Journal articles: 'Zi yang shu yuan' – Grafiati (2024)

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This paper focuses on exploring the relationship between the human body, mind, and the universe as seen in “Huai nan zi”, and identifying its integrated points. Through this, it seeks to gain insights into the essence of ancient Chinese philosophy and culture while finding clues to solve various problems that humanity faces today. In the first chapter, it delves into the interconnectivity of humans, the Tao, and the universe. Through the sentences in “Huai nan zi”, it examines the nature and principles of the universe that ancient Chinese people had explored. Clearly recorded within are the characteristics of time, space, and the relative properties of all things, such as Yin and Yang. These people would have awakened to the world with the intuition that they themselves are microcosms, parts and wholes of the Tao. In the second chapter, the theme of the recognition of light and the regression to the interior is dealt with. It discusses that in the process of irradiating the human body with light to return to a state of complete purification, or true brightness, countless repetitions overcome all kinds of physical discomforts, which then extend to the realm of the inner mind. In the third chapter, it discusses the world sensitivity of a sage, based on the ontological insights of the self and the material. In the “Yuan dao xun” section of “Huai nan zi”, it is emphasized that the satisfaction that humans actually have does not lie in the external material enjoyment, but rather, one can feel the tranquility of the mind again when one focuses on the inner peace. It argues that through this, one can experience the value and beauty of life and reach the boundary of a higher dimension.

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The article “Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics”, written by Xue-lin CHAO, Shu-zhen JIANG, Jian-wen XIONG, Jin-qiong ZHAN, Bo WEI, Chun-nuan CHEN, Yuan-jian YANG was originally published electronically on the publisher’s internet portal on June 2020 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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An overview of the history of Chinese calligraphy shows that many people in Tang Dynasty such as Zang Huaiguan(張懷瓘), Yu Shinan(虞世南), expressed very precise and philosophical views on calligraphy. Yet, there have already been discussions related to calligraphy in thr Eastern Han Dynasty before such in-depth views of calligraphy in Tang Dynasty. Yang Xiong(揚雄) has already clarified the espression of the mind of calligraphy by saying that 'Shu(書)〔originally a book, but later understood as a calligraphy〕is picture of the mind, which is composed of characters written with a brush. however, people that understood and practically applied it to calligraphy are the Cui Yuan(崔瑗) and Cai Yong(蔡邕) in the Eastern Han Dynasty. In「Caushushi(草書勢)」, Cui Yuan gave calligraphy an independent aesthetic value that deviated from practical functionality. Moreover, it contains content that shows the aftistry of the individual's self-awarenss. In order words, it describes the artistic characteristics of the cursive script through the origin of calligraphy, the occurrence of the cursive script and the feeling of the shape and its force of the cursive script. Cai Yong wrote「Bilun(筆論)」, and it says what kind of mindset and brushstroke is used in calligraphy creation to make calligraphy creation with true beauty possible. It is the so-called ‘calligraphy is an art that works on creation by relaxing the tension of the mind 〔書者, 散也〕’ In other words, it revealed for the first time what kind of mind could be conveyed through what kind of creative attitude and what kind of movement of the brush could be used to write truly beautiful writing. It shows that the recognized calligraphy in Taoist aesthetic thought. Cui Yuan and Cai Yong not only mentioned calligraphy techniques and the method of wielding brush related to actual calligraphy creation but also clarified what conditions must be met for calligraphy to become a magnificent art. Such remarks by Cui Yuan and Cai Yong contain. the contents of understanding calligraphy through the taoist philosophy, on their views. Thus, from the perspective of calligraphy aesthetics, various andswers to the question 'what kind of art is calligraphy can be obtained through the views and perceptions of calligraphy by Cui Yuan, Zhao Yi and Cai Yong in the Eastern Han Dynasty.

