Effects of ambient temperature, relative humidity and absolute humidity on risk of nasopharyngeal carcinoma in China.

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi-Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships. Subgroup and interactive analysis were also conducted. Temperature (R2 = 0.68, p < .001), RH (R2 = 0.47, p < .001), and AH (R2 = 0.70, p < .001) exhibited nonlinear correlations with NPC incidence rate. The risk of NPC incidence increased by 20.3% (95% confidence intervals [CI]: [18.9%, 21.7%]) per 1°C increase in temperature, by 6.3% (95% CI: [5.3%, 7.2%]) per 1% increase in RH, and by 32.2% (95% CI: [30.7%, 33.7%]) per 1 g/m3 increase in AH, between their the 25th and the 99th percentiles. In addition, the combination of low temperature and low RH was also related to increased risk (relative risk: 1.60, 95% CI: [1.18, 2.17]). Males and eastern or rural populations tended to be more vulnerable. In summary, this study suggests that ambient temperature, RH, and particularly AH are associated with the risk of NPC incidence.

Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma.

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM's recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.

The Emerging Role of Deubiquitinases in Radiosensitivity.

Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms.

MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature.

Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan-Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.

METTL3-stabilized super enhancers-lncRNA SUCLG2-AS1 mediates the formation of a long-range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma.

BACKGROUND: Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as super-lncRNA, causes the activity of SE to be dysregulated. METHODS: We screened and identified an elevated metastasis-associated SE-lncRNA SUCLG2-AS1 in nasopharyngeal carcinoma (NPC) using RNA-sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and bioinformatics. Western blotting, RT-qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull-down and 3C (chromosome conformation capture assays) were used for mechanistic studies. RESULTS: SUCLG2-AS1 was correlated with a poor prognosis. SUCLG2-AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2-AS1 expression occurred in an m6A-dependent manner. SUCLG2-AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long-range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC. CONCLUSIONS: Taken together, our data suggest that SUCLG2-AS1 may serve as a novel intervention target for the clinical treatment of NPC.

Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy.

In recent years, extracellular vesicles (EVs) have gained significant attention due to their tremendous potential for clinical applications. EVs play a crucial role in various aspects, including tumorigenesis, drug resistance, immune escape, and reconstruction of the tumor microenvironment. Despite the growing interest in EVs, many questions still need to be addressed before they can be practically applied in clinical settings. This paper aims to review EVs' isolation methods, structure research, the roles of EVs in tumorigenesis and their mechanisms in multiple types of tumors, their potential application in drug delivery, and the expectations for their future in clinical research.

Construction of Prognostic Nomogram in Patients with N3-Stage Nasopharyngeal Carcinoma.

INTRODUCTION: The aim of the study was to retrospectively identify the metastatic influence factors and predict the prognosis and develop an individualized prognostic prediction model for patients with N3-stage nasopharyngeal carcinoma (NPC). METHODS: The study collected 446 NPC patients with N3 stage from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The patients were classified into subgroups based on the histological types and metastatic status. Multivariable logistic, Cox regression, and Kaplan-Meier method with the log-rank test were performed. The nomogram model was created using the prognostic factors identified from Cox regression analysis. The predictive accuracy was determined based on the concordance index (c-index) and calibration curves. RESULTS: The 5-year overall survival (OS) of the NPC patients with N3 stage was 43.9%, and the prognosis of patients without any distant metastases was largely longer than that with metastases. No difference was observed between different pathological types in the entire cohort. However, patients with non-keratinized squamous cell carcinoma had a better OS than that of the patients with keratinized squamous cell carcinoma in a nonmetastatic subgroup. Using the Cox regression analysis results, the nomogram successfully classified these patients into low- and high-risk subgroups and presented the survival difference. The c-index of the nomogram for predicting the prognosis was satisfactory. CONCLUSION: This study identified metastatic risk factors and developed a convenient clinical tool for the prognosis of NPC patients. This tool can be used for individualized risk classification and decision-making regarding treatment of NPC patients with N3 stage.

G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells.

Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is a major technological problem in tumor gene therapy. Here, we develop a vector-free gene transfer strategy to deliver genes effectively and selectively by taking advantage of targeting nucleolin. Nucleolin, a shuttle protein moving between cell membrane, cytoplasm and nuclei, is overexpressed in tumor cells. It has a natural ligand G-quadruplex (Gq). Gq-linked DNA (Gq-DNA) is likely to be internalized by ligand dependent uptake mechanisms independently of vectors after neutralizing negative charges of cell membrane by targeting nucleolin. This strategy is referred to as Gq-DNA transfection. Benefiting from its high affinity to nucleolin, Gq-DNA can be effectively delivered into nucleolin-positive tumor cells even nuclei. Gq-DNA transfection is characterized by low cytotoxicity, high efficiency, ease of synthesis, high stability in serum, direct access into nuclei, and specific nucleolin-positive tumor cell targeting.

Identifying nasopharyngeal carcinoma patients with metachronous metastasis sensitive to local treatment: a real-world study.

It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma (NPC) who are sensitive to local treatment of metastases. Here, we aimed to establish a prognostic model for survival and individualize treatments for patients with metastatic NPC. Data were collated from 240 NPC patients diagnosed with metachronous metastasis between 2006 and 2020 who received palliative chemotherapy with or without local treatment. Multivariable Cox regression was implemented to construct a nomogram which had a concordance index of 0.764 when predicting 1-, 3-, and 5-year overall survival (OS). We then classified patients according to risk, creating low- and high-risk groups using the nomogram. Differences in OS between the two groups were significant ( P<0.001). In the low-risk group, the OS for patients who received local treatment was longer than those without ( P=0.009). This novel nomogram shows good performance in classifying patients according to risk and may also be a promising tool for determining who responds best to local treatment. Further validation using external center data is warranted.

Impact of chemotherapy on prognosis of resectable pathological T3N0M0 esophageal cancer patients: a population-based study.

Aims: This study aimed to retrospectively determine the influence factors and survival effects of chemotherapy in pathological T3N0M0 esophageal cancer (EC) patients based on histological type. Methods: A total of 1136 pathological T3N0M0 EC patients who had surgery were chosen from the Surveillance, Epidemiology and End Results database. The patients were divided into subgroups based on histological type and chemotherapy status. Multivariate logistic regression, log-rank test and Cox regression were used to identify prognostic risk factors and survival differences. A propensity score matching analysis was applied to adjust the covariates. The impact of additional chemotherapy was also assessed in patients who had postoperative radiotherapy. Results: The 5-year overall survival was 36.4% for all patients. Chemotherapy was an independent protective factor of survival in both adenocarcinoma and squamous cell carcinoma patients. In the survival analysis, chemotherapy significantly improved the prognosis of EC patients, both for adenocarcinoma and squamous cell carcinoma. Propensity score matching analysis validated these results. Conclusion: Chemotherapy is recommended for pathological T3N0M0 EC patients regardless of histological type.

Lay abstract The prognosis of patients with different histological types of esophageal cancer varies. Chemotherapy is important treatment for these patients. However, the survival benefits of chemotherapy with regard to histological type and clinical stage are unclear. Here the authors used a public database to explore the prognostic value of chemotherapy and survival influence factors in these patients.

Development of an Autophagy Score Signature for Predicting Overall Survival in Papillary Renal Cell Carcinoma.

BACKGROUND: Autophagy is considered to be closely associated with cancer, functioning as either an anticancer or procancer mechanism depending on the cancer stage. However, the prognostic value of autophagy on papillary renal cell carcinoma (pRCC) remains unclear. In this study, our purpose was to determine the autophagy-related mRNA signature to predict the overall survival of patients with pRCC. MATERIALS AND METHODS: A total of 284 patients with pathologic confirmed pRCC in The Cancer Genome Atlas (TCGA) dataset were recruited and included. We choose patients who have smoked less than 15 years but staging 3 or 4 (including nontobacco exposure) vs. more than 15 years but staging 1 or 2. Fourteen differentially expressed mRNAs were found with fold change > 2 and P value < 0.001 through limma package after making a pair between nontobacco exposure or less than 15 years and tobacco exposure more than 15 years by matchIt package. RESULTS: Six mRNAs were identified to be significantly associated with overall survival. Then, using a risk score based on the signature of these six mRNAs, we divided the patients into low-risk and high-risk groups with significantly different OS. Further multivariate Cox regression analyses revealed that the 6-mRNA signature was independent of age, TNM stage, and tumor type. In the present study, a novel 6-mRNA signature that is useful in survival prediction in pRCC patients was developed. If validated, this mRNA signature might assist in selecting high-risk subpopulation that needs more aggressive therapeutic intervention. The risk score involved in several cancer-related pathways was identified using gene set enrichment analysis. CONCLUSION: We initially generated a six autophagy-related genes' signature, which correlates with AJCC N stage, tumor type, and pathological stage and independently predicts OS.

Colorectal Cancer Metastases to Brain or Bone and the Relationship to Primary Tumor Location: a Population-Based Study.

BACKGROUND: The association of primary tumor location with incidence and prognosis of brain or bone metastasis in metastatic colorectal cancer (mCRC) patients remains unclear. We dissect this association across a large population. METHODS: A total of 202,401 CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were included. For brain metastasis, 9478 cases without brain metastasis information were excluded, leaving 192,923 CRC for incidence analysis and multivariable logistic/Cox regression analyses. Similarly, 193,013 CRC were eligible for bone metastasis analyses. RESULTS: The incidence of brain or bone metastasis at initial diagnosis was 1.38% and 6.12% in mCRC cohort, respectively. Median survival of CRC patients with brain or bone metastasis was 4 and 5 months, respectively. Primary tumor location is not associated with the incidence of brain metastasis but with bone metastasis. For bone metastasis, right-sided colon cancer (RCC) patients exhibited the lowest incidence, whereas rectal cancer (RC) patients had the highest. For both brain and bone metastases, RCC patients always had the shortest median survival, whereas RC patients had the longest. The common risk factors for brain or bone metastasis were grade III and multi-extracerebral or ectosteal metastases. The favorable prognostic factors for brain or bone metastasis were being female, married, insured, and RC. RCC is an unfavorable prognostic factor. CONCLUSIONS: Primary tumor location impacts incidence proportions of bone metastasis and survival of both brain and bone mCRC patients. Primary tumor location should be taken into consideration in clinical practice and prognostic assessment.

Incidence and prognosis of pulmonary metastasis in colorectal cancer: a population-based study.

PURPOSE: It is unclear how primary tumor location affects the pulmonary metastasis in colorectal cancer patients with different primary tumor locations. We aim to explore the relationship between primary tumor location and the incidence and prognosis of colorectal cancer patients with pulmonary metastasis at diagnosis. METHODS: From Surveillance, Epidemiology, and End Results (SEER) database, 9920 out of 192,969 CRC patients were identified with pulmonary metastasis at diagnosis between 2010 and 2015. Patients were classified into three subsets according to primary tumor location. The incidence of pulmonary metastasis and median survival were calculated. Multivariable logistic and Cox regression were performed to identify the risk factors of pulmonary metastasis and prognosis. RESULTS: The incidence of pulmonary metastasis was 5.14% in the entire colorectal cancer cohort and 25.66% in metastatic colorectal cancer patients. The median survival of those patients was 10 months. Rectal cancer patients exhibited the highest incidence of pulmonary metastasis, while they had the longest median survival (15 months). The right-sided colon cancer patients had the lowest incidence of pulmonary metastasis, but the shortest median survival (8 months). 61 to 80 years old, over 80, black, two or three extrapulmonary metastatic sites and CEA-positive had a negative influence both on the incidence and prognosis. CONCLUSIONS: The importance of primary tumor location in affecting the incidence of pulmonary metastasis and prognosis of colorectal cancer patients was highlighted in this study. Primary tumor location should be considered in clinical interference and personalized treatment for colorectal cancer patients with pulmonary metastasis.

Analysis of esophageal cancer cell lines exposed to X-ray based on radiosensitivity influence by tumor necrosis factor-α.

Assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of esophageal cancer cell line in vitro. Three esophageal cancer cell line cells were exposed to X-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell growth curve, and flow cytometry was performed to assess the cell apoptosis. The radiosensitizing effects of TNF-α were detected by cell colony formation assay. Western blotting was applied to observe the expression of NF-κB and caspase-3 protein in the exposed cells. Our results indicated that cellular inhibition rate increased over time, the strongest is combined group (P < 0.05). Western blotting showed that the decline expression of NF-κB protein was stated between only rhTNF-α and only X-ray radiation group and the maximum degree was manifested in combined group. Caspase-3 protein content expression just works opposite. Three kinds of cells in the NF-κB protein were similar without rhTNF-α. Then SEG1 NF-κB protein content was reduced more than other two kinds. We concluded that the cells treated with TNF-α showed significantly suppressed cell proliferation, increasing the cell apoptosis, and caspase-3 protein expression after X-ray exposure. TNF-α can enhance the radiosensitivity of esophageal cancer to enhancing the effect of the former.

Nonequilibrium "melting" of a charge density wave insulator via an ultrafast laser pulse.

We employ an exact solution of the simplest model for pump-probe time-resolved photoemission spectroscopy in charge-density-wave systems to show how, in nonequilibrium, the gap in the density of states disappears while the charge density remains modulated, and then the gap reforms after the pulse has passed. This nonequilibrium scenario qualitatively describes the common short-time experimental features in TaS(2) and TbTe(3), indicating a quasiuniversality for nonequilibrium "melting" with qualitative features that can be easily understood within a simple picture.

[The effects of TATA-box in CYC1 promoter on the reporter gene regulated by ERE in the recombinant yeast cell].

The complementary oligonucleotides, each with two consensus estrogen response element (ERE)-sequences and 5'-Hind III and 3'-Sph I sticky ends were artificially synthesized. A solution with both the complementary DNA sequences was heated to 95'C and cooled down to room temperature to form double strand DNA (dsDNA). The set was cloned into the corresponding sites of CYC1 promoter of the pERE-CYC-yEGFP to yield pERE-CYCalpha-yEGFP vector. The two different reporter vectors, pERE-CYC-yEGFP and pERE-CYCalpha-yEGFP, the 2ERE, were placed in the CYC1 promoter. The former promoter downstream ERE contains alpha and beta-TATA boxes and the latter has only alpha-TATA box. The two different reporter vectors were transformed into the yeast cells that express human estrogen receptor alpha (ERalpha). Incubation of the recombinant yeasts with the six estrogenic compounds for 4 hours showed that the recombinant cell containing pERE-CYCalpha-yEGFP would give very poor dose-response curves, in contrast to the recombinant cell containing pERE-CYC-yEGFP which produced well-shaped dose-response curves. So it is necessary for this bioassay that alpha and beta-TATA boxes in the minimal CYC1 promoter when the promoter is used as a rapid and high throughput system for screening estrogenic chemical products.

Evolving network with different edges.

We propose a scale-free network similar to Barabasi-Albert networks but with two different types of edges. This model is based on the idea that in many cases there are more than one kind of link in a network and when a new node enters the network both old nodes and different kinds of links compete to obtain it. The degree distribution of both the total degree and the degree of each type of edge is analyzed and found to be scale-free. Simulations are shown to confirm these results.