Segmented Control of Selenization Environment for High-Quality Cu2ZnSn(S,Se)4 Films Toward Efficient Kesterite Solar Cells.

High-crystalline-quality absorbers with fewer defects are crucial for further improvement of open-circuit voltage (VOC) and efficiency of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. However, the preparation of high-quality CZTSSe absorbers remains challenging due to the uncontrollability of the selenization reaction and the complexity of the required selenization environment for film growth. Herein, a novel segmented control strategy for the selenization environment, specifically targeting the evaporation area of Se, to regulate the selenization reactions and improve the absorber quality is proposed. The large evaporation area of Se in the initial stage of the selenization provides a great evaporation and diffusion flux for Se, which facilitates rapid phase transition reactions and enables the attainment of a single-layer thin film. The reduced evaporation area of Se in the later stage creates a soft-selenization environment for grain growth, effectively suppressing the loss of Sn and promoting element homogenization. Consequently, the mitigation of Sn-related deep-level defects on the surface and in the bulk induced by element imbalance is simultaneously achieved. This leads to a significant improvement in nonradiative recombination suppression and carrier collection enhancement, thereby enhancing the VOC. As a result, the CZTSSe device delivers an impressive efficiency of 13.77% with a low VOC deficit.

Passivating Grain Boundaries via Graphene Additive for Efficient Kesterite Solar Cells.

Grain boundaries (GBs)-triggered severe non-radiative recombination is recently recognized as the main culprits for carrier loss in polycrystalline kesterite photovoltaic devices. Accordingly, further optimization of kesterite-based thin film solar cells critically depends on passivating the grain interfaces of polycrystalline Cu2 ZnSn(S,Se)4 (CZTSSe) thin films. Herein, 2D material of graphene is first chosen as a passivator to improve the detrimental GBs. By adding graphene dispersion to the CZTSSe precursor solution, single-layer graphene is successfully introduced into the GBs of CZTSSe absorber. Due to the high carrier mobility and electrical conductivity of graphene, GBs in the CZTSSe films are transforming into electrically benign and do not act as high recombination sites for carrier. Consequently, benefitting from the significant passivation effect of GBs, the use of 0.05 wt% graphene additives increases the efficiency of CZTSSe solar cells from 10.40% to 12.90%, one of the highest for this type of cells. These results demonstrate a new route to further increase kesterite-based solar cell efficiency by additive engineering.

2D Ti3C2-MXene Serving as Intermediate Layer between Absorber and Back Contact for Efficient CZTSSe Solar Cells.

Kesterite Cu2ZnSn(S,Se)4 (CZTSSe) has been considered as the most promising absorber material for inorganic thin-film solar cells. Among the three main interfaces in CZTSSe-based solar cells, the CZTSSe/Mo back interface plays an essential role in hole extraction as well as device performance. During the selenization process, the reaction between CZTSSe and Mo is one of the main reasons that lead to a large open circuit voltage (VOC) deficit, low short circuit current (Jsc), and fill factor. In this study, 2D Ti3C2-MXene was introduced as an intermediate layer to optimize the interface between the CZTSSe absorber layer and Mo back contact. Benefiting from the 2D Ti3C2-MXene intermediate layer, the reaction between CZTSSe and Mo was effectually suppressed, thus, significantly reducing the thickness of the detrimental Mo(S,Se)2 layer as well as interface recombination at the CZTSSe/Mo back interface. As a result, the power conversion efficiency of the champion device fabricated with the 2D Ti3C2-MXene intermediate layer was improved from 10.89 to 13.14% (active-area efficiency). This study demonstrates the potential use of the 2D Ti3C2-MXene intermediate layer for efficient CZTSSe solar cells and promotes a deeper understanding of the back interface in CZTSSe solar cells.

Progress and prospectives of solution-processed kesterite absorbers for photovoltaic applications.