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The Sanyuan Canzan Yanshou Shu 三元參贊延壽書, compiled by Li Pengfei during the Yuan dynasty, is a comprehensive collection of the essence of earlier health preservation literature. Recently, the Jianwen first-year (1399) re-engraved edition by Liu Yuanran 劉淵然 (1351–1432) has emerged, which is currently housed in the Imperial Household Agency Library in Japan. It has challenged the prevailing consensus in China that the edition (1445) in the Daozang 道藏 is the earliest version. This discovery not only enriches our understanding of the text’s historical dissemination but also highlights the international appreciation and preservation of Chinese traditional medical and health knowledge. Upon meticulous examination, the various editions of this text can be systematically classified into two distinct lineages: Yanshou Canzan 延壽參贊 and Canzan Yanshou 參贊延壽. The latter lineage is notably more comprehensive, with the Wanli 萬曆 edition serving as a prime exemplar of this expanded scope. Li Pengfei primarily drew upon the Yangsheng Leizuan 養生類纂 as the foundational text for his work, skillfully integrating a wealth of Daoism and medical scriptures. He adeptly restructured the content by employing the conceptual framework of three primes (sanyuan 三元), incorporating the health preservation philosophies of Confucianism and Buddhism, thereby transforming it into a more systematic and diverse Daoism scripture dedicated to health preservation. The book eloquently advocates for health-preserving philosophies centered around the principle of not diminishing (busun 不損) primordial pneuma (yuanqi 元氣), extending life through three primes, and prolonging life through the virtue of yin (yinde 陰德). These ideas emphasize a human-centered approach, focusing on preserving the primordial pneuma as the foundation and employing both loss prevention and supplementation as dual pathways. It aims to achieve a state of health preservation where there is unity of man with heaven (tianren heyi 天人合一) and a harmonious balance of yin and yang energies (yinyang qihe 陰陽氣和).

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Shakespeare studies in Mainland China and Taiwan evolved from the same origin during the two centuries after Shakespeare being introduced into China in the early nineteenth century. Although Shakespeare was first seen on the Taiwan stage in the Japanese language during the colonial period, it was after Kuomintang moved to Taiwan in 1949 that Shakespeare studies began to flourish when scholars and theatrical experts from mainland China, such as Liang Shih-Chiu, Yu Er-Chang, Wang Sheng-shan and others brought Chinese Shakespeare to Taiwan. Since the 1980s, mainland Shakespeareans began to communicate actively with their colleagues in Taiwan. With the continuous efforts of Cao Yu, Fang Ping, Meng Xianqiang, Gu Zhengkun, Yang Lingui and many other scholars in mainland China and Chu Li-Min, Yen Yuan-shu, Perng Ching-Hsi and other scholars in Taiwan, communications and conversations on Shakespeare studies across the Taiwan Strait were gradually enhanced in recent years. Meanwhile, innovations in Chinese adaptations of Shakespeare have resulted in a new performing medium, Shake-xiqu, through which theatrical practitioners on both sides explore possibilities of a union of Shakespeare and traditional Chinese theatre. This paper studies some intricate relationship in the history of Shakespeare studies in mainland China and Taiwan from a developmental perspective and suggests opportunities for positive and effective co-operations and interactions in the future.

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Traditional Chinese herbal products (CHPs) have been described in ancient medicine systems as treatments for various stroke-associated ailments. This study is aimed to investigate the prescription patterns and combinations of CHPs for ischemic stroke in Taiwan. Prescriptions of CHPs for ischemic stroke were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan. Every prescription with a leading diagnosis of ischemic stroke made during 2000–2010 was analyzed. Descriptive statistics were applied to the pattern of co-prescriptions. Multiple logistic regression models were used to assess demographic and risk factors that are correlated with CHP use. The dataset of inpatient claims data contained information on 15,896 subjects who experienced ischemic stroke from 2000 to 2010. There was an average of 5.82 CHPs in a single prescription for subjects with ischemic stroke. Bu-yang-huan-wu-tang (BYHWT) (40.32%) was by far the most frequently prescribed formula CHP for ischemic stroke, and the most commonly used combination of two-formula-CHP was BYHWT with Shu-jin-huo-xue-tang (SJHXT) (4.40%). Dan Shen (16.50%) was the most commonly used single CHP for ischemic stroke, and the most commonly used combination of two single CHPs was Shi Chang Pua with Yuan Zhi (4.79%). We found that BYHWT and Dan Shen were the most frequently prescribed formula and single CHP for ischemic stroke, respectively. These results provide information about individualized therapy and may contribute to further pharmacologic experiments and clinical trials.

