosis of LUSC patients.

A Comprehensive Review of Pea (Pisum sativum L.): Chemical Composition, Processing, Health Benefits, and Food Applications.

Pisum sativum L., commonly referred to as dry, green, or field pea, is one of the most common legumes that is popular and economically important. Due to its richness in a variety of nutritional and bioactive ingredients, the consumption of pea has been suggested to be associated with a wide range of health benefits, and there has been increasing focus on its potential as a functional food. However, there have been limited literature reviews concerning the bioactive compounds, health-promoting effects, and potential applications of pea up to now. This review, therefore, summarizes the literature from the last ten years regarding the chemical composition, physicochemical properties, processing, health benefits, and potential applications of pea. Whole peas are rich in macronutrients, including proteins, starches, dietary fiber, and non-starch polysaccharides. In addition, polyphenols, especially flavonoids and phenolic acids, are important bioactive ingredients that are mainly distributed in the pea coats. Anti-nutritional factors, such as phytic acid, lectin, and trypsin inhibitors, may hinder nutrient absorption. Whole pea seeds can be processed by different techniques such as drying, milling, soaking, and cooking to improve their functional properties. In addition, physicochemical and functional properties of pea starches and pea proteins can be improved by chemical, physical, enzymatic, and combined modification methods. Owing to the multiple bioactive ingredients in peas, the pea and its products exhibit various health benefits, such as antioxidant, anti-inflammatory, antimicrobial, anti-renal fibrosis, and regulation of metabolic syndrome effects. Peas have been processed into various products such as pea beverages, germinated pea products, pea flour-incorporated products, pea-based meat alternatives, and encapsulation and packing materials. Furthermore, recommendations are also provided on how to better utilize peas to promote their development as a sustainable and functional grain. Pea and its components can be further developed into more valuable and nutritious products.

Biodegradable NIR-II Pseudo Conjugate Polymeric Nanoparticles Amplify Photodynamic Immunotherapy via Alleviation of Tumor Hypoxia and Tumor-Associated Macrophage Reprogramming.

Photodynamic therapy (PDT) has achieved great success in cancer treatment. Despite its great promise, the efficacy of photodynamic immunotherapy can be limited by the hypoxia in solid tumors which is closely related to the abnormal tumor vasculature. These abnormal vasculatures are a hallmark of most solid tumors and facilitate immune evasion. Therefore, tumor vascular normalization is developed as a promising strategy to overcome tumor hypoxia, resulting in improved cancer therapy. Here, a NIR-II bio-degradable pseudo-conjugate polymer (PSP)-based photodynamic polymer is designed to deliver a vascular normalization agent, i.e., regorafenib (Reg) in nanoparticles (NP-PDT@Reg). NP-PDT@Reg under 808 nm laser irradiation (NP-PDT@Reg + L) can efficiently release Reg to improve the tumor hypoxia via vascular normalization, making more NP-PDT@Reg and oxygen enter the tumors. Moreover, NP-PDT@Reg + L can further result in generation of more reactive oxygen species (ROS) to eradicate tumor cells while inducing immunogenic cell death (ICD) to activate anti-tumor immune responses. In addition, Reg can reprogram TAM from a pro-tumor M2 phenotype to a tumor-killing M1 phenotype as well, thereby reversing the immunosuppressive tumor microenvironment. Taken together, the current study provides an innovative perspective on the development of novel nanomaterials to overcome the limitations in photodynamic immunotherapy.

The increased expression of cytokeratin 13 leads to an increase in radiosensitivity of nasopharyngeal carcinoma HNE-3 cells by upregulating ERRFI1.

The main factors contributing to the unfavorable outcome in the clinical treatment of patients with nasopharyngeal carcinoma (NPC) patients are radiation resistance and recurrence. This study aimed to investigate the sensitivity and molecular foundation of cytokeratin 13 (CK13) in the radiotherapy of NPC. To achieve this, a human NPC cell line overexpressing CK13, HNE-3-CK13, was constructed. The effects of CK13 overexpression on cell viability and apoptosis under radiotherapy conditions were evaluated using the CCK-8 assay, immunofluorescence, and western blotting (WB). Next-generation sequencing was performed to identify the downstream genes and signaling pathways of CK13 that mediate radiotherapy response. The potential role of the candidate gene ERRFI1 in CK13-induced enhancement of radiosensitivity was investigated through rescue experiments using clone formation and WB. The effects of ERRFI1 on cell viability, cell apoptosis, cell cycle, and the related key genes were further evaluated using CCK-8, immunofluorescence, flow cytometry, quantitative polymerase chain reaction and WB. The results showed that CK13 overexpression in HNE-3 significantly inhibited cell survival under radiotherapy and promoted apoptosis marker γH2AX expression, leading to a significant increase of ERRFI1. Knockdown of ERRFI1 rescued the decreased cell viability and proliferation and the increased cell apoptosis that were caused by CK13 overexpression-mediated radiotherapy sensitization of NPC cells. In this process, EGFR, AKT, and GSK-3ß were found involved. In the end, ERRFI1 was proven to inhibit expression levels of CDK1, CDK2, cyclin B1, and cyclin D1, resulting an increased G2/M cell ratio. Overexpression of CK13 enhances the radiosensitivity of NPC cells, which is characterized by decreased cell viability and proliferation and increased apoptosis. This regulation may affect the survival of HNE-3 cells by increasing the expression of ERRFI1 and activating the EGFR/Akt/GSK-3ß signaling pathway, providing new potential therapeutic targets for the treatment of NPC.