Investigation on the interaction of NH3&CH4 co-activated char under reburning conditions.

In the current global context, there is a pressing need to curtail greenhouse gas emissions, making the utilization of a coal and zero-carbon energy blend an imperative strategy for reducing carbon emissions from coal-fired power generation. The planar flame burner serves as a tool to simulate the temperature and atmospheric conditions within the reburning zone, facilitating extensive examination of the physical and chemical structural alterations, as well as the nitrogen oxide reduction potential, during NH3/CH4 activation for reburning pulverized coal. Experimental results underscore that blending high-activity fuels optimizes the combustion performance of coal char. Through the addition of NH3 and CH4, the NO reduction capability of coal char is bolstered by approximately 0.67 times compared to sole reliance on recirculating flue gas transport. Furthermore, NH3 introduction facilitates the conversion of C]O double bonds into C-O single bonds, rendering them more amenable to reduction by NO. While the joint influence of NH3 and CH4 does not significantly impact char particle size, it does foster the evolution of N-Q to N-5 and N-6 on the char surface. Furthermore, there was a significant increase in the BET-specific surface area, which rose by 50%. Additionally, the total pore volume increased by approximately 21.43%. The comprehensive understanding of NH3 and CH4 modified pulverized coal reburning technology holds significant promise for optimizing power plant operations and mitigating carbon dioxide and nitrogen oxide emissions.

Automated highway pavement crack recognition under complex environment.

The pavement is vulnerable to damage from natural disasters, accidents and other human factors, resulting in the formation of cracks. Periodic pavement monitoring can facilitate prompt detection and repair the pavement diseases, thereby minimizing casualties and property losses. Due to the presence of numerous interferences, recognizing highway pavement cracks in complex environments poses a significant challenge. Nevertheless, several computer vision approaches have demonstrated notable success in tackling this issue. We have employed a novel approach for crack recognition utilizing the ResNet34 model with a convolutional block attention module (CBAM), which not only saves parameters and computing power but also ensures seamless integration of the module as a plug-in. Initially, ResNet18, ResNet34, and ResNet50 models were trained by employing transfer learning techniques, with the ResNet34 network being selected as a fundamental model. Subsequently, CBAM was integrated into ResBlock and further training was conducted. Finally, we calculated the precision, average recall on the test set, and the recall of each class. The results demonstrate that by integrating CBAM into the ResNet34 network, the model exhibited improved test accuracy and average recall compared to its previous state. Moreover, our proposed model outperformed all other models in terms of performance. The recall rates for transverse crack, longitudinal crack, map crack, repairing, and pavement marking were 88.8%, 86.8%, 88.5%, 98.3%, and 99.9%, respectively. Our model achieves the highest precision of 92.9% and the highest average recall of 92.5%. However, the effectiveness in detecting mesh cracks was found to be unsatisfactory, despite their significant prevalence. In summary, the proposed model exhibits great potential for crack identification and serves as a crucial foundation for highway maintenance.

Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?

Biomaterials, when implanted in the human body, can induce a series of cell- and cytokine-related reactions termed foreign body reactions (FBRs). In the progression of FBRs, macrophages regulate inflammation and healing by polarizing to either a pro-inflammatory or pro-healing phenotype and recruit fibroblasts by secreting cytokines. Stimulated by the biomaterials, fibrotic capsule is formed eventually. The implant, along with its newly formed capsule, introduces various mechanical cues that influence cellular functions. Mechanosensing proteins, such as integrins or ion channels, transduce extracellular mechanical signals into cytoplasm biochemical signals in response to mechanical stimuli. Consequently, the morphology, migration mode, function, and polarization state of the cells are affected. Modulated by different intracellular signaling pathways and their crosstalk, the expression of fibrotic genes increases with fibroblast activation and fibroblast to myofibroblast transition under stiff or force stimuli. However, summarized in most current studies, the outcomes of macrophage polarization in the effect of different mechanical cues are inconsistent. The underlying mechanisms should be investigated with more advanced technology and considering more interfering aspects. Further research is needed to determine how to modulate the progression of fibrotic capsule formation in FBR artificially.

Integrated proteomic and metabolomic analysis of plasma reveals regulatory pathways and key elements in thyroid cancer.

Thyroid cancer (TC) is the most common endocrine malignancy with increasing incidence in recent years. Fine-needle aspiration biopsy (FNAB), as a gold standard for the initial evaluation of thyroid nodules, fails to cover all the cytopathologic conditions resulting in overdiagnosis. There is an urgent need for a better classification of thyroid cancer from benign thyroid nodules (BTNs). Here, data independent acquisition (DIA)-based proteomics and untargeted metabolomics in plasma samples of 10 patients with TC and 15 patients with BTNs were performed. Key proteins and metabolites were identified specific to TC, and an independent cohort was used to validate the potential biomarkers using enzyme-linked immunosorbent assay (ELISA). In total, 1429 proteins and 1172 metabolites were identified. Principal component analysis showed a strong overlap at the proteomic level and a significant discrimination at the metabolomic level between the two groups, indicating a more drastic disturbance in the metabolome of thyroid cancer. Integrated analysis of proteomics and metabolomics shows glycerophospholipid metabolism and arachidonic acid metabolism as key regulatory pathways. Furthermore, a multi-omics biomarker panel was developed consisting of LCAT, GPX3 and leukotriene B4. Based on the AUC value for the discovery set, the classification performance was 0.960. The AUC value of the external validation set was 0.930. Altogether, our results will contribute to the clinical application of potential biomarkers in the diagnosis of thyroid cancer.

Effect of isorhamnetin on carbonic anhydrase IX expression and tumorigenesis of bladder cancer by activating PPARγ/PTEN/AKT pathway.

BACKGROUND: To clarify the research prospect and mechanism analysis of isorhamnetin as a therapeutic drug for bladder cancer. METHODS: Firstly, the effects of different concentrations of isorhamnetin on the expression of PPARγ/PTEN/Akt pathway protein, CA9, PPARγ, PTEN and AKT protein were discussed by western blot. The effects of isorhamnetin on the growth of bladder cells were also analyzed. Secondly, we verified whether the effect of isorhamnetin on CA9 was related to PPARγ/PTEN/Akt pathway by western blot, and the mechanism of isorhamnetin on the growth of bladder cells is related to this pathway by CCK8, cell cycle and ball formation experiment. Further, nude mouse model of subcutaneous tumor transplantation was constructed to analyze the effects of isorhamnetin, PPAR and PTEN on 5637 cell tumorigenesis and the effects of isorhamnetin on tumorigenesis and CA9 expression through PPARγ/PTEN/Akt pathway. RESULTS: Isorhamnetin inhibited the development of bladder cancer, and regulated the expression of PPAR, PTEN, AKT, CA9. Isorhamnetin inhibits cell proliferation and the transition of cells from G0/G1 phase to S phase, and tumor sphere formation. Carbonic anhydrase IX is a potential downstream molecule of PPARγ/PTEN/AKT pathway. Overexpression of PPARγ and PTEN inhibited expression of CA9 in bladder cancer cells and tumor tissues. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity. CONCLUSION: Isorhamnetin has the potential to become a therapeutic drug for bladder cancer, whose antitumor mechanism is related to PPARγ/PTEN/AKT pathway. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity.

Research on NO generation characteristics of ammonia-premixed flame.

Ammonia is a promising fuel with high energy density, accessible storage, and no CO2 production by combustion, but its combustion produces the pollutant NO. In this study, a Bunsen burner experimental bench was selected to investigate the concentration of NO generated by ammonia combustion at different initial oxygen concentrations. Further, the reaction pathways of NO were analyzed in depth, and sensitivity analysis was performed. The results show that the Konnov mechanism has an excellent predictive effect on NO generated by ammonia combustion. In the ammonia-premixed laminar flame at atmospheric pressure, the NO concentration peaked at an equivalence ratio of 0.9. The high initial oxygen concentration enhanced the combustion of ammonia-premixed flame and increased the conversion of NH3 to NO. NO was not only a product but a contribution to the combustion of NH3. As the equivalence ratio increases, NH2 consumes a large amount of NO and reduces NO production. The high initial oxygen concentration enhanced NO production, and the effect was more pronounced at low equivalents. The study results provide theoretical guidance for the utilization of ammonia combustion and pollutant reduction and help to drive the process of ammonia combustion toward practicality.

Numerical simulation on the deposition characteristics of MSWI fly ash particles in a cyclone furnace.

In melting municipal solid waste incineration (MSWI) fly ash by cyclone furnace, the deposition characteristics of particles affect the slag flow and the secondary MSWI fly ash formation. In this study, the composition mechanism based on critical viscosity is selected as the particle deposition model to predict the deposition and rebound of particles on the furnace wall. The Riboud model with an accurate viscosity prediction performance is selected, then the particle deposition model is integrated into a commercial computational fluid dynamics (CFD) solver through the user-defined function (UDF) to realize the coupling of particle motion and deposition process. The results show that under the same case, the deposition rate decreases obviously with the increase of MSWI fly ash particle size. And the escape rate reaches a maximum at particle size 120 µm. Controlling the particle size of fly ash particles within 60 µm can effectively reduce the generation of secondary MSWI fly ash. During the forward movement of the fly ash inlet position, the escape of MSWI fly ash particles with large particle sizes has been significantly weakened. This measure not only lowers the post-treatment cost but also dramatically reduces the pretreatment step of MSWI fly ash before the melting and solidification process. In addition, the deposition rate and quality will reach the maximum values, respectively, along with gradually increasing MSWI fly ash input flow. Overall, this study has the guiding significance for reducing the pretreatment steps and post-treatment costs of MSWI fly ash by melting in the cyclone furnace.

Case report: Lymph node metastases of breast cancer and thyroid cancer encountered in axilla.

Occurrences of breast cancer and thyroid cancer metachronously or synchronously are common for women, but axillary lymph node metastasis from both cancers is rarely seen. We report a patient who had two metastatic lymph nodes from papillary thyroid carcinoma after axillary lymph node dissection with mastectomy. Papillary thyroid carcinoma diagnosis was ensured after thyroidectomy. A literature review revealed that even the co-occurrence of breast cancer and thyroid cancer is not rare, but the etiology behind this phenomenon is not elucidated well. Genetic disorders, thyroid dysfunction, and hormone receptors may be relevant. Considering the rareness of axillary lymph node metastasis of thyroid cancer, adjuvant therapy and surgery treatment for this kind of case should be considered elaborately.

Reburning pulverized coal with natural gas/syngas upgrading: NO reducing ability and physicochemical structure evolution of coal char.

The lifting gas activates the coal particles, which increases their ability to reduce NO. This technique overcomes the oxygen consumption of large pulverized coal in the early stages of re-firing during air/flue gas transport of pulverized coal. This study conducted experiments on a planar flame burner bench to analyze the physicochemical structure evolution of coal coke after natural gas and syngas activation using FTIR, XPS, and BET. The NO reduction capacity was tested on a micro fluidized bed reaction test bench. The results show that natural gas's upgrading effect is better than syngas. Hydrogen and hydrocarbon radicals generated by the reaction of natural gas with oxygen play a significant role in activation. After upgrading by natural gas, the specific surface area of carbon increased by about 54.2 %, the total pore volume increased by about 51.2 %, the whole oxygen-containing groups decreased by nearly 4.4 %, the total amount of alkyl complexes increased by about 3.6 %, and the nitric oxide reducing ability increased by almost 75 %. The technology minimizes expensive reactive gases while ensuring less reburned coal is used to reduce NOx emissions.

Clinical outcomes of multifocal papillary thyroid cancer: A systematic review and meta-analysis.

Objective: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a steadily increasing incidence. Researches have reported that tumor multifocality occurs in an extensive number of cases. Nevertheless, the clinical characteristics and prognostic value remained controversial. This study was performed to investigate the relationship between multifocal PTC and adverse clinicopathologic features and the prognosis. Methods: A systematic review and meta-analysis were conducted based on three electronic databases up to December 31, 2021. Parameters of interest included five clinical features (extrathyroidal extension, lymphovascular invasion, central lymph node metastasis, lateral lymph node metastasis, distant metastasis) and were pooled into risk ratios (RRs). Time-to-event data (recurrence-free survival and all-cause mortality) were evaluated using hazard ratios (HRs). Publication bias was examined using funnel plots and Egger's test. Results: A total of 23 articles were included according to the inclusion criteria; all of the studies were retrospective cohorts. In comparison with unifocality, multifocality showed an increased risk of extrathyroidal extension (RR 1.38, 95% CI 1.25-1.53), lymphovascular invasion (RR 1.27, 95% CI 1.04-1.55), central lymph node metastasis (RR 1.21, 95% CI 1.12-1.30), lateral lymph node metastasis (RR 1.86, 95% CI 1.62-2.14), and distant metastasis (RR 1.35, 95% CI 1.03-1.76). Multifocal patients were predisposed to postoperative recurrence (HR 1.76, 95% CI 1.50-2.07). The rate of all-cause mortality did not reach a statistical difference. Level of Evidence: 2. Conclusion: Multifocal PTC is more aggressive in contrast to unifocal PTC and is accompanied by an increased risk of recurrence. They were usually diagnosed in higher grades and stages. To achieve the maximal benefit, we recommend personalized therapy and close follow-up for multifocal PTC patients. Further prospective studies will clarify the best-fitted treatment plans.

Clonal Distribution and Intratumor Heterogeneity of the TCR Repertoire in Papillary Thyroid Cancer With or Without Coexistent Hashimoto's Thyroiditis.

The intratumor heterogeneity (ITH) of the amount and TCR repertoires of tumor infiltrating lymphocytes (TILs) in PTC with and without coexistent Hashimoto's thyroiditis (HT) are unclear. Here, we investigated the amount of T cells in tumor and corresponding normal tissues by immunohistochemical staining on 80 tumor samples and 40 normal samples from 40 patients. The immune repertoire of T cells was identified on 24 tumor samples and 12 normal samples from 12 patients using TCR high-throughput sequencing. The results demonstrated that the numbers of CD3+, CD4+ and CD8+ T cells in PTC without coexistent HT (PTC-WO) were significantly lower than those in PTC with existing HT (PTC-W). In PTC-W, the density of CD4+ TILs were generally higher when compared with CD8+ TILs. Furthermore, we found that the numbers of CD3+ T cells and their CD4+, CD8+ subtypes in tumor samples were generally higher than those in normal tissue in PTC-WO and moreover, the number of CD3+ T cells was negatively associated with TCR clonality in PTC-WO. In addition, although ITH of the TCR repertoire truly existed in PTC-W and PTC-WO, the TCR repertoires between distinct regions of the non-adjacent tumor foci were presented with a higher degree of similarity than those between tumor and matched normal tissue in PTC-WO, yet the similarity of intratumor repertoires was not significantly higher than those between tumor and corresponding normal samples in PTC-W. This research comprehensively delineated the quantity and TCR repertoire ITH of T cells in PTC-W and PTC-WO, suggesting that TILs might be reactive to tumor antigens in PTC-WO. Moreover, multiregion biopsies should be performed to precisely identify the immune background in PTC-W and PTC-WO.

Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance.

Trastuzumab, a targeted anti-human epidermal-growth-factor receptor-2 (HER2) monoclonal antibody, represents a mainstay in the treatment of HER2-positive (HER2+) breast cancer. Although trastuzumab treatment is highly efficacious for early-stage HER2+ breast cancer, the majority of advanced-stage HER2+ breast cancer patients who initially respond to trastuzumab acquire resistance to treatment and relapse, despite persistence of HER2 gene amplification/overexpression. Here, we sought to leverage HER2 overexpression to engage antibody-dependent cellular phagocytosis (ADCP) through a combination of trastuzumab and anti-CD47 macrophage checkpoint immunotherapy. We have previously shown that blockade of CD47, a surface protein expressed by many malignancies (including HER2+ breast cancer), is an effective anticancer therapy. CD47 functions as a "don't eat me" signal through its interaction with signal regulatory protein-α (SIRPα) on macrophages to inhibit phagocytosis. Hu5F9-G4 (magrolimab), a humanized monoclonal antibody against CD47, blocks CD47's "don't eat me" signal, thereby facilitating macrophage-mediated phagocytosis. Preclinical studies have shown that combining Hu5F9-G4 with tumor-targeting antibodies, such as rituximab, further enhances Hu5F9-G4's anticancer effects via ADCP. Clinical trials have additionally demonstrated that Hu5F9-G4, in combination with rituximab, produced objective responses in patients whose diffuse large B cell lymphomas had developed resistance to rituximab and chemotherapy. These studies led us to hypothesize that combining Hu5F9-G4 with trastuzumab would produce an anticancer effect in antibody-dependent cellular cytotoxicity (ADCC)-tolerant HER2+ breast cancer. This combination significantly suppressed the growth of ADCC-tolerant HER2+ breast cancers via Fc-dependent ADCP. Our study demonstrates that combining trastuzumab and Hu5F9-G4 represents a potential new treatment option for HER2+ breast cancer patients, even for patients whose tumors have progressed after trastuzumab.

LINC00958 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of oesophageal squamous cell carcinoma cells.

Oesophageal cancer is one of the deadliest cancers in the world. Oesophageal squamous cell carcinoma (ESCC) is the most prevalent histological type of oesophageal cancer. Oesophageal cancer has a poor prognosis because of its invasiveness. Thus, it is especially important to seek effective treatment methods. Research indicates that long non-coding RNAs (lncRNAs) play a significant role in the occurrence and development of oesophageal cancer. The aim of this study was to describe the role of LINC00958 in ESCC. Bioinformatics and real-time quantitative polymerase chain reaction (RT-qPCR) methods were utilized to predict and verify the expression of LINC00958 in ESCC. Related functional experiments, including cell proliferation, migration and invasion, were performed. In addition, a western blot and a dual luciferase reporter gene experiment were used to study the detailed carcinogenic mechanism of LINC00958. The results indicated there was a high expression of LINC00958 in ESCC, which promoted proliferation, migration, invasion and Epithelial-Mesenchymal Transition (EMT) of ESCC cells, and this effect may be via regulating miR-510-5p.

Effect of high-temperature and microwave expanding modification on reactivity of coal char for char-NO interaction.

Coal-fired industrial boiler has become a large source of atmospheric pollutants in China, urging to achieve low NOx emissions. This paper adjusts the coal char structure with high-temperature/microwave expanding modification to investigate the char-NO interaction. The results show that after high-temperature or microwave expansion, the pore structure of char is further expanded with more new pore structure of 2-12 nm. The proper expansion temperature/power/treatment-time increases the ablation collapse of char pores and the order of carbon structure. With microwave, COC and CO bands break, forming a large amount of aromatic CC unsaturated carbon atoms, incrseasing the surface active sites of char-NO interaction. The optimum modifications of char-NO reactivity are 800 °C-90 s and 960 W-90 s. The reduction rate of NO by microwave modified char decreases with increase of inlet NO (<1200 ppm), and increases with increase of inlet CO (<8000 ppm). Burnout time of microwave modified char is shortened, with more rapid release of NO and larger conversion rate of char-N to NO. With microwave field, the conversion rate of char-N to NO at 900 °C is more significant than that at 600 °C. The too large microwave power cannot further shorten the char burnout time and the release time of NO.

Roles of Ion-Exchangeable Sodium in the Conversion Process of Tar to Soot during Rapid Pyrolysis of Two Brown Coals in a Drop-Tube Reactor.

In this work, two series of brown coals (including acid-washed coal and ion-exchangeable Na-loaded coal) were pyrolyzed in a drop-tube reactor. The experimental results revealed that soot and tar yields of Na-loaded coals were significantly lower than that of acid-washed coals. Gasified Na can reduce the formation of big soot agglomerates. During coal primary pyrolysis, ion-exchangeable Na can reduce the amount and aromaticity of primary tar. Na released with volatiles can catalyze the cracking of aliphatic and aromatic compounds, inhibit the polymerization between aromatic rings, and promote the combination of soot/tar with oxygen-containing substances, resulting in the decrease of graphite crystallite size and the increase of amorphous carbon content. Na can also reduce the organization degree of soot by forming intercalation compounds.

Targeting macrophage checkpoint inhibitor SIRPα for anticancer therapy.

The CD47/signal regulatory protein α (Cd47/SIRPα)interaction provides a macrophage immune checkpoint pathway that plays a critical role in cancer immune evasion across multiple cancers. Here, we report the engineering of a humanized anti-SIRPα monoclonal antibody (1H9) for antibody target cancer therapy. 1H9 has broad activity across a wide range of SIRPα variants. Binding of 1H9 to SIRPα blocks its interaction with CD47, thereby promoting macrophage-mediated phagocytosis of cancer cells. Preclinical studies in vitro and in vivo demonstrate that 1H9 synergizes with other therapeutic antibodies to promote phagocytosis of tumor cells and inhibit tumor growth in both syngeneic and xenograft tumor models, leading to survival benefit. Thus, 1H9 can potentially act as a universal agent to enhance therapeutic efficacy when used in combination with most tumor-targeting antibodies. We report a comparison of anti-SIRPα and anti-CD47 antibodies in CD47/SIRPα double-humanized mice and found that 1H9 exhibits a substantially reduced antigen sink effect due to the limited tissue distribution of SIRPα expression. Toxicokinetic studies in nonhuman primates show that 1H9 is well tolerated, with no treatment-related adverse effects noted. These data highlight the clinical potential of 1H9 as a pan-therapeutic with the desired properties when used in combination with tumor-targeting antibodies.

Comparison between Arm Port and Chest Port for Optimal Vascular Access Port in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: This meta-analysis was conducted to compare the complication rates between arm and chest ports in patients with breast cancer. Design and Data Sources. PubMed, Embase, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang database were used to perform a systematic review and meta-analysis of publications published from the inception of the database to 11, October 2019. Our search generated a total of 22 articles published from 2011 to 2019, including 6 comparative studies and 16 single-arm articles, involving 4131 cases and 5272 controls. Single-arm studies combined with comparative studies were also pooled and analyzed. Finally, subgroup analysis was performed to compare the rates of infection and thrombosis between these two ports. Eligibility Criteria. Included articles were research studies comparing complication rates of arm ports with chest ports in patients with breast cancer. Any review or meta-analysis article would be removed. Data Extraction and Synthesis. Demographic data and information for the following analysis were extracted. DerSimonian and Laird random effect meta-analysis was conducted to analyze comparative studies while Begg's and Egger's tests were used for assessment of publication bias. Meta-regression analysis was performed to explain the sources of heterogeneity. RESULTS: There was no difference in the risk of overall complications between arm and chest ports for comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with. CONCLUSIONS: This study indicated that the arm port might increase the risk of overall complication risks as well as the risk of catheter-related thrombosis compared with the chest port. However, these reported findings still need to be verified by large randomized clinical trials.

Isolation of T cell receptor specifically reactive with autologous tumour cells from tumour-infiltrating lymphocytes and construction of T cell receptor engineered T cells for esophageal squamous cell carcinoma.

BACKGROUND: T cell receptor-engineered T cells (TCR-Ts) therapy is a promising cancer treatment strategy. Nowadays, most studies focused on identification of high-avidity T cell receptors (TCRs) directed against neoantigens derived from somatic mutations. However, few neoantigens per patient could induce immune response in epithelial cancer and additionally many tumor-specific antigens could be derived from noncoding region. Autologous tumor cells (ATCs) could be unbiased stimulators in activating and enriching tumor-reactive T cells. However, it's unknown if T cells engineered to express TCRs isolated from tumor-reactive T cells enriched by ATCs have strong antitumor response. METHODS: In this study, multiple TIL fragments obtained from a patient with esophageal squamous cell carcinoma (ESCC) were screened for specific recognition of ATCs. Tumor-reactive TILs were enriched by in vitro repeated stimulation of ATCs and isolated based on CD137 upregulation. Subsequently, tumor-reactive TCR was obtained by single-cell RT-PCR analysis and was introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We found that phenotype and effect function of TIL fragments derived from different tumor sites were spatially heterogeneous. Of four TIL fragments, only TIL-F1 could specifically identify ATCs. Subsequently, we isolated CD8+ CD137+ T cells from pre- and post-stimulated TIL-F1 co-cultured with ATCs, and identified their most dominant TCR. This TCR was introduced into PBLs to generate TCR-Ts, which specifically identified and killed ATCs in vivo and in vitro. CONCLUSION: This strategy provides the means to generate tumor-reactive TCR-Ts for ESCC, which is especially important for patients without prior knowledge of specific epitopes and might be applied for other cancers.

Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications. Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC. Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers. Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.