Solar cells based on emerging kesterite Cu2ZnSn(S,Se)4 (CZTSSe) materials have reached certified power conversion efficiency (PCE) as high as 13.6%, showing great potential in the next generation of photovoltaic technologies because of their earth-abundant, tunable direct bandgap, high optical absorption coefficient, environment-friendly, and low-cost properties. The predecessor of CZTSSe is Cu(In,Ga) Se2 (CIGS), and the highest PCE of CIGS fabricated by the vacuum method is 23.35%. However, the recorded PCE of CZTSSe devices are fabricated by a low-cost solution method. The characteristics of the solvent play a key role in determining the crystallization kinetics, crystal growth quality, and optoelectronic properties of the CZTSSe thin films in the solution method. It is still challenging to improve the efficiency of CZTSSe solar cells for future commercialization and applications. This review describes the current status of CZTSSe solar cell absorbers fabricated by protic solvents with NH (hydrazine), protic solvents with SH (amine-thiol), aprotic solvents (DMSO and DMF), ethylene glycol methyl ether-based precursor solution method (EGME), and thioglycolic acid (TGA)-ammonia solution (NH3H2O) deposition methods. Furthermore, the performances of vacuum-deposited devices and solution-based processed devices are compared. Finally, the challenges and outlooks of CZTSSe solar cells are discussed for further performance improvement.

LINC00886 Negatively Regulates Malignancy in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify specific long noncoding RNAs (lncRNAs) associated with ATC, and further investigated their biological functions and molecular mechanism underlying regulation of malignancy in ATC. We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a potential biomarker in thyroid cancer patients from the FUSCC, GEO, and The Cancer Genome Atlas, which was then investigated for its functional roles and molecular mechanism in ATC in vitro. The clinicopathological association analyses revealed that LINC00886 expression was significantly correlated with dedifferentiation and suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through the ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by downregulation of LINC00886 enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing phosphorylation of eIF2α and thus promoted protein synthesis to maintain ATC malignancy. Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that LINC00886/PKR/eIF2α signaling is a potential therapeutic target in ATC.

Influenza surveillance with Baidu index and attention-based long short-term memory model.

BACKGROUND: The prediction and prevention of influenza is a public health issue of great concern, and the study of timely acquisition of influenza transmission trend has become an important research topic. For achieving more quicker and accurate detection and prediction, the data recorded on the Internet, especially on the search engine from Google or Baidu are widely introduced into this field. Moreover, with the development of intelligent technology and machine learning algorithm, many updated and advanced trend tracking and forecasting methods are also being used in this research problem. METHODS: In this paper, a new recurrent neural network architecture, attention-based long short-term memory model is proposed for influenza surveillance. This is a kind of deep learning model which is trained by processing from Baidu Index series so as to fit the real influenza survey time series. Previous studies on influenza surveillance by Baidu Index mostly used traditional autoregressive moving average model or classical machine learning models such as logarithmic linear regression, support vector regression or multi-layer perception model to fit influenza like illness data, which less considered the deep learning structure. Meanwhile, some new model that considered the deep learning structure did not take into account the application of Baidu index data. This study considers introducing the recurrent neural network with long short-term memory combined with attention mechanism into the influenza surveillance research model, which not only fits the research problems well in model structure, but also provides research methods based on Baidu index. RESULTS: The actual survey data and Baidu Index data are used to train and test the proposed attention-based long short-term memory model and the other comparison models, so as to iterate the value of the model parameters, and to describe and predict the influenza epidemic situation. The experimental results show that our proposed model has better performance in the mean absolute error, mean absolute percentage error, index of agreement and other indicators than the other comparison models. CONCLUSION: Our proposed attention-based long short-term memory model vividly verifies the ability of this attention-based long short-term memory structure for better surveillance and prediction the trend of influenza. In comparison with some of the latest models and methods in this research field, the model we proposed is also excellent in effect, even more lightweight and robust. Future research direction can consider fusing multimodal data based on this model and developing more application scenarios.

Suppressing interface recombination in CZTSSe solar cells by simple selenization with synchronous interface gradient doping.

The main bottleneck in the development of kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells is their very low VOC due to severe carrier recombination. Specifically, due to the poor defect environment and unfavorable band structure, carrier recombination at the front interface is considered to be one of the most serious issues. Thus, to reduce the interface recombination and VOC deficit, we propose a convenient and effective strategy for Cd gradient doping near the front interface during selenization. The formed Cd gradient significantly reduced the CuZn defects and related [2CuZn + SnZn] defect clusters near the CZTSSe-CdS heterojunction, thus significantly suppressing the interface recombination near the heterojunction. Benefitting from the formed Cd gradient, a champion device with 12.14% PCE was achieved with the VOC significantly improved from 432 mV to 486 mV. The proposed element gradient doping strategy can offer a new idea for selenization and element gradient doping in other photoelectric devices.

Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Objectives: To identify a prognosis-related subtype of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) and comprehend its contributions to molecular characteristics, immune characteristics, and their potential benefits in immunotherapy and chemotherapy for HNSCC. Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis of CAFs from the samples of HNSCC patients derived from Gene Expression Omnibus (GEO), to identify the prognosis-related subtype of CAFs. CAFs were clustered into five subtypes, and a prognosis-related subtype was identified. Univariate and multivariate cox regression analyses were performed on the cohort selected from The Cancer Genome Atlas (TCGA) to determine signature construction, which was validated in GSE65858 and GSE42743. A prognostic signature based on 4 genes was constructed, which were derived from prognosis-related CAFs. The molecular characteristics, immune characteristics as well as the predicted chemosensitivity and immunotherapeutic response in the signature-defined subgroups were analyzed subsequently. Results: The patients with higher CAF scores correlated with poor survival outcomes. Additionally, a high CAF score correlated with lower infiltration levels of many immune cells including M1 macrophages, CD8+ T cells, follicular T helper cells, monocytes, and naïve B cells. High CAF score also demonstrated different enrichment pathways, mutation genes and copy number variated genes. Furthermore, patients with high CAF scores showed lower sensitivity for chemotherapy and immunotherapy than those with low CAF scores. Conclusion: The results of our study indicate the potential of the CAF signature as a biomarker for the prognosis of HNSCC patients. Furthermore, the signature could be a prospective therapeutic target in HNSCC.

Over 16% Efficient Solution-Processed Cu(In,Ga)Se2 Solar Cells via Incorporation of Copper-Rich Precursor Film.

Solution processing of Cu(In,Ga)Se2 (CIGS) absorber is a highly promising strategy for a cost-effective CIGS photovoltaic device. However, the device performance of solution-processed CIGS solar cells is still hindered by the severe non-radiative recombination resulting from deep defects and poor crystal quality. Here, a simple and effective precursor film engineering strategy is reported, where Cu-rich (CGI >1) CIGS layer is incorporated into the bottom of the CIGS precursor film. It has been discovered that the incorporation of the Cu-rich CIGS layer greatly improves the absorber crystallinity and reduces the trap state density. Accordingly, more efficient charge generation and charge transfer are realized. As a result of systematic processing optimization, the champion solution-processed CIGS device delivers an improved open-circuit voltage of 656 mV, current density of 33.15 mA cm-2 , and fill factor of 73.78%, leading to the high efficiency of 16.05%.

PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma.

Radiotherapy is a main treatment for esophageal squamous cell carcinoma (ESCC), but radioresistance leads to treatment failure ultimately. The combination of radiotherapy and PD-1 inhibitors showed significant antitumor effects. Our study showed that high-immune score, IFNG and CD8A level were associated with a low-radiosensitivity index (RSI) in the TCGA-ESCC cohort. And blocking PD-1 promoted exhausted T cells proliferation and IFN-γ expression. PD-1 inhibitor-reactivated T cells promoted G2/M-phase arrest, apoptosis and impaired DNA damage in radioresistant cells in an IFN-γ-dependent manner. Our study showed PD-1 inhibitors promote radiosensitivity though enhancing exhausted T cells expansion and IFN-γ expression, and highlights that neoadjuvant anti-PD-1 therapy and radiotherapy could offer an optimum strategy for improving cancer patients' outcome.

Plasmonic Local Electric Field-Enhanced Interface toward High-Efficiency Cu2ZnSn(S,Se)4 Thin-Film Solar Cells.

The kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells have shown a continuous rise in power conversion efficiencies in the past years. However, the encountered interfacial problems with respect to charge recombination and extraction losses at the CdS/CZTSSe heterojunction still hinder their further development. In this work, an additional plasmonic local electric field is imposed into the CdS/CZTSSe interface through the electrostatic assembly of a two-dimensional (2D) ordered Au@SiO2 NP array onto an aminosilane-modified surface absorber. The interfacial electric properties are tuned by controlling the coverage particle distance, and the finite-difference time domain (FDTD) simulation demonstrates that the strong near-field enhancement mainly occurs near the p-n junction interface. It is shown that the imposed local electric field leads to interfacial electrostatic potential (Velec) augmentation and improves the charge extraction and recombination processes. These electric benefits enable remarkable improvements in open-circuit voltage (Voc) and short-circuit current (Jsc), leading to the cell efficiency being increased from 10.19 to 11.50%. This work highlights the dramatic role of the plasmonic local electric field and the use of the 2D Au@SiO2 NP array to modify a surface absorber instead of the extensively used ion passivation, providing a new strategy for p-n junction engineering in kesterite photovoltaics.

Correlation of mismatch repair deficiency with clinicopathological features and programmed death-ligand 1 expression in thyroid carcinoma.

BACKGROUND: Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. METHODS: We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. RESULTS: In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p = 0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. CONCLUSIONS: MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

2-Keto-L-Gulonic Acid Improved the Salt Stress Resistance of Non-heading Chinese Cabbage by Increasing L-Ascorbic Acid Accumulation.

Salt stress has long been a prominent obstacle that restricts crop growth, and increasing the L-ascorbic acid (ASA) content of crops is an effective means of alleviating this stress. 2-Keto-L-gulonic acid (2KGA) is a precursor used in industrial ASA production as well as an ASA degradation product in plants. However, to date, no study has investigated the effects of 2KGA on ASA metabolism and salt stress. Here, we evaluated the potential of using 2KGA to improve crop resistance to salt stress (100mM NaCl) through a cultivation experiment of non-heading Chinese cabbage (Brassica campestris ssp. chinensis). The results showed that the leaf and root biomass were significantly improved by 2KGA application. The levels of metabolites and enzymes related to stress resistance were increased, whereas the hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents were decreased. Lipid peroxidation and cell membrane damage were alleviated following 2KGA treatment. Positive correlations were found between photosynthetic pigments and organic solutes, ASA and photosynthetic pigments, and ASA and antioxidant enzymes. In contrast, negative correlations were observed between antioxidant enzymes and H2O2/MDA. Moreover, the expression levels of L-gulono-1,4-lactone oxidase, GDP-mannose pyrophosphorylase, dehydroascorbate reductase-3, and ascorbate peroxidase were increased by 2KGA treatment. These results suggested that exogenous 2KGA application can relieve the inhibitory effect of salt stress on plant growth, and the promotion of ASA synthesis may represent a critical underlying mechanism. Our findings have significant implications for the future application of 2KGA or its fermentation residue in agriculture.

Comparative root transcriptome analysis of two soybean cultivars with different cadmium sensitivities reveals the underlying tolerance mechanisms.

Soybean can provide rich protein and fat and has great economic value worldwide. Cadmium (Cd) is a toxic heavy metal to organisms. It can accumulate in plants and be transmitted to the human body via the food chain. Cd is a serious threat to soybean development, particularly root growth. Some soybean cultivars present tolerant symptoms under Cd stress; however, the potential mechanisms are not fully understood. Here, we optimized RNA-seq to identify the differentially expressed genes (DEGs) in Cd-sensitive (KUAI) and Cd-tolerant (KAIYU) soybean roots and compared the DEGs between KAIYU and KUAI. A total of 1506 and 1870 DEGs were identified in the roots of KUAI and KAIYU, respectively. Through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene function analyses, we found that genes related to antioxidants and sequestration were responsible for Cd tolerance in KAIYU. In addition, overexpression of Glyma11g02661, which encodes a heavy metal-transporting ATPase, significantly improved Cd tolerance in transgenic hairy roots. These results provide a preliminary understanding of the tolerance mechanisms in response to Cd stress in soybean root development and are of great importance in developing Cd-resistant soybean cultivars by using the identified DEGs through genetic modification.

A 5'-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer.

BACKGROUND: tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. METHODS: Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. RESULTS: Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. CONCLUSIONS: Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.

Analysis of 25 Years of Polar Motion Derived from the DORIS Space Geodetic Technique Using FFT and SSA Methods.

Polar motion (PM) has a close relation to the Earth's structure and composition, seasonal changes of the atmosphere and oceans, storage of waters, etc. As one of the four major space geodetic techniques, doppler orbitography and radiopositioning integrated by satellite (DORIS) is a mature technique that can monitor PM through precise ground station positioning. There are few articles that have analyzed the PM series derived by the DORIS solution in detail. The aim of this research was to assess the PM time-series based on the DORIS solution, to better capture the time-series. In this paper, Fourier fast transform (FFT) and singular spectrum analysis (SSA) were applied to analyze the 25 years of PM time-series solved by DORIS observation from January 1993 to January 2018, then accurately separate the trend terms and periodic signals, and finally precisely reconstruct the main components. To evaluate the PM time-series derived from DORIS, they were compared with those obtained from EOP 14 C04 (IAU2000). The results showed that the RMSs of the differences in PM between them were 1.594 mas and 1.465 mas in the X and Y directions, respectively. Spectrum analysis using FFT showed that the period of annual wobble was 0.998 years and that of the Chandler wobble was 1.181 years. During the SSA process, after singular value decomposition (SVD), the time-series was reconstructed using the eigenvalues and corresponding eigenvectors, and the results indicated that the trend term, annual wobble, and Chandler wobble components were accurately decomposed and reconstructed, and the component reconstruction results had a precision of 3.858 and 2.387 mas in the X and Y directions, respectively. In addition, the tests also gave reasonable explanations of the phenomena of peaks of differences between the PM parameters derived from DORIS and EOP 14 C04, trend terms, the Chandler wobble, and other signals detected by the SSA and FFT. This research will help the assessment and explanation of PM time-series and will offer a good method for the prediction of pole shifts.

Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma.

Endeavors towards identifying key molecular markers for early diagnosis and treatment are driving the clinical study of papillary thyroid carcinoma (PTC). Recent studies have indicated that protein phosphatase, Mg2+/Mn2+ dependent, 1D (PPM1D) exerts an oncogenic function by increasing cell proliferation, migration and invasion in various cancer types. In addition, PPM1D has a high frequency of genetic alterations and has been proposed as a tumor driver in thyroid cancer, making PPM1D an attractive potential oncotarget for cancer treatment. The aims of the present study were to investigate the downstream targets of PPM1D and the potential molecular mechanisms of its oncogenic activities, as well as its clinical significance in PTC. As anticipated, PPM1D overexpression was confirmed in PTC clinical specimens. Furthermore, knockdown of PPM1D in thyroid cancer cell lines significantly suppressed the proliferation, migration and invasion but facilitated cell apoptosis. The protein levels of phosphorylated p38 mitogen­activated protein kinase (MAPK), p53 and Bax were increased in PPM1D­knockdown cells, while inhibition of p38 phosphorylation restored cell migration, proliferation and cell apoptosis. In addition, silencing of PPM1D expression induced nuclear translocation of p53 in K­1 and TPC­1 cells. The present results demonstrated that PPM1D regulated p38 MAPK and p53 signaling pathways to promote thyroid cancer progression. Collectively with the clinical results, these data qualified PPM1D as a potential diagnostic biomarker and therapeutic target in human thyroid cancer.

Germline Missense Mutation of Deleted in Malignant Brain Tumor 1 (DMBT1) in Familial Mediastinal Neuroendocrine Cancer and in vitro Effects in Thyroid Cancer Cells.

