Selective SERS Sensing of R6G Molecules Using MoS2 Nanoflowers under Pressure.

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) has garnered significant attention as a subfield of SERS detection due to its capacity to regulate the band gap between molecules and substrates through pressure modulation. Currently, SERS detection primarily focuses on single molecules at atmospheric pressure with limited investigations conducted under high pressure conditions. Herein, we employed rose-shaped MoS2 nanoflowers as the SERS substrate and realized selective PI-SERS enhancement of R6G molecules in the binary (MV+R6G) and ternary (MV+R6G+RhB) systems. The MoS2 demonstrated an exceptionally low SERS detection limit of 5 × 10-6 M in binary and ternary systems with equimolar amounts of molecules. High-pressure experimental results indicate that MoS2 displays selective enhancement for R6G molecules, as evidenced by the comparison of the PI-SERS peak intensity ratio between MoS2 and the probe molecules. The proposed enhancement mechanism in binary and ternary SERS systems under high pressure involves pressure-induced changes in both the band structures of the MoS2 substrate and molecules, thereby influencing their charge transfer dynamics. Consequently, this approach holds great promise for practical applications in complex SERS systems operating under extreme conditions.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p < 0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

[Box: see text].

In Situ Vanadium Modification Induced a Back Interfacial Field Passivation Effect toward Efficient Kesterite Solar Cells beyond 11% Efficiency.

Realization of a high-quality back electrode interface (BEI) with suppressed recombination is crucial for Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. To achieve this goal, the construction of a traditional chemical passivation effect has been widely adopted and investigated. However, there is currently a lack of reports concerning the construction of a field passivation effect (FPE) for the BEI. Herein, considering the characteristic of the negligible difference in ionic radius between Mo (0.65 Å) and V (0.64 Å) as well as the presence of one less valence electron compared to Mo, vanadium (V) was employed and in situ incorporated into the MoSe2 interfacial layer during the deposition of the Mo:V electrode and selenization process. This allowed for the establishment of a desirable in situ VI-FPE interface with p-MoSe2:V/p-CZTSSe at the BEI. The p-type characteristic in MoSe2:V is attributed to the presence of the VMo acceptor; notably, the Fermi energy level of MoSe2:V has shifted downward by 0.62 eV compared to MoSe2, thereby facilitating the formation of an optimized band alignment between MoSe2:V and the absorber. Consequently, the photovoltaic parameters of the cell-FPE have experienced a significant increase due to the enhanced carrier transportation efficiency compared to cell-ref, resulting in a remarkable improvement in efficiency from 8.28 to 11.11%.

LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44.

BACKGROUND: Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear. METHODS: This study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes. RESULTS: Our study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance. CONCLUSIONS: In conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Rosmarinic Acid Alleviates Radiation-Induced Pulmonary Fibrosis by Downregulating the tRNA N7-Methylguanosine Modification-Regulated Fibroblast-to-Myofibroblast Transition Through the Exosome Pathway.

Background: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved. Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation. Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF. Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.

Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study.

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma.

BACKGROUND: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. METHODS: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. RESULTS: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. CONCLUSION: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

Potential predictive value of IVIM MR for xerostomia in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Xerostomia, caused by radiation-induced parotid damage, is the most commonly reported radiotherapy (RT) complication for nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the value of intravoxel incoherent motion (IVIM) MR in monitoring radiation-induced parotid gland damage and predicting the risk of xerostomia. METHODS: Fifty-four NPC patients were enrolled and underwent at least three IVIM MR scans: before (pre-RT), after 5 fractions of (5th-RT), halfway through (mid-RT), and after RT (post-RT). The degree of xerostomia patients was assessed before each MR examination. Furthermore, the time when patients first reported xerostomia symptoms was recorded. The changes in IVIM parameters throughout RT, as well as the relationships between IVIM parameters and xerostomia, were analysed. RESULT: All IVIM parameters increased significantly from pre-RT to post-RT (p < 0.001). The rates of D, D* and f increase increased significantly from pre-RT to mid-RT (p < 0.001), indicating that cell necrosis mainly occurs in the first half of RT. In multivariate analysis, N3 (p = 0.014), pre-D (p = 0.007) and pre-D* (p = 0.003) were independent factors influencing xerostomia. D and f were significantly higher at 5th-RT than at pre-RT (both p < 0.05). IVIM detected parotid gland injury at 5th-RT at an average scanning time of 6.18 ± 1.07 days, earlier than the 11.94 ± 2.61 days when the patient first complained of xerostomia according to the RTOG scale (p < 0.001). CONCLUSIONS: IVIM MR can dynamically monitor radiation-induced parotid gland damage and assess it earlier and more objectively than RTOG toxicity. Moreover, IVIM can screen people at risk of more severe xerostomia early.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

Prognostic value of sarcopenia in the patients with locally advanced nasopharyngeal carcinoma.

PURPOSE: Sarcopenia, characterized by loss of muscle mass index (SMI), serves as a diagnostic indicator for malnutrition and has been shown to influence cancer treatment outcomes. The objective of this study was to investigate the prognostic significance of sarcopenia on the locally advanced nasopharyngeal carcinoma (laNPC) patients. PATIENTS AND METHODS: 545 patients with stage III-IVa NPC were included in this retrospective study. Sarcopenia was defined using the skeletal muscle index (SMI) determined at the C3 level based on baseline MRI. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: The results of the multivariate analysis revealed that sarcopenia group (HR = 2.82, 95% CI 1.96-4.06, P < 0.01), T4 stage (HR = 1.64, 95% CI 1.24-2.15, P < 0.01), N3 stage (HR = 1.91, 95% CI 1.52-2.40, P < 0.01), comorbidities (HR = 2.08, 95% CI 1.45-2.97, P < 0.01), and any adverse event grade 3-4 (HR = 1.48, 95% CI 1.04-2.01, P = 0.03) were identified as independent risk factors that significantly impacted the OS. Additionally, sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), T4 stage (HR = 1.50, 95% CI 1.17-1.92, P < 0.01), N3 stage (HR = 1.80, 95% CI 1.46-2.22, P < 0.01), sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), and any adverse event grade 3-4 (HR = 1.45, 95% CI 1.04-2.01, P = 0.03) were found to have a significant impact on PFS. CONCLUSION: Sarcopenia was identified as a prognostic factor for patients with laNPC. Furthermore, T stage, N stage, comorbidities, and any adverse event grade 3-4 were identified as independent prognostic factors for laNPC.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy. MATERIALS AND METHODS: The observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed. RESULTS: Moderate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS. CONCLUSION: Radiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

Machine learning-based identification of a consensus immune-derived gene signature to improve head and neck squamous cell carcinoma therapy and outcome.

Background: Head and neck squamous cell carcinoma (HNSCC), an extremely aggressive tumor, is often associated with poor outcomes. The standard anatomy-based tumor-node-metastasis staging system does not satisfy the requirements for screening treatment-sensitive patients. Thus, an ideal biomarker leading to precise screening and treatment of HNSCC is urgently needed. Methods: Ten machine learning algorithms-Lasso, Ridge, stepwise Cox, CoxBoost, elastic network (Enet), partial least squares regression for Cox (plsRcox), random survival forest (RSF), generalized boosted regression modelling (GBM), supervised principal components (SuperPC), and survival support vector machine (survival-SVM)-as well as 85 algorithm combinations were applied to construct and identify a consensus immune-derived gene signature (CIDGS). Results: Based on the expression profiles of three cohorts comprising 719 patients with HNSCC, we identified 236 consensus prognostic genes, which were then filtered into a CIDGS, using the 10 machine learning algorithms and 85 algorithm combinations. The results of a study involving a training cohort, two testing cohorts, and a meta-cohort consistently demonstrated that CIDGS was capable of accurately predicting prognoses for HNSCC. Incorporation of several core clinical features and 51 previously reported signatures, enhanced the predictive capacity of the CIDGS to a level which was markedly superior to that of other signatures. Notably, patients with low CIDGS displayed fewer genomic alterations and higher immune cell infiltrate levels, as well as increased sensitivity to immunotherapy and other therapeutic agents, in addition to receiving better prognoses. The survival times of HNSCC patients with high CIDGS, in particular, were shorter. Moreover, CIDGS enabled accurate stratification of the response to immunotherapy and prognoses for bladder cancer. Niclosamide and ruxolitinib showed potential as therapeutic agents in HNSCC patients with high CIDGS. Conclusion: CIDGS may be used for stratifying risks as well as for predicting the outcome of patients with HNSCC in a clinical setting.

Knockdown of hCINAP sensitizes colorectal cancer cells to ionizing radiation.

Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure. Subsequent analysis revealed a notable increase in hCINAP expression in radiation-resistant CRC cells. To elucidate the functional role of hCINAP in radio-resistance, knockdown experiments were conducted. Remarkably, knockdown of hCINAP resulted in an elevation of reactive oxygen species (ROS) generation upon radiation treatment and subsequent activation of apoptosis mediated by mitochondria. These observations indicate that hCINAP depletion enhances the radiosensitivity of CRC cells. Conversely, when hCINAP was overexpressed, it was found to enhance the radio-resistance of CRC cells. This suggests that elevated hCINAP expression contributes to the development of radio-resistance. Further investigation revealed an interaction between hCINAP and ATPase family AAA domain containing 3A (ATAD3A). Importantly, ATAD3A was identified as an essential factor in hCINAP-mediated radio-resistance. These findings establish the involvement of hCINAP and its interaction with ATAD3A in the regulation of radio-resistance in CRC cells. Overall, the results of this study demonstrate that upregulating hCINAP expression may improve the survival of radiation-exposed CRC cells. Understanding the intricate molecular mechanisms underlying hCINAP function holds promise for potential strategies in targeted radiation therapy for CRC. These findings emphasize the importance of further research to gain a comprehensive understanding of hCINAP's precise molecular mechanisms and explore its potential as a therapeutic target in overcoming radio-resistance in CRC. By unraveling the complexities of hCINAP and its interactions, novel therapeutic approaches may be developed to enhance the efficacy of radiation therapy and improve outcomes for CRC patients.

Ferroptosis-Related Genes Are Associated with Radioresistance and Immune Suppression in Head and Neck Cancer.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

OBJECTIVE: Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. RESULTS: The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. CONCLUSION: The SII-PNI score is a reliable and convenient indicator for predicting sRIOM in patients with LANPC.

Selection of reference genes in liproxstatin-1-treated K562 Leukemia cells via RT-qPCR and RNA sequencing.

BACKGROUND: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) can accurately detect relative gene expression levels in biological samples. However, widely used reference genes exhibit unstable expression under certain conditions. METHODS AND RESULTS: Here, we compared the expression stability of eight reference genes (RPLP0, RPS18, RPL13, EEF1A1, ß-actin, GAPDH, HPRT1, and TUBB) commonly used in liproxstatin-1 (Lip-1)-treated K562 cells using RNA-sequencing and RT-qPCR. The expression of EEF1A1, ACTB, GAPDH, HPRT1, and TUBB was considerably lower in cells treated with 20 µM Lip-1 than in the control, and GAPDH also showed significant downregulation in the 10 µM Lip-1 group. Meanwhile, when we used geNorm, NormFinder, and BestKeeper to compare expression stability, we found that GAPDH and HPRT1 were the most unstable reference genes among all those tested. Stability analysis yielded very similar results when geNorm or BestKeeper was used but not when NormFinder was used. Specifically, geNorm and BestKeeper identified RPL13 and RPLP0 as the most stable genes under 20 µM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable under 10 µM Lip-1 treatment. TUBB and EEF1A1 were the most stable genes in both treatment groups according to the results obtained using NormFinder. An assumed most stable gene was incorporated into each software to validate the accuracy. The results suggest that NormFinder is not an appropriate algorithm for this study. CONCLUSIONS: Stable reference genes were recognized using geNorm and BestKeeper but not NormFinder. Overall, RPL13 and RPLP0 were the most stable reference genes under 20 µM Lip-1 treatment, whereas RPL13, EEF1A1, and TUBB were the most stable genes under 10 µM Lip-1 treatment.

Resonance-Assisted Surface-Enhanced Raman Spectroscopy Amplification on Hierarchical Rose-Shaped MoS2/Au Nanocomposites.

Surface-enhanced Raman spectroscopy (SERS) has emerged as a highly sensitive trace detection technique in recent decades, yet its exceptional performance remains elusive in semiconductor materials due to the intricate and ambiguous nature of the SERS mechanism. Herein, we have synthesized MoS2 nanoflowers (NFs) decorated with Au nanoparticles (NPs) by hydrothermal and redox methods to explore the size-dependence SERS effect. This strategy enhances the interactions between the substrate and molecules, resulting in exceptional uniformity and reproducibility. Compared to the unadorned Au nanoparticles (NPs), the decoration of Au NPs induces an n-type effect on MoS2, resulting in a significant enhancement of the SERS effect. This augmentation empowers MoS2 to achieve a low limit of detection concentration of 2.1 × 10-9 M for crystal violet (CV) molecules and the enhancement factor (EF) is about 8.52 × 106. The time-stability for a duration of 20 days was carried out, revealing that the Raman intensity of CV on the MoS2/Au-6 substrate only exhibited a reduction of 24.36% after undergoing aging for 20 days. The proposed mechanism for SERS primarily stems from the synergistic interplay among the resonance of CV molecules, local surface plasma resonance (LSPR) of Au NPs, and the dual-step charge transfer enhancement. This research offers comprehensive insights into SERS enhancement and provides guidance for the molecular design of highly sensitive SERS systems.