Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the ...underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding protein A14 (S100A14) as a functional regulator suppressing NPC metastasis by inhibiting the NF-kB signaling pathway and reversing the epithelial-mesenchymal transition (EMT). S100A14 was found to be downregulated in highly metastatic NPC cells and tissues. Immunohistochemical staining of 202 NPC samples revealed that lower S100A14 expression was significantly correlated with shorter patient overall survival (OS) and distant metastasis-free survival (DMFS). S100A14 was also found as an independent prognostic factor for favorable survival. Gain- and loss-of-function studies confirmed that S100A14 suppressed the in vitro and in vivo motility of NPC cells. Mechanistically, S100A14 promoted the ubiquitin-proteasome-mediated degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress NPC cellular migration. Moreover, S100A14 and IRAK1 established a feedback loop that could be disrupted by the IRAK1 inhibitor T2457. Overall, our findings showed that the S100A14-IRAK1 feedback loop could be a promising therapeutic target for NPC metastasis.
A photon avalanche (PA) effect that occurs in lanthanide-doped solids gives rise to a giant nonlinear response in the luminescence intensity to the excitation light intensity. As a result, much ...weaker lasers are needed to evoke such PAs than for other nonlinear optical processes. Photon avalanches are mostly restricted to bulk materials and conventionally rely on sophisticated excitation schemes, specific for each individual system. Here we show a universal strategy, based on a migrating photon avalanche (MPA) mechanism, to generate huge optical nonlinearities from various lanthanide emitters located in multilayer core/shell nanostructrues. The core of the MPA nanoparticle, composed of Yb
and Pr
ions, activates avalanche looping cycles, where PAs are synchronously achieved for both Yb
and Pr
ions under 852 nm laser excitation. These nanocrystals exhibit a 26th-order nonlinearity and a clear pumping threshold of 60 kW cm
. In addition, we demonstrate that the avalanching Yb
ions can migrate their optical nonlinear response to other emitters (for example, Ho
and Tm
) located in the outer shell layer, resulting in an even higher-order nonlinearity (up to the 46th for Tm
) due to further cascading multiplicative effects. Our strategy therefore provides a facile route to achieve giant optical nonlinearity in different emitters. Finally, we also demonstrate applicability of MPA emitters to bioimaging, achieving a lateral resolution of ~62 nm using one low-power 852 nm continuous-wave laser beam.
Background
The prognosis of patients who have Epstein‐Barr virus (EBV)‐related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without ...EBV‐related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV‐related NPC by incorporating the measurement of plasma EBV DNA.
Methods
In total, 979 patients with NPC who received intensity‐modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT.
Results
The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression‐free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2‐T3N0 or T1‐T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2‐T3N0 or T1‐T3N1, EBV DNA >2000 copies/mL; T1‐T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1‐T3N2, EBV DNA >2000 copies/mL; T4N0‐N2), and stage RIVA (any T and N3). In the validation cohort, the 5‐year progression‐free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance.
Conclusions
The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV‐related NPC.
