Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered considerable attention in recent years, owing to its precise spatiotemporal accuracy with minimal side ...effects. Recent research reveals that the combination of PDT and PTT exhibits a remarkable anti‐tumor efficacy compared to PDT or PTT alone, which has put forward the new requirements of multifunctional phototherapy agents with both high photosensitization and photothermal conversion efficiencies. Among the newly developed multifunctional agents, the ones with one or two 3‐dicycanovinylindan‐1‐one (IC) moieties as the acceptors attract much more attention, due to their long‐wavelength excitation and emission, as well as high phototherapy efficacies. Therefore, in this review, the latest advancement of multifunctional agents based on IC acceptor is summarized. Especially, we focus on the structure–property relationships of the agents, as well as their biomedical application in anti‐tumor therapy or image‐guided therapy. Our perspective on the further future development of this field is also discussed to conclude.
3‐Dicycanovinylindan‐1‐one has been recently widely used to construct multifunctional phototheranostic agent for fluorescence image‐guided simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT), due to its advantage in balancing electron‐withdrawing ability and spin‐orbit coupling. Herein, the design principle, structure–property relationship, biomedical application, as well as several challenges and opportunities of this type of phototheranostic agent are discussed in detail in this review.
The design of a biologically active photosensitizer that effectively combines chemotherapy and photodynamic therapy remains a significant challenge. This article introduces a DNA targeted ...biologically active photosensitizer, CQA, which integrates the DNA alkylating moiety chlormethine with a photosensitizing moiety. Through DNA damage experiments and molecular docking, CQA has been demonstrated to act as an effective DNA targeting and damaging chemotherapeutic agent via chlormethine. Meanwhile, CQA can substantially amplify the DNA damage under light irradiation. Such enhancement is attributed to the introduction of the anthraquinone group, which possesses good redox properties and acts as an electron acceptor to promote electron transfer. Consequently, CQA efficiently generates both type-I and type-II reactive oxygen species (ROS), exerting an excellent photodynamic therapy (PDT) effect. The antitumor efficacy of CQA has been validated via results from in vivo tumor growth experiments, H&E staining, and IHC analyses. The design of this study emphasizes targeted DNA damage and enhanced ROS generation, underscoring the crucial role of efficient synergistic chemo- and photodynamic therapy in advancing cancer treatment strategies.
The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part ...to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorectal cancers (CRCs) and mouse CRC models, ask how these interactions are altered in human tumor organoid (tumoroid) cultures, and functionally recapitulate human myeloid-carcinoma interactions in vitro. Tumoroid cultures suppress gene expression programs involved in inflammation and immune cell migration, providing a reductive platform for re-establishing carcinoma-immune cell interactions in vitro. Introduction of human monocyte-derived macrophages into tumoroid cultures instructs macrophages to acquire immunosuppressive and pro-tumorigenic gene expression programs similar to those observed in vivo. This includes hallmark induction of SPP1, encoding Osteopontin, an extracellular CD44 ligand with established oncogenic effects. Taken together, these findings offer a framework for understanding CRC-TME interactions and provide a reductionist tool for modeling specific aspects of these interactions.
A schematic illustration of the corresponding relationship between wax micro-structure characteristics in molecular dynamics simulation and pipeline.
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•Micro-structural ...characterization of adsorbed & suspended wax is revealed.•A method for calculating the distributions of two forms of wax is proposed.•Surfactants are the main cause of wax adsorption behaviour.•Exceeding the critical wax content results in wax adsorption failure.
As a key issue in the flow assurance of wax-containing crude oils, the microscopic mechanism of wax deposition in multiphase pipelines is still unclear. Based on macroscopic experimental data, two forms of crystallized wax have been found under an oil-water emulsion, including adsorbed wax on the interface of water droplets and suspended wax in the bulk oil phase, which are the important factors influencing wax deposition. However, the micro-formation mechanism of the adsorbed & suspended wax is not elucidated. In this work, molecular dynamics simulations are used to investigate the micro-structure characteristics of the adsorbed & suspended wax in the oil-water emulsion containing surfactant Span60. A method is proposed to quantitatively calculate the distributions of the adsorbed & suspended wax and the percentage of wax adsorption area at the oil-water interface. The results indicate that surfactant with the hydrophilic end will insert into the water phase and the trailing hydrophobic end stretching will point to the oil phase during co-crystallizing with wax molecules. Meanwhile, the interface tension is further reduced by tilting the adsorbed wax tail chain to enhance the adsorption stability. Based on the complicated influence of surfactants on wax adsorption, the quantitative distribution characteristics of the adsorbed & suspended wax in the oil-water emulsion are complex under different wax carbon numbers and surfactant/wax contents. This microscopic investigation of wax distribution in oil-water emulsion can support the establishment of better strategies for solving the wax deposition problem in multiphase flow.
This mixed-methods study investigates the design and instructional practices of massive open online courses (MOOCs) instructors within the learning environment to address the cultural diversity and ...learner personalization needs. Leveraging a grounded theory approach, the researchers analyzed two rounds of email interviews (n1= 25; n2=19) with MOOC and open education leaders about cultural sensitivity and personalization in MOOCs. Those interviews led to the formation of a 30-item online questionnaire completed by 152 MOOC instructors. While many of the MOOC instructors within the sample did not fully grasp the complex issues of cultural diversity, most made attempts to modify their instructional practices to accommodate cultural variances. To address cultural and linguistic differences, instructors added subtitles to video content and offered transcripts for video or audio content. Additionally, instructors were careful with language use and hand gestures, used simplified language, slowed their pace of speech, made the course content easy to navigate, limited text by leveraging (multi)media, and encouraged learners to translate and localize content for their peers. Furthermore, many instructors favored collaborative, small group learning; however, instructors could not agree on best practices to establish these groups. Implications and future directions for MOOC instructors and instructional designers are offered.
This study explores the activities, tools, and resources that instructors of massive open online courses (MOOCs) use to improve the personalization of their MOOCs. Following email interviews with 25 ...MOOC and open education leaders regarding MOOC personalization, a questionnaire was developed. This questionnaire was then completed by 152 MOOC instructors from around the world. While more than 8 in 10 respondents claimed heavy involvement in designing their MOOCs, only one-third placed extensive effort on meeting unique learner needs during course design, and even fewer respondents were concerned with personalization during course delivery. An array of instructional practices, technology tools, and content resources were leveraged by instructors to personalize MOOC-based learning environments. Aligning with previous research, the chief resources and tools employed in their MOOCs were discussion forums, video lectures, supplemental readings, and practice quizzes. In addition, self-monitoring and peer-based methods of learner feedback were more common than instructor monitoring and feedback. Some respondents mentioned the use of flexible deadlines, proposed alternatives to course assignments, and introduced multimedia elements, mobile applications, and guest speakers among the ways in which they attempted to personalize their massive courses. A majority of the respondents reported modest or high interest in learning new techniques to personalize their next MOOC offering.
Eleven carefully selected, peer-reviewed contributions from the Virtual Conference on Computational Science (VCCS-2016) are featured in this edited book of proceedings. VCCS-2016, an annual meeting, ...was held online from 1st to 31st August 2016. The theme of the conference was "Computational Thinking for the Advancement of Society" and it matched the paradigm shift in the way we think. VCCS-2016 was attended by 100 participants from 20 countries. The chapters reflect a wide range of fundamental and applied research applying computational methods.