The aim of this study was to investigate the prognostic value of tumor markers in operable non-small cell lung cancer (NSCLC) patients. A total of 481 NSCLC patients were enrolled in the present ...study. High levels of neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) were detected in 306 (63.6%), 89 (18.5%) and 125 (26.0%) patients, respectively. Seventy-eight of 481 patients died of disease progression, and the median disease-free survival (DFS) and overall survival (OS) were 16.0 and 21.0 months, respectively. The three-year DFS rate was 56.7%, and the OS rate was 75.3%. For serum NSE, the three-year cumulative DFS rate for the normal and elevated group was 67.7% and 51.8% (p = 0.007). The OS in patients with high and normal levels of NSE was 34.0 months and 48.0 months, respectively. The median DFS was 46.0 months versus 32.0 months (p = 0.001), and the OS was 48.0 months versus 44.0 months (p = 0.001) in patients with normal and high levels of CA125. For patients with squamous cell carcinoma, the overall survival was significantly shorter in patients with elevated levels of SCC (p = 0.041). In the multivariate analysis high levels of NSE, CA125 and clinical stage were significantly correlated with worse prognosis (p < 0.05). Patients with all three tumor markers elevated presented the worst prognosis (p < 0.05). In our analysis, high levels of preoperative serum NSE and CA125 are correlated with worse survival in operable NSCLC patients.
Sun-induced chlorophyll fluorescence (SIF) has shown potential in quantifying plant responses to environmental changes by which abiotic drivers are dominated. However, SIF is a mixed signal ...influenced by factors such as leaf physiology, canopy structure, and sun-sensor geometry. Whether the physiological information contained in SIF can better quantify crop disease stresses dominated by biological drivers, and clearly explain the physiological variability of stressed crops, has not yet been sufficiently explored. On this basis, we took winter wheat naturally infected with stripe rust as the research object and conducted a study on the responses of physiological signals and reflectivity spectrum signals to crop disease stress dominated by biological drivers, based on in situ canopy-scale and leaf-scale data. Physiological signals include SIF, SIFyield (normalized by absorbed photosynthetically active radiation), fluorescence yield (ΦF) retrieved by NIRvP (non-physiological components of canopy SIF) and relative fluorescence yield (ΦF-r) retrieved by near-infrared radiance of vegetation (NIRvR). Reflectance spectrum signals include normalized difference vegetation index (NDVI) and near-infrared reflectance of vegetation (NIRv). At the canopy scale, six signals reached extremely significant correlations (P < 0.001) with disease severity levels (SL) under comprehensive experimental conditions (SL without dividing the experimental samples) and light disease conditions (SL < 20%). The strongest correlation between NDVI and SL (R = 0.69) was observed under the comprehensive experimental conditions, followed by NIRv (R = 0.56), ΦF-r (R = 0.53) and SIF (R = 0.51), and the response of ΦF (R = 0.45) and SIFyield (R = 0.34) to SL was weak. Under lightly diseased conditions, ΦF-r (R = 0.62) showed the strongest response to disease, followed by SIFyield (R = 0.60), SIF (R = 0.56) and NIRv (R = 0.54). The weakest correlation was observed between ΦF and SL (R = 0.51), which also showed a result approximating NDVI (R = 0.52). In the case of a high level of crop disease severity, NDVI showed advantages in disease monitoring. In the early stage of crop diseases, which we pay more attention to, compared with SIF and reflectivity spectrum signals, ΦF-r estimated by the newly proposed ‘NIRvR approach’ (which uses SIF together with NIRvR (i.e., SIF/ NIRvR) as a substitute for ΦF) showed superior ability to monitor crop physiological stress, and was more sensitive to plant physiological variation. At the leaf scale, the response of SIF to SL was stronger than that of NDVI. These results validate the potential of ΦF-r estimated by the NIRvR approach to monitoring disease stress dominated by biological drivers, thus providing a new research avenue for quantifying crop responses to disease stress.
Solar-induced chlorophyll fluorescence (SIF) has great advantages in the remote sensing detection of crop stress. However, under stripe rust stress, the effects of canopy structure and leaf ...physiology on the variations in canopy SIF are unclear, and these influencing factors are entangled during the development of disease, resulting in an unclear coupling relationship between SIFcanopy and the severity level (SL) of disease, which affects the remote sensing detection accuracy of wheat stripe rust. In this study, the observed canopy SIF was decomposed into NIRVP, which can characterize the canopy structure, and SIFtot, which can sensitively reflect the physiological status of crops. Additionally, the main factors driving the variations in canopy SIF under different disease severities were analyzed, and the response characteristics of SIFcanopy, NIRVP, and SIFtot to SL under stripe rust stress were studied. The results showed that when the severity level (SL) of disease was lower than 20%, NIRVP was more sensitive to variation in SIFcanopy than SIFtot, and the correlation between SIFtot and SL was 6.6% higher than that of SIFcanopy. Using the decomposed SIFtot component allows one to detect the stress state of plants before variations in vegetation canopy structure and leaf area index and can realize the early diagnosis of crop diseases. When the severity level (SL) of disease was in the state of moderate incidence (20% < SL ≤ 45%), the variation in SIFcanopy was affected by both NIRVP and SIFtot, and the detection accuracy of SIFcanopy for wheat stripe rust was better than that of the NIRVP and SIFtot components. When the severity level (SL) of disease reached a severe level (SL > 45%), SIFtot was more sensitive to the variation in SIFcanopy, and NIRVP reached a highly significant level with SL, which could better realize the remote sensing detection of wheat stripe rust disease severity. The research results showed that analyzing variations in SIFcanopy by using the decomposed canopy structure and physiological response signals can effectively capture additional information about plant physiology, detect crop pathological variations caused by disease stress earlier and more accurately, and promote crop disease monitoring and research progress.
Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic ...leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1
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seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
The wheat canopy reflectance spectrum is affected by many internal and external factors such as diseases and growth stage. Separating the effects of disease stress on the crop from the observed mixed ...signals is crucial for increasing the precision of remote sensing monitoring of wheat stripe rust. The canopy spectrum of winter wheat infected by stripe rust was processed with the difference-in-differences (DID) algorithm used in econometrics. The monitoring accuracies of wheat stripe rust before and after processing with the DID algorithm were compared in the presence of various external factors, disease severity, and several simulated satellite sensors. The correlation between the normalized difference vegetation index processed by the DID algorithm (NDVI-DID) and the disease severity level (SL) increased in comparison with the NDVI before processing. The increase in precision in the natural disease area in the field in the presence of large differences in growth stage, growth, planting, and management of the crop was greater than that in the controlled experiment. For low disease levels (SL < 20%), the R2 of the regression of NDVI-DID on SL was 38.8% higher than that of the NDVI and the root mean square error (RMSE) was reduced by 11.1%. The increase in precision was greater than that for the severe level (SL > 40%). According to the measured hyperspectral data, the spectral reflectance of three satellite sensor levels was simulated. The wide-band NDVI was calculated. Compared with the wide-band NDVI and vegetation indexes (VIS) before DID processing, there were increases in the correlation between SL and the various types of VIS-DID, as well as in the correlation between SL and NDVI-DID. It is feasible to apply the DID algorithm to multispectral satellite data and diverse types of VIS for monitoring wheat stripe rust. Our results improve the quantification of independent effects of stripe rust infection on canopy reflectance spectrum, increase the precision of remote sensing monitoring of wheat stripe rust, and provide a reference for remote sensing monitoring of other crop diseases.
Cullin-RING E3 ligases （CRLs） regulate different aspects of plant development and are activated by modification of their cullin subunit with the ubiquitin-like protein NEDD8 （NEural precursor cell ...expressed Developmentally Down-regulated 8） （neddylation） and deactivated by NEDD8 removal （deneddylation）. The CONSTITUTIVELY PHOTOMORPHOGENIC9 （COP9） signalosome （CSN） acts as a molecular switch of CRLs activity by reverting their neddylation status, but its contribution to embryonic and early seedling development remains poorly characterized. Here, we analyzed the phenotypic defects of csn mutants and monitored the cullin deneddylation/neddylation ratio during embryonic and early seedling development. We show that while csn mutants can complete embryogenesis （albeit at a slower pace than wildtype） and are able to germinate （albeit at a reduced rate）, they progressively lose meristem activity upon germination until they become unable to sustain growth. We also show that the majority of cullin proteins are progressively neddylated during the late stages of seed maturation and become deneddylated upon seed germination. This developmentally regulated shift in the cullin neddylation status is absent in csn mutants. We conclude that the CSN and its cullin deneddylation activity are required to sustain postembryonic meristem function in Arabidopsis.
Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that ...of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.
Solar-induced chlorophyll fluorescence (SIF) shows potential in exploring plant responses to environmental changes caused by extreme climatic factors. However, how to accurately assess climate ...stresses (especially the low-temperature stress) suffered on crops at the regional scale in a systematic approach has not been extensively explored. In this study, we developed a climate vegetation stress index (CVSI) to assess and quantify the impacts of climate stress on crops at large scales by combining TROPOspheric Monitoring Instrument (TROPOMI) SIF and land surface temperature (LST) data through an easy-to-operate approach. This index was employed to identify low-temperature stress conditions in Henan Province’s winter wheat in 2018. Results indicate that, influenced by climate characteristics, crops in the northern part of Henan Province experienced more severe low-temperature stress than those in the southern part. The daily average SIF values experienced reductions of 0.74, 0.45, 0.61, and 0.86 mW Formula Omitted srFormula Omitted nm−1 during the four cooling episodes within the two phenological periods, respectively. As low-temperature stress intensified, winter wheat growth was hindered, reducing grain yield. Indeed, the CVSI provides an accurate depiction of crop stress levels and patterns. In areas with high-CVSI values, yield losses are particularly severe. In addition, the significant positive correlation between the CVSI and net primary productivity (NPP), along with the similar spatial intensity pattern, shows the effectiveness of CVSI in monitoring low-temperature stress. CVSI provides a new approach to understand the impacts of climate change on overwintering crops and offers a practical reference for climate stress effects monitoring at the regional scale.
BACKGROUND RET rearrangements have been reported in 30% of papillary thyroid carcinomas and 1-2% of non-small cell lung cancer (NSCLC). In these tumors, RET gene fusion product provides a ...constitutively active tyrosine kinase (TKR), leading to uncontrolled cellular proliferation, differentiation, and migration. In this investigation we assessed the positivity rate of RET gene rearrangement in primary and metastatic non-small cell lung cancer and explored their relationships. MATERIAL AND METHODS Between January 2013 and May 2015, we collected 384 cases of primary metastatic non-small cell lung cancer, which included 246 matched metastatic tumors cases from multiple centers. The RET rearrangement uniformity in metastatic lymph nodes and tumor specimens were contrasted and the relationships between RET rearrangement and patients' clinical features were investigated. RESULTS For those 384 cases, 7 (1.82%) cases had tumors with identified RET rearrangement. Among the 246 paired cases, 3 (1.22%) cases of primary tumor had identified RET rearrangement and 2 (0.81%) cases of metastases had identified RET rearrangement. The sensitivity was 66.67% (2/3) and the specificity was 100% (243/243). CONCLUSIONS The results of this research indicate that the metastases of non-small cell lung cancer can predict RET rearrangement of the primary tumor tissue in the majority of cases. Testing for RET rearrangement in metastases can be used as an alternative to testing of primary tumor tissue if it is inaccessible.
Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and ...progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis.
•hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer.•The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines.•hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.
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