The proposed stage groupings incorporating Epstein‐Barr virus DNA by Recursive partitioning analysis have better prognostic performance than the eighth edition American Joint Committee on Cancer/Union for International Cancer Control TNM staging system. Compared with the eighth edition, the proposed stage groupings incorporating Epstein‐Barr virus DNA provide better hazard consistency, hazard discrimination, outcome prediction, and sample size balance
The Tengchong Volcano Field (TVF), located at the southeastern margin of the Tibetan Plateau, is the only Cenozoic volcanic-related geothermal region around the Himalayan geothermal belt that extends ...from southwestern Tibet to western Yunan along the Indo-Asian suture zone. The volcanic rock suites from this field are important proxies for the India-Eurasia convergence since the Late Cretaceous. Here, we investigate the melt inclusions hosted in the Tengchong volcanoes from different locations including Qingliangshan, Heikongshan and Dayingshan based on petrological and geochemical data with a view to gain insights on the magma sources and petrogenesis. Olivine (Ol), clinopyroxene (Cpx), orthopyroxene (Opx) and plagioclase (Pl) phenocrysts from basalts and andesites of the Tengchong volcanic rocks carry abundant melt inclusions. These melt inclusions are high in silica and alkali contents, and enriched in light rare earth elements (LREEs) and large ion lithophile elements (LILEs) such as Rb, Th, U, K, Pb, but depleted in high field strength elements (HFSEs) including Nb, Ta, Ti, P, with arc-like signature. The geochemical features of the melt inclusions suggest that the TVF volcanic rocks are possibly cogenetic, but with a progressive increase in the degree of magma evolution from Qingliangshan, through Heikongshan to Dayingshan. Melt and trace element modeling indicates that the magmas probably originated through variable degrees of partial melting of LREE-enriched upper mantle within garnet stability field with significant contributions from subducted oceanic crust. The melts were contaminated with continental crustal during ascent, followed by fractional crystallization.
The volcanic activity was controlled by major Late Cenozoic dextral strike-slip faults within an extensional setting related to the geodynamic evolution of India plate. Our study provides insights into the tectonics accompanying the India-Eurasia collision.
•Petrological and geochemical features of melt inclusions from Tengchong volcanoes•Geochemical modeling of magma source and origin of the Tengchong volcanic rocks•Tengchong andesites were formed from evolved alkaline basalts through AFC processes•Implications for geodynamic evolution of the India-Eurasia collision belt
We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
What's new?
Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of ...tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.
Optically addressable spin defects in silicon carbide (SiC) have emerged as attractable platforms for various quantum technologies. However, the low photon count rate significantly limits their ...applications. We strongly enhanced the brightness by 7 times and spin-control strength by 14 times of single divacancy defects in 4H-SiC membranes using a surface plasmon generated by gold film coplanar waveguides. The mechanism of the plasmonic-enhanced effect is further studied by tuning the distance between single defects and the surface of the gold film. A three-energy-level model is used to determine the corresponding transition rates consistent with the enhanced brightness of single defects. Lifetime measurements also verified the coupling between defects and surface plasmons. Our scheme is low-cost, without complicated microfabrication and delicate structures, which is applicable for other spin defects in different materials. This work would promote developing spin-defect-based quantum applications in mature SiC materials.
The growth and wetting of water on two-dimensional(2D) materials are important to understand the development of 2D material based electronic, optoelectronic, and nanomechanical devices. Here, we ...visualize the liquefaction processes of water on the surface of graphene, MoS
and black phosphorus (BP) via optical microscopy. We show that the shape of the water droplets forming on the surface of BP, which is anisotropic, is elliptical. In contrast, droplets are rounded when they form on the surface of graphene or MoS
, which do not possess orthometric anisotropy. Molecular simulations show that the anisotropic liquefaction process of water on the surface of BP is attributed to the different binding energies of H
O molecules on BP along the armchair and zigzag directions. The results not only reveal the anisotropic nature of water liquefaction on the BP surface but also provide a way for fast and nondestructive determination of the crystalline orientation of BP.
Background Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node ...positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. Methods We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. Results Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). Conclusions The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy. Keywords: Esophageal neoplasms, Carcinoma Squamous Cell, Tomography X-ray computed, Recurrence, Therapeutics
Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we ...performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio OR = 0.90, 95% CI: 0.87–0.95) and AN (OR = 0.87, 95% CI: 0.77–0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05–1.12; blood-toenail: OR = 1.08, 95% CI: 1.04–1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05–1.17; blood-toenail: OR = 1.13, 95% CI: 1.05–1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.
•Selenium levels were linked to a lower risk of schizophrenia and anorexia nervosa.•Selenium levels were linked to a higher risk of major depressive disorder and autism.•There were no obvious associations between selenium and bipolar disorder and ADHD.
PDF