BACKGROUND: Neuroendocrine tumors (NETs) rarely occur in the mediastinum and their etiology and pathogenesis are still unclear. OBJECTIVES: This study assessed inherited or de novo mutations in familial mediastinal NETs. METHOD: DNA samples from 4 patients were subjected to the whole-exome sequencing, and Sanger sequencing was used to identify Deleted in malignant brain tumor 1 (DMBT1) mutations in all 45 family members. RESULTS: All patients showed a germline DMBT1 mutation at 4971C. Sanger sequencing data showed that 4 NETs and 2 carriers in the first patient's family and 2 NETs and 4 carriers in the second patient's family, respectively, had this DMBT1 mutation. The in vitro data showed that the ectopic expression of DMBT1 reduced tumor cell viability and migration by arresting the G1/S phase of the cell cycle. CONCLUSIONS: We identified a germline missense mutation in DMBT1D1657E as a susceptibility gene for familial mediastinal NETs.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients with Major Salivary Gland Mucoepidermoid Carcinoma.

Background: The aim of this study was to develop and validate prognostic nomograms predicting overall (OS) and cancer-specific survival (CSS) of patients with major salivary gland (MaSG) mucoepidermoid carcinoma (MEC). Methods: 1398 MaSG-MEC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. They were randomly and equally divided into a training cohort (n=699) and a validation cohort (n=699). The best subsets of covariates were identified to develop nomograms predicting OS and CSS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The nomograms were internally and externally validated by the bootstrap resampling method. The predictive ability was evaluated by Harrell's Concordance Index (C-index). Results: For the training cohort, eight (age at diagnosis, tumor grade, primary site, surgery, radiation, T, N and M classification) and seven predictors (all the above factors except primary site) were selected to create the nomograms estimating the 3- and 5- year OS and CSS, respectively. C-index indicated better predictive performance of the nomograms than the 7th AJCC staging system, which was confirmed by both internal (via the training cohort: OS: 0.888 vs 0.785, CSS: 0.938 vs 0.821) and external validation (via the validation cohort: OS: 0.844 vs 0.743, CSS: 0.882 vs 0.787). The calibration plots also revealed good agreements between the nomogram-based prediction and observed survival. Conclusions: We have proposed and validated the nomograms predicting OS and CSS of MaSG-MEC. They are proved to be of higher predictive value than the AJCC staging system and may be adopted in future clinical practice.

IL-17A increases MHC class I expression and promotes T cell activation in papillary thyroid cancer patients with coexistent Hashimoto's thyroiditis.

BACKGROUND: The incidence of coexisting papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) is increasing. The impact of HT on PTC prognosis and its possible mechanism remains controversial. Interleukin-17A (IL-17A) has been reported to participate in the pathogenesis of multiple autoimmune diseases and cancers. The aim of this study is to investigate the role of IL-17A in PTC with coexistent HT and evaluate the changes in tumor antigenicity. METHODS: Expression of IL-17A and major histocompatibility complex (MHC) class I molecules were compared on PTC tissue samples with or without HT. PTC cell lines K1 and TPC-1 were stimulated with IL-17A and analyzed for MHC class I expression afterwards. Cluster of differentiation (CD) 8+T cell activation, production of Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) as well as the programmed death-1 (PD-1) expression on lymphocytes were assessed by coculture of donor peripheral blood lymphocytes (PBLs) with IL-17A pretreated PTC cells. RESULTS: Elevated IL-17A and MHC class I expression were observed in PTC tissue samples with coexistent HT. Stimulation of PTC cells with IL-17A effectively increased MHC class I expression in vitro. Coculture of PBLs with IL-17A pretreated PTC cells resulted in enhanced T cell activation (%CD25+ of CD3+T cells) and increased IL-2 production along with decreased IFN-γ secretion and PD-1 expression of the lymphocytes. CONCLUSIONS: Papillary thyroid cancer with coexisting Hashimoto's thyroiditis presents elevated MHC class I expression, which may be the result of IL-17A secretion. T cell activation is enhanced in vitro by IL-17A and may provide future utility in PTC immunotherapy.