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1.
Small ; 20(9): e2304866, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37863810

RESUMO

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.

2.
Small ; 18(39): e2203443, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36026573

RESUMO

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%.

3.
Genome ; : 1-16, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648728

RESUMO

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.

4.
Neuroendocrinology ; 110(7-8): 714-720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31655821

RESUMO

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.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação a DNA/genética , Neoplasias do Mediastino/genética , Tumores Neuroendócrinos/genética , Neoplasias da Glândula Tireoide/patologia , Proteínas Supressoras de Tumor/genética , Ciclo Celular/genética , Família , Feminino , Técnicas de Transferência de Genes , Mutação em Linhagem Germinativa , Humanos , Masculino , Neoplasias do Mediastino/patologia , Mutação de Sentido Incorreto , Tumores Neuroendócrinos/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/fisiopatologia , Células Tumorais Cultivadas
5.
Sensors (Basel) ; 20(10)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429329

RESUMO

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.

6.
Sensors (Basel) ; 19(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141928

RESUMO

For existing wireless network devices and smart phones to achieve available positioning accuracy easily, fingerprint localization is widely used in indoor positioning, which depends on the differences of the Received Signal Strength Indicator (RSSI) from the Wireless Local Area Network (WLAN) in different places. Currently, most researchers pay more attention to the improvement of online positioning algorithms using RSSI values, while few focus on the MAC (media access control) addresses received from the WLAN. Accordingly, we attempt to integrate MAC addresses and RSSI values simultaneously in order to realize indoor localization within multi-story buildings. A novel approach to indoor positioning within multi-story buildings is presented in this article, which includes two steps: firstly, to identify the floor using the difference of received MAC addresses in different floors; secondly, to implement further localization on the same floor. Meanwhile, clustering operation using MAC addresses as the clustering index is introduced in the online positioning phase to improve the efficiency and accuracy of indoor positioning. Experimental results show that the proposed approach can achieve not only the precise location with the horizontal accuracy of 1.8 meters, but also the floor where the receiver is located within multi-story buildings.

7.
Small Methods ; : e2400041, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38766987

RESUMO

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.

8.
Adv Sci (Weinh) ; 11(35): e2405016, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39031982

RESUMO

It has been validated that enhancing crystallinity and passivating the deep-level defect are critical for improving the device performance of kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Coordination chemistry interactions within the Cu-Zn-Sn-S precursor solution play a crucial role in the management of structural defects and the crystallization kinetics of CZTSSe thin films. Therefore, regulating the coordination environment of anion and cation in the precursor solution to control the formation process of precursor films is a major challenge at present. Herein, a synergetic crystallization modulation and defect passivation method is developed using P2S5 as an additive in the CZTS precursor solution to optimize the coordination structure and improve the crystallization process. The alignment of theoretical assessments with experimental observations confirms the ability of the P2S5 molecule to coordinate with the metal cation sites of CZTS precursor films, especially more liable to the Zn2+, effectively passivating the Zn-related defects, thereby significantly reducing the defect density in CZTSSe absorbers. As a result, the device with a power conversion efficiency of 14.36% has been achieved. This work provides an unprecedented strategy for fabricating high-quality thin films by anion-coordinate regulation and a novel route for realizing efficient CZTSSe solar cells.

9.
Biotechnol Lett ; 35(11): 1853-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23881329

RESUMO

A novel two-helper-strain co-culture system (TSCS) was developed to enhance 2-keto-L-gulonic acid (2-KLG) productivity for vitamin C production. Bacillus megaterium and B. cereus (with a seeding culture ratio of 1:3, v/v), used as helper strains, increased the 2-KLG yield using Ketogulonigenium vulgare compared to the conventional one-helper-strain (either B. cereus or B. megaterium) co-culture system (OSCS). After 45 h cultivation, 2-KLG concentration in the TSCS (69 g l(-1)) increased by 8.9 and 7 % over that of the OSCS (B. cereus: 63.4 g l(-1); B. megaterium: 64.5 g l(-1)). The fermentation period of TSCS was 4 h shorter than that of OSCS (B. cereus). The increased cell numbers of K. vulgare stimulated by the two helper strains possibly explain the enhanced 2-KLG yield. The results imply that TSCS is a viable method for enhancing industrial production of 2-KLG.


Assuntos
Bacillus cereus/crescimento & desenvolvimento , Bacillus megaterium/crescimento & desenvolvimento , Rhodobacteraceae/crescimento & desenvolvimento , Rhodobacteraceae/metabolismo , Açúcares Ácidos/metabolismo , Fermentação , Fatores de Tempo
10.
PLoS One ; 18(1): e0280834, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36689543

RESUMO

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.


Assuntos
Influenza Humana , Humanos , Influenza Humana/epidemiologia , Memória de Curto Prazo , Modelos Teóricos , Modelos Lineares , Redes Neurais de Computação , Previsões
11.
Endocrinology ; 164(4)2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36726346

RESUMO

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.


Assuntos
RNA Longo não Codificante , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/patologia , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , China , Neoplasias da Glândula Tireoide/genética
12.
Nanoscale ; 15(20): 8900-8924, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37129945

RESUMO

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.

13.
ACS Appl Mater Interfaces ; 15(48): 55652-55658, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37991928

RESUMO

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.

14.
Front Genet ; 13: 1028469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568368

RESUMO

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.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35653219

RESUMO

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.

16.
Radiat Res ; 198(5): 458-466, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35993821

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/radioterapia , Inibidores de Checkpoint Imunológico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Linfócitos T/metabolismo , Tolerância a Radiação , Proliferação de Células , Apoptose , Mitose
17.
Nanoscale ; 15(1): 185-194, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36475511

RESUMO

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.

18.
Endocrine ; 76(3): 660-670, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35366156

RESUMO

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.


Assuntos
Antígeno B7-H1 , Neoplasias da Glândula Tireoide , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/genética
19.
J Exp Clin Cancer Res ; 40(1): 222, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225773

RESUMO

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.


Assuntos
Fatores de Processamento de RNA/metabolismo , RNA de Transferência de Glicina/metabolismo , RNA de Transferência/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Processamento Alternativo , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fatores de Processamento de RNA/genética , RNA de Transferência/genética , RNA de Transferência de Glicina/genética , Transdução de Sinais , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
20.
Front Plant Sci ; 12: 697184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804078

RESUMO

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.

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