| 1. |
- Liu, Lihui, et al.
(author)
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Ablation of ERO1A induces lethal endoplasmic reticulum stress responses and immunogenic cell death to activate anti-tumor immunity
- 2023
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In: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 4:10
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Journal article (peer-reviewed)abstract
- Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.
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| 2. |
- Liu, Lihui, et al.
(author)
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Dynamic toxicity landscape of immunotherapy for solid tumors across treatment lines
- 2023
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In: Journal of the National Cancer Center. - : Elsevier. - 2667-0054. ; 3:3, s. 186-196
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Journal article (peer-reviewed)abstract
- Objective: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1/ligand-1 (PD-1/PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and lymphocyte-activation gene-3 (LAG-3) have been widely studied and applied throughout the course of cancer treatment. This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines. Methods: In total, 155 cohorts comprising 24 539 eligible patients were included in the safety analysis. Trial name, registration number, cancer type, trial phase, clinical setting, trial design, regimen, dosing schedule, age, sex and ethnicity distributions, number of patients, number of treatment-related adverse events (trAEs), and number of treatment-related death were extracted. We defined a timeline from the neoadjuvant setting to the third-line setting. We also introduced a synthesizing principle for adverse event rates (SPAER) of immunotherapy to ensure the comparability and reliability across different treatment lines. The study protocol was registered and approved by the PROSPERO protocol review committee (CRD42021242368). Results: After excluding the neoadjuvant setting group, we observed a distinct reduction in the incidence of treatment-related adverse events (trAEs) with an advancement of the line of ICI treatment. The incidence of trAEs was negatively correlated with the line of treatment, irrespective of whether monotherapy or dual-ICI combination therapy was administered. Sensitivity analyses also confirmed the coincident negative correlations. Conclusion: In summary, using a timeline-based concept centered around treatment lines, we revealed the dynamic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.
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| 3. |
- Xiao, Chao, et al.
(author)
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RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer
- 2018
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In: Cancer Science. - : Blackwell Publishing. - 1347-9032 .- 1349-7006. ; 109:4, s. 1075-1087
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Journal article (peer-reviewed)abstract
- Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both two cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Besides, transfection with RBBP6 shRNA improved levels of G2-M phase arrest which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, tumor growth rate of nude mice in RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.
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| 4. |
- Zhang, Lixiu, et al.
(author)
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Advances in the Application of Perovskite Materials
- 2023
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In: NANO-MICRO LETTERS. - : SHANGHAI JIAO TONG UNIV PRESS. - 2311-6706. ; 15:1
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Research review (peer-reviewed)abstract
- Nowadays, the soar of photovoltaic performance of perovskite solar cells has set off a fever in the study of metal halide perovskite materials. The excellent optoelectronic properties and defect tolerance feature allow metal halide perovskite to be employed in a wide variety of applications. This article provides a holistic review over the current progress and future prospects of metal halide perovskite materials in representative promising applications, including traditional optoelectronic devices (solar cells, light-emitting diodes, photodetectors, lasers), and cutting-edge technologies in terms of neuromorphic devices (artificial synapses and memristors) and pressure-induced emission. This review highlights the fundamentals, the current progress and the remaining challenges for each application, aiming to provide a comprehensive overview of the development status and a navigation of future research for metal halide perovskite materials and devices.
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| 5. |
- Cui, Zhiyong, et al.
(author)
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Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica
- 2023
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Succinic acid (SA) is an important C4-dicarboxylic acid. Microbial production of SA at low pH results in low purification costs and hence good overall process economics. However, redox imbalances limited SA biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, we engineer the strictly aerobic yeast Yarrowia lipolytica for efficient SA production without pH control. Introduction of the reductive TCA cycle into the cytosol of a succinate dehydrogenase-disrupted yeast strain causes arrested cell growth. Although adaptive laboratory evolution restores cell growth, limited NADH supply restricts SA production. Reconfiguration of the reductive SA biosynthesis pathway in the mitochondria through coupling the oxidative and reductive TCA cycle for NADH regeneration results in improved SA production. In pilot-scale fermentation, the engineered strain produces 111.9 g/L SA with a yield of 0.79 g/g glucose within 62 h. This study paves the way for industrial production of biobased SA.
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| 6. |
- Dai, Wenbin, et al.
(author)
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Modelling Industrial Cyber-Physical Systems using IEC 61499 and OPC UA
- 2018
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Conference paper (peer-reviewed)abstract
- Industrial Cyber-Physical Systems (iCPS) are considered as the enabling technology for achieve Industry 4.0. One main characteristic of the iCPS is the information transparency to allow interoperability among various devices and systems. The OPC UA provides a common information model for connecting Industry 4.0 components. On the other hand, the IEC 61499 is commonly used as an executable modeling language for iCPS. The IEC 61499 function block network provides an abstract view of the system configuration. By combining IEC 61499 and OPC UA, a visual executable model for iCPS is completed. In this paper, the mapping between two standards are provided and a case study of the proposed mapping is given.
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| 7. |
- Dai, Wenbin, et al.
(author)
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Service-oriented data acquisition and management for industrial cyber-physical systems
- 2017
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In: Proceedings. - Piscataway, NJ : Institute of Electrical and Electronics Engineers (IEEE). - 9781538608371 ; , s. 759-764
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Conference paper (peer-reviewed)abstract
- With rapid improvement in information and communication technologies, industrial automation systems are under the revolution. Legacy industrial automation systems lack flexibility and interoperability due to multi-layered architecture. From industrial cyber-physical system point of view, a new system architecture is needed to allow vertical and horizontal integration between all devices and systems from enterprise level to sensor level. In this paper, a RESTful service-oriented architecture is proposed for industrial controllers. By adopting RESTful services over HTTP methods, better efficiency for data acquisition from sensors, actuators, and controllers is achieved. In addition, service-oriented device management for industrial controllers is also implemented along with data acquisition. The reference architecture experiments on a car manufacturing demonstration line
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| 8. |
- De Luca, Alberto, et al.
(author)
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On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types : Chronicles of the MEMENTO challenge
- 2021
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 240
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Journal article (peer-reviewed)abstract
- Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.
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| 9. |
- Ho, Yu-Fang, et al.
(author)
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Text-world annotation and visualization for crime narrative reconstruction
- 2018
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In: Digital Scholarship in the Humanities. - : Oxford University Press. - 2055-7671 .- 2055-768X. ; 34:2, s. 310-334
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Journal article (peer-reviewed)abstract
- To assist legal professionals with more effective information processing and evaluation, we aim to develop software to identify and visualize the key information dispersed in the unstructured language data of a criminal case. A preliminary model of the software, Worldbuilder, is described in Wang et al. (2016a, b). The present article focuses on explaining the theory and vision behind the computational development of the software, which has involved establishing a means to annotate discourse for visualization purposes. The design of the annotation scheme is based on a cognitive model of discourse processing, Text World Theory (TWT), which describes and tracks how language users create a dynamic representation of events (i.e. text-worlds) in their minds as they communicate. As this is the first time TWT has informed the computational analysis of language, the model is augmented with Contextual Frame Theory, among other linguistic apparatus, to account for the complexities in the data and its translation from text to visualization. Using a statement from the Meredith Kercher murder trial as a case study, we illustrate the efficacy of the augmented TWT framework in the careful and purposeful preparation of linguistic data for computational visualization. Ultimately, this research bridges Cognitive and Computational Linguistics, improves the TWT model’s analytical accuracy, and yields a potentially useful tool for forensic work.
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| 10. |
- Ho, Yufang, et al.
(author)
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Projecting (un)certainty : A text-world analysis of three statements from the Meredith Kercher murder case
- 2018
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In: English Text Construction. - : John Benjamins Publishing Company. - 1874-8767 .- 1874-8775. ; 11:2, s. 286-317
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Journal article (peer-reviewed)abstract
- This article uses Text World Theory (Werth 1999; Gavins 2007) in conjunction with VUE (Visual Understanding Environment) concept mapping software to analyze three statements from the trial of Amanda Knox, who was charged (along with her boyfriend, Raffaele Sollecito) with the murder of Meredith Kercher in 2007. We compare the cognitive patterns (i.e. text-worlds) as reflected in Knox’s statements and use the insights gained to guide an examination of their individual linguistic features and associated potential legal implications. In the first two dictated statements, Knox is projected as an actor responsible for the reported actions/events that implicate her in the crime, whereas in the third statement (handwritten in English), she is projected as a senser, presenting more prominent epistemic uncertainty and indicating bewilderment. Further micro-level linguistic comparison indicates signs of textual alteration in the first two statements, i.e. crucial text was altered and thus resulted in a change of meaning and legal significance.
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| 11. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 12. |
- Sun, Tao, et al.
(author)
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Empirical evidence that manganese enrichment accelerates decomposition
- 2021
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In: Agriculture, Ecosystems & Environment. Applied Soil Ecology. - : Elsevier. - 0929-1393 .- 1873-0272. ; 168
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Journal article (peer-reviewed)abstract
- Our understanding of the controls regulating the rate of litter decomposition is important for improving confidence in the parameterization of carbon cycle–climate feedbacks. Traditional conceptual models rely primarily on climate and lignin/N ratios as the main regulators of decomposition. Here we studied the effects of manganese (Mn) addition on long-term decomposition across 18 substrates in a laboratory incubation. Mn addition remarkably promoted later stage of decomposition, resulting into a smaller fraction of slowly decomposing litter. This dynamic is closely associated with the changes of activities of manganese peroxidase, an important enzyme with greater capacity for lignin degradation. Our findings suggest the necessity of incorporating the interaction of Mn and decomposition into biogeochemical models.
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| 13. |
- Wang, Jing, et al.
(author)
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The Visualisation of Cognitive Structures in Forensic Statements
- 2016
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In: Proceedings of iV2016. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467389426 - 9781467389433 ; , s. 106-111
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Conference paper (peer-reviewed)abstract
- Forensic statements are often unstructured, intricate, and thus difficult to interpret and assess. This is due to the varied nature and format of how interviews with victims, witnesses, or suspects are conducted. It is even more difficult for police investigators, lawyers or other legal practitioners to grasp intuitively and accurately the key information pertaining within the varied statements. This research investigates the opportunities in the convergence of linguistic approaches to extracting and reconstructing the cognitive structure, i.e. "Text-Worlds", in a statement, and the computerised operational settings for enabling effective and hopefully more accurate interpretation of forensic discourse through visualisation.
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