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This paper is to sort out the content and explore the characteristics of the three research works on “Shangshu” of Yuhui (柳僖, 1773-1837), a Confusion scholar in the late Joseon Dynasty. ShinChak(申綽), a famous scholar of textual research in the late Joseon Dynasty, mentioned in a letter to ChongYak-Yong(丁若鏞) that Yuhui’s textual research on “Guwen Shangshu古文尙書” was meticulous and detailed. He also praised Yuhui's very high attainment in interpreting “Chunqiu 春秋” in “Taegyosingi胎敎新記序”. However, as Yuhui’s works on Confucian classics were not included in several famous Korean series such as “The Complete Collection of the Korean Study of Confucian Classics韓國經學資料集成”, “Korean Literary Collections in Classical Chinese韓國文集叢刊”, “Korean Anthology in History韓國歷代文集叢書”, and they were not published in separate volumes, they have received little attention from the academic circles. Based on “Yuhui Chronicle”, Yuhui's personal notes and many other clues, this paper first speculates that Yuhui's publications should have the following sequence: firstly “SangSeoKoGeummoonSongEui尙書今古文訟疑”(1824), then “SeoChaejeonboseol書蔡傳補說”(presumably written between 1824-1825), to be followed by “SeoGo書詁”(written after August 1825). In addition, his “Shangshu” theory has the following characteristics and significance: 1. Analysis based on textual research: In the debate on ancient prose, if ChongYak-Yong is compared to Yan Ruoqiu(閻若璩), Yuhui can be compared to Mao Qiling(毛奇齡). The reason is that those who supported the ancient text “Shangshu” in the Joseon Dynasty mostly refuted the study of school examination because of the sixteen-character mentality. They think analysing the classics through textual research is like “trusting the leaves and query the root” and is a waste of effort. However, Yuhui’s method of analysing classics was different from that of the predecessors. He adopted textual research, going through systematically the historical records of the past dynasties and the theories of the predecessors one by one. At the same time, Yuhui often cited Mao Qiling's theory as his own supporting evidence, which is very different from the previous Korean scholars who belittled Xihe. 2. Interpreting the classics through linguistics: Due to innate factors, Korean Confucianists seldom used the convenience of geographical location to discuss the authenticity of the ancient “Shangshu” like the Ming and Qing scholars who adopted the methods of geographical research and ancient and modern phonetics. Instead, they defended the ancient text “Shangshu”. based on viewpoints such as “the words of the sages are inviolable”, “as Zhu Zi never said this is a fake book, it must be authentic”, “the meaning is correct, so it is not a fake book”. In addition to Yuhui's method of textual research to affirm his own views, it can also be seen that Yuhui used his expertise in Guoyinxue to explain the classics. For example, on the issue of Fu Sheng's dictation of the classics, Yuhui not only pointed out that similar characters might have caused errors, but also cited examples of errors caused by sounds. 3. Revising and supplementing “Shu Ji Zhuan書集傳”: Although “Shu Ji Zhuan” has been standing for hundreds of years since the Yuan Dynasty, there have been views of support and opposition since its compilation at the end of the Song Dynasty. Yuhui's “SeoChaejeonboseol” and “SeoGo” show that Korean Confucianists did not completely stick to the “Shu Ji Zhuan” which represents Zhu Xi's last will and would also identify the mistakes and suggest amendments to the text when the meaning was not clear. 4. Compilation of lost merits: Many ancient theories are quoted in the three works, such as those of Ma Qianluan馬遷鸞 from the Song Dynasty and Li Pan李槃 from the Ming Dynasty, which is very rare. If “MunTong文通” can be organized and understood,

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Abstract Background: Medulloblastoma (MB) is the most common children’s malignant brain tumor. Although MB can be treated with conventional chemotherapies, chemoresistance has been frequently developed and thereby hampers their therapeutic effectiveness. The preliminary reports of our research showed that some heat shock proteins have higher levels in MB cells. Among these heat shock proteins, HSP70 and HSP90 expressions are particularly high in MB CD133+ cancer stem cells (CSCs), which arouses our attention and interest. Numerous studies demonstrated that heat shock proteins are prominent in some chemotherapy-resistant cancer cells and CSCs. As known HSP90 and its client proteins are required for the maintenance of self-renewal/stemness and regulation of cell cycle, synergistic killing of cancer cells by simultaneous inhibition of HSP90 expression and activity may be a considerable good therapeutic strategy for treating MB. The purpose of this study is to verify the regulatory function of HSP90 in chemoresistance and stemness of MB. Materials and Methods: The levels of HSP90, its client proteins (P13K/pAKT, Erk, NFκB, and c-Myc), and stemness makers were detected using immunoblotting and immunoprecipitation after the treatment of HSP90 inhibitor (17-AAG) or knockdown of HSP90 by siRNA in MB and MB CSCs. The antitumor effects of HSPs inhibitors or knockdown of HSPs on these cells were evaluated by MTT assay, Annexin V/PI analysis and cell cycle analysis. Results: Our findings revealed elevated expression of HSP90 and its target client proteins in MB cells compared to normal astrocytes. Silencing or inhibiting HSP90 expression induced cell cycle arrest in MB cells. Notably, CD133+ MB CSCs exhibited higher HSP90 levels than parental MB cells. Inhibition of HSP90 led to reduced sphere formation and expression of stemness markers in CD133+ MB CSCs. Treatment with 17-AAG demonstrated antitumor activity in CD133+ MB CSCs, and a synergistic effect was observed when combining conventional chemotherapeutic agents with 17-AAG in MB cells Conclusion: These results illustrated that inhibition of HSP90 could eliminate CSCs, and thereby overcome resistance to chemotherapeutic agents in MB. Chemotherapies in combination with HSP90 blockade may be an emerging MB therapy in the future. Citation Format: Shu-Mei Chen, Hsieng-Yun Huang, Chien-Kai Wang, Yi-Yuan Yang, Sy-Jye Leu, Ying-Ying Li. Exploring the impact of heat shock protein 90 on the antitumor efficacy and stemness in medulloblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 152.

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Abstract Despite advancements of immunotherapy against various cancers, breast cancer still retains poor response to immune checkpoint blockade (ICB) therapy. Therefore, the identification of promising target or new strategy to enhance ICB therapy in breast cancer is crucial. Here, we uncover that the DNA-damaging potential of tamoxifen (TAM) can shape the unfavorable but ready-to-fire tumor immune microenvironment in breast cancer. We discover that a long-term TAM administration unexpectedly induces JAK/STAT signaling and Type I interferon (IFN)-stimulated gene expression to promote T-cell infiltration. Furthermore, TAM also induces the expression of CEACAM1, which acts as an alternative T-cell inhibitory ligand via binding to TIM-3, a “checkpoint” receptor expressed on CD4+ and CD8+ T cells. The chromatin ‘‘reader’’ RACK7/ZMYND8, which functions as a transcriptional repressor of IFN-stimulated gene (ISG) and a critical factor in DNA repair, is found to be downregulated upon tamoxifen exposure and involved in the tamoxifen-mediated cellular modulation. We demonstrate that TAM in conjunction with RACK7-knockdown (KD) triggers robust upregulation of ISGs and CEACAM1 in both estrogen receptor-positive (ER+) and triple negative breast cancer (TNBC) cells. This immunomodulatory effect lead by loss of RACK7 is specific to TAM treatment, and is not observed when combined with other endocrine therapeutics. TAM combined with RACK7-KD promotes mitochondrial DNA damage, which leads to accumulation of cytosolic DNA and subsequent activation of the cGAS/STING pathway. The murine breast orthotopic models with TS/A, EO771 and 4T1 cells further demonstrate that TAM-mediated immunomodulatory in conjunction with RACK7-KD evokes cytokine/chemokine secretion and further induces T-cell infiltration into tumor microenvironment. However, the tumor killing effect is limited due to promotion of T-cell exhaustion from CEACAM1-TIM-3 interaction between tumor and T cells. Thus, our study indicates that targeting CEACAM1-TIM-3 interaction is crucial for TAM-mediated tumor immune response. This brings promising therapeutic approach with TAM by combining RACK7-KD with blockage to CEACAM1-TIM-3 interaction in breast cancer. The resistance of tamoxifen treatment may be overcome, and RACK7 may serve as both a therapeutic target and a biomarker to enable ICB therapy. Citation Format: Marvin A. Aberin, Yu-Ling (Pony) Lee, Xin-Guo Hsu, Chen-Yang Shen, Yao-Ming Chang, Kun-Yuan Lin, Chandan Guha, Shu-Ping Wang. New functional role of tamoxifen in breast cancer immunomodulation: role of RACK7 in activation of type I interferon signaling and CEACAM1/TIM-3-dependent immunosuppression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3646.

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Abstract Tamoxifen is a widely known estrogen receptor (ER) modulator which has been employed in adjuvant treatment of ER+ breast cancer for over 30 years. Interestingly, clinical observations reveal that tamoxifen is capable of inducing regression of some tumors lacking ER expression whereas tamoxifen is also capable of increasing host resistance against cancer in an ER-independent mechanism. These findings suggest the immunomodulatory effects of tamoxifen may be ER-independent, but little is known about the underlying mechanism and the potential clinical implication. Recently, we identified a novel mechanism by which tamoxifen exerts its DNA-damaging potential by re-shaping the unfavorable tumor microenvironment in breast cancer. A long-term tamoxifen administration induces downregulation of the chromatin ‘‘reader’’ RACK7/ZMYND8, which acts as a suppressor of interferon-stimulated genes (ISGs, including cytokines and chemokines) and CEACAM1 in both ER+ and triple negative breast cancer (TNBC) cells. To investigate the immunomodulatory effects of tamoxifen in conjunction with RACK7-knockdown, the orthotopic murine TNBC 4T1 model was employed to investigate tamoxifen-mediated cellular modulation in TNBC. The control and RACK7-knockdown 4T1 cells are orthotopically implanted into the mammary fat pad of female BALB/c mice. Peripheral cytokines/chemokines and high-content biomarker studies (multiplex immunoassays, flow cytometry, and single-cell RNA sequencing) are deployed to obtain insights into the mechanistic rationale behind the immunomodulatory effects of tamoxifen and/or RACK7-knockdown. The tamoxifen-mediated cellular modulation evokes cytokine/chemokine secretion and further induces T-cell infiltration into tumor area. However, tumor reduction was limited due to extensive T-cell exhaustion from interaction of CEACAM1 and TIM-3, a “checkpoint” receptor expressed in CD4+ and CD8+ T cells. The expression patterns of CEACAM1 and PD-L1 in 4T1 tumor cells and that of TIM-3 and PD-1 in CD4+ and CD8+ T-cells correlate with intra-tumor infiltration of T-cells and tumor cell growth. Therefore, targeting the interaction between CEACAM1 and TIM-3 to overcome T-cell exhaustion is crucial for the new therapeutic role of tamoxifen treatment in TNBC breast cancer in conjugation with RACK7-knockdown. Altogether, our findings provide direct evidence to support a new therapeutic opportunity by targeting CEACAM1-TIM-3 interaction in the tamoxifen-mediated tumor immune microenvironment for improving immune checkpoint blockade therapy in breast cancer. Citation Format: Pony Yu-Ling Lee, Marvin A. Aberin, Chien-Chang Shen, Kun-Yuan Lin, Chao Di Chang, Chih-Chieh Yang, Shan-Yun Cheng, Ya Wen Hung, Xin-Guo Hsu, Shu-Ping Wang. Reshaping the tumor microenvironment: new application of tamoxifen in triple negative breast cancer immunomodulation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5953.

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Abstract Breast cancer brain metastasis is one of the most common forms of breast cancer metastasis and a major cause of morbidity and mortality. Patients who develop brain metastases tend to be associated with progressive neurologic deficits and short overall survival, which represents an unmet medical need. Extensive research has been conducted to elucidate the mechanism of cancer metastasis with limited information gained as to how cancer cells extravasate and colonize to the brain. Recently, we identified a novel mechanism by which squalene epoxidase (SQLE), the second rate-limiting enzyme in cholesterol biosynthesis, plays a critical role in the process of breast cancer metastasis to the brain. Thus, toward a better understanding of the underlying molecular mechanisms and applications of molecular target(s) for brain metastasis therapy, murine models were employed for investigation of brain extravasation and colonization with intracardiac or direct intracranial injections of GFP/FLuc-labeled human MDA-MB-231 metastatic breast carcinoma cells. The MDA-MB-231 cells were found to metastasize to the brain and other organs following intracardiac implantation into nude mice and were further isolated from each tissue. Interestingly, the isolated brain-metastasized tumor cells (MDA-MB-231-BrM) exhibited a significant upregulation of SQLE expression when compared with those that metastasized to other distal sites. The essential role of SQLE in the specific steps of the breast cancer-to-brain metastatic process was evaluated by ex vivo immunofluorescence analysis and immunohistochemistry staining of brain slices from the study subjects. Our data demonstrate that high SQLE expression is essential for MDA-MB-231-BrM to extravasate into the parenchyma, as well as the formation of micro- and macro-metastases in the brain. Interestingly, we found that blood vessel co-option and the surrounding neuronal cells play key roles in supporting MDA-MB-231-BrM to develop brain macro-metastases. In vitro blood-brain barrier (BBB) models further demonstrated the critical role of SQLE in promoting tumor cell invasion and penetration through the BBB. To verify SQLE as an oncogenic factor that can be selected as a potential therapeutic target in suppressing breast cancer brain metastasis, we evaluated the inhibitory effects of terbinafine (a SQLE inhibitor) in both the MDA-MB-231-BrM orthotopic and intracardiac mouse models. Pharmacologic inhibition of SQLE by terbinafine suppressed MDA-MB-231-BrM tumor growth at the mammary fat pad and distal metastases to the brain, suggesting that targeting SQLE represents a therapeutic opportunity for breast cancer brain metastasis. Citation Format: Pony Yu-Ling Lee, Kun-Yuan Lin, Chao-Di Chang, Shan-Yun Cheng, Ya-Wen Hung, Chih-Chieh Yang, Yu-Hsien Chang, Chien-Chang Shen, Jia-Yun Yeh, Yung-Lung Yu, Shu-Ping Wang. Targeting squalene epoxidase for breast cancer brain metastasis: The evaluation of a new therapeutic target for brain extravasation and colonization using animal models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1449.

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Abstract Brain metastases are serious complications of breast cancer, especially in triple-negative breast cancer (TNBC) patients. There is currently no effective treatment due to the unique brain microenvironment and limitation for drugs to cross the blood-brain barrier (BBB). BBB limits access of nutrients from the circulation and thereby makes the brain hypoxic and depleted of metabolites, growth factors and proteins. However, it remains poorly understood how breast cancer cells manipulate for adaption and colonization in the brain. To probe the molecular mechanism of breast cancer brain metastasis (BCBM), we compared gene signatures in primary breast tumors and BCBM tumors, and identified that SQLE (encodes squalene epoxidase, the second rate-limiting enzyme in the cholesterol biosynthesis) could be a leading-edge gene in breast cancer brain metastasis. To explore the role of SQLE in BCBM, we established the brain metastatic TNBC MDA-MB-231 (MDA231-BrM) cell line from brain metastatic subpopulation that originated from its parental MDA-MB-231 (MDA231) cell line. We found that SQLE expression was greatly upregulated in MDA231-BrM cells compared with the parental MDA231 cells. Using MDA231-BrM and MDA231 cell lines expressing SQLE shRNAs, we evaluated the effects of SQLE loss on cancer cell migration, invasion, and stemness by wound-healing, transwell invasion/migration, and tumorsphere formation assays. While loss of SQLE greatly attenuated cell invasiveness and stemness in both MDA231 and MDA231-BrM cells, loss of SQLE could only affect the cell migration activity on MDA231 cells but not MDA231-BrM cells. Our RNA-seq data further identified a subset of SQLE-affected genes that is uniquely enriched in MDA231-BrM cells and favors brain extravasation and colonization. To explore the potential function of SQLE in brain extravasation and colonization, we established in vitro BBB models and ex vivo mouse brain slice organotypic cultures. We showed that loss of SQLE inhibited the ability of MDA231-BrM cells to across the BBB-mimic astrocyte-endothelial structures as well as impaired the co-option with blood capillaries in the mouse brain slices. Although SQLE-deficient MDA231-BrM cells could still spread on the surface of the blood vessels, they seemed to undergo apoptosis. Since the ability to invade, migrate, and penetrate is critical for invasion of cancer cells, our results strongly imply the novel function of SQLE in breast cancer cell invasion, penetration, and even colonization in the brain through blood vessel co-option. In summary, our data reveal a novel role for SQLE in two critical requisites for breast-to-brain extravasation and colonization - the ability to penetrate through BBB and to co-opt brain vessels for metastatic expansion. Our findings indicate that targeting SQLE may represent a therapeutic opportunity for breast cancer brain metastases. Citation Format: Shu-Ping Wang, Jia-Yun Yeh, Yu-Ling (Pony) Lee, Kun-Yuan Lin, Chao-Di Chang, Chih-Chieh Yang, Shan-Yun Cheng, Ya-Wen Hung, Yu-Hsien Chang, Yao-Feng Li, Yung-Lung Yu. Identification of a novel squalene epoxidase function in breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1550.

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Abstract Background: Breast cancer is one of the most common malignant tumors in women worldwide. In China, the incidence of breast cancer has been steadily increasing. Approximately 30% of human breast cancers exhibit human epidermal growth factor receptor 2 (HER2) positivity, which is closely associated with tumor aggressiveness, high recurrence rate and high mortality. This study aimed to evaluate the efficacy, safety, and immunogenicity of TQ-B211 (a trastuzumab biosimilar) compared to the reference trastuzumab in combination with docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer. Methods: This randomized, multicenter, double-blind phase III equivalence study enrolled HER2+ metastatic breast cancer patients aged 18-75, ECOG PS ≤1, no prior systemic chemotherapy, biologic, or targeted therapy for recurrent or metastatic disease, and at least one measurable lesion (RECIST 1.1). The patients were randomly assigned to two groups: the experimental group received TQ-B211 (8 mg/kg iv on day 1, cycle 1, followed by 6 mg/kg q3w for cycles 2-8) in combination with docetaxel (75 mg/m2 on day 2, cycle1, followed by 75 mg/m2 on day 1 for cycles 2-8), while the control group received Herceptin® in combination with docetaxel. For subjects who completed 8 cycles of treatment without disease progression and demonstrated tolerability, they were subsequently administered TQ-B211 as monotherapy until disease progression or unsuitable for further treatment. The primary efficacy endpoint was ORR up to week 24 (ORR24w). Equivalence was declared if the 90% confidence interval (CI) of relative ratio (RR) value was within the range of 0.8 to 1.25. Secondary efficacy endpoints included duration of response (DoR); progression-free survival (PFS); disease control rate (DCR); overall survival (OS), safety and immunogenicity. Results: Between December 6, 2018 and July 31, 2021, a total of 386 patients (pts) were enrolled (192 pts in the TQ-B211 group and 194 pts in the Herceptin® group). In the intention-to-treat (ITT) population, the ORR24w of the TQ-B211 group was 67.19% (95% CI: 60.55, 73.83), while the ORR24w of the Herceptin® group was 65.98% (95% CI: 59.31, 72.65). The RR of the confirmed ORR24w between the two groups was 1.02 (90%CI, 0.90, 1.15), which fell entirely in the predefined equivalence margins (0.8, 1.25), indicating comparable efficacy of the two drugs. In the ITT population, the DCR of the TQ-B211 group and the Herceptin® group were 83.85% (78.65, 89.06) and 78.35% (72.56, 84.15) respectively, with no statistically significant difference between the two groups (P=0.1940). By the data cutoff date of October 31, 2021, the median PFS was not statistically different (P=0.6834); the median OS was not reached in both groups (P=0.9246). Additionally, the data results of the per-protocol (PP) population were similar to those of the ITT population. In total, similar rates of treatment-related grade ≥3 adverse events (41.05% vs. 46.39%) occurred in the TQ-B211 and Herceptin® groups, respectively. The incidence and magnitude of immunogenicity were low in both of the two groups (ADA: 0.53% vs. 0%, Nab: both negative). Conclusion: Equivalence for efficacy was demonstrated between TQ-B211 and Herceptin® on the basis of ORR24w. Safety and immunogenicity were comparable. Citation Format: Xichun Hu, Qingyuan Zhang, Shusen Wang, Tao Sun, Xiaohua Zeng, Weimin Xie, Zhongsheng Tong, Hui Cao, Huihua Xiong, Xiuwen Wang, Jin Yang, Shuqun Zhang, Ying Wang, Chunhong Hu, Kaijian Lei, Binlin Ma, Wei Liu, Zhiyong Yu, PeiJian Peng, Hongwei Yang, Zhijun Yuan, Xiaojia Wang, Xujuan Wang, Hong Wang, Yongqian Shu, Nanlin Li, Wenbin Yue, Jingfen Wang, Daqing Wang, Zhiguo Luo, Junyang Mo, Yarong Li, Lili Sheng. Efficacy, Safety, and Immunogenicity of TQ-B211 (a Trastuzumab Biosimilar) Plus Docetaxel versus Herceptin® Plus Docetaxel for HER2-positive Metastatic Breast Cancer: a Double-blind, Randomised, Multicenter, Phase 3 Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-03.

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BACKGROUND: Hypertension has become one of the most pathogenic diseases in the world. OBJECTIVE: This paper summarizes and analyzes the acupuncture point combinations and treatment principles of acupuncture for hypertension in a systematic way by means of big data mining. METHODS: The literature for this paper was obtained from CNKI, Wanfang, VIP, SinoMed and PubMed, Embase, Cochrane Library, Web of Science, and Ovid databases. Thedata were collected to obtain combinations of acupoints with strong associations through association rule analysis, complex networks for screening to obtain core acupoint nuclei, and cluster analysis to derive treatment principles. RESULTS: A total of 127 acupuncture prescriptions involving 66 acupoints were included in this study. Tai-chong (LR3), Qu-chi (LI11), Zu-san-li (ST36), Feng-chi (GB20), and He-gu (LI4) were the most commonly used acupoints. The large intestine meridian was the preferred meridian, and most of the extremity acupoints, especially the lower extremities, were selected clinically. The association rule reveals that Qu-chi (LI11) and Zu-san-li (ST36) are the dominant combination acupoints. 3 core association points obtained after complex network analysis, the 1st association, Bai-hui (DU20), Tai-xi (KI3), Gan-shu (BL18), Shen-shu (BL23); The 2nd association, Qu-chi (LI11), He-gu (LI4), San-yin-jiao (SP6), Zu-san-li (ST36), Feng-chi (GB20), Tai-chong (LR3); The 3rd association, Qi-hai (RN6), Guan-yuan (RN4), Zhong-wan (RN12), Zhao-hai (KI6), Tai-yang (EX-HN5), Lie-que (LU7), Yang-ling-quan (GB34), Xing-jian (LR2), Yin-ling-quan (SP9). Cluster analysis yielded the treatment principles of nourishing Yin and submerging Yang, pacifying the liver and submerging Yang, tonifying Qi and Blood, and calming the mind and restoring the pulse, improving clinical outcomes. CONCLUSION: By means of big data mining, we can provide reference for acupuncture point grouping and selection for clinical acupuncture treatment of hypertension.

Abstract:

AbstractXiang‐Yang Zeng, Xiao‐Yan Jiang, Jia‐Hui Yong, Hui Xie, Jing Yuan, Da Zeng, Ying‐Yu Dou, Song‐Shu Xiao “lncRNA ABHD11‐AS1, regulated by the EGFR pathway, contributes to the ovarian cancer tumorigenesis by epigenetically suppressing TIMP2” Cancer Med. 2019; 8: 7074–7085 (https://doi.org/10.1002/cam4.2586)The above article, published online on 30 September 2019, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor‐in‐Chief, Stephen Tait, and John Wiley and Sons Ltd. Following publication, concerns were raised by a third party regarding image overlap within Figure 2b. Furthermore, several figure elements have been published elsewhere, identifying the cells as originating from different cell lines and subjected to different treatment. The authors did not respond to the concerns raised and did not provide the original data. The editors consider the results and conclusion reported in this article unreliable.

Abstract:

Золь-гель метод применен для получения одно- и двойнослойных оксидно-алюминиевых пленок на поверхности конструкционной стали 08кп для защиты от коррозии. Золь-гель систему готовили по методу Йолдаса путем гидролитической поликонденсации изопропоксида алюминия в присутствии уксусной кислоты при температуре 85-90 °С. Измерены рН, размер и дзета-потенциал частиц бемита, а также изучено коррозионное поведение стали в полученных коллоидах. При комнатной температуре слой гидрогеля бемита наносили путем погружения образцов стали в гель, выдержки в нем и последующей сушки в присутствии паров аммиака с целью подавления коррозии.Термообработку при 500 °С в атмосфере воздуха применяли для разложения бемита с образованием оксида алюминия и закрепления пленки на поверхности субстрата. Второй слой пленки наносили аналогичным образом поверх полностью сформированного первого слоя. Морфология поверхности полученных пленок изучена методами сканирующей электронной и атомно-силовой микроскопии. Электрохимические методы исследования – потенциометрия, вольамперометрия и электрохимическая импедансная спектроскопия были применены для сопоставительного исследования противокоррозионных свойств одно-и двойнослойных оксидно-алюминиевыхпокрытий на стали в 3.5 %-ном растворе хлорида натрия. Показано, что покрытия, полученные по описанной схеме, обладают хорошей адгезией к поверхности стали. По сравнению с контрольным образцом для стальных электродов с покрытием характерно смещение стационарногопотенциала более чем на 0.6 В, а начало активного электрохимического окисления - более чем на 1 В в положительном направлении. Происходит изменение кинетики анодных и катодных процессов, что в совокупности приводит к снижению коррозионного тока более чем на 2 порядка.Применение метода электрохимической импедансной спектроскопии позволило установить 2.5 часовую высокую противокоррозионную эффективность двойнослойного оксидно-алюминиевого покрытия на стали в растворе хлорида натрия. 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Abstract:

IntroductionWhat can we learn about anomaly from the strangeness of a puppet, a lifeless object, that can both bleed and die? How does the filming process of a puppet’s death engage across media and produce a new media genre that is not easily classified within traditional conventions? Why do these fighting and bleeding puppets’ scenes consistently attract audiences? This study examines how Pili puppetry (1984-present), a popular TV series depicting martial arts-based narratives and fight sequences, interacts with digital technologies and constructs a new media genre. The transmedia constitution of a virtual world not only challenges the stereotype of puppetry’s target audience but also expands the audience’s bodily imagination and desires through the visual component of death scenes. Hence, the show does not merely represent or signify an anomaly, but even creates anomalous desires and imaginary bodies.Cultural commodification and advancing technologies have motivated the convergence and displacement of traditional boundaries, genres, and media, changing the very fabric of textuality itself. By exploring how new media affect the audience’s visual reception of fighting and death, this article sheds light on understanding the metamorphoses of Taiwanese puppetry and articulates a theoretical argument regarding the show’s artistic practice to explain how its form transverses traditional boundaries. This critical exploration focusses on how the form represents bleeding puppets, and in doing so, explicates the politics of transmedia performing and viewing. Pili is an example of an anomalous media form that proliferates anomalous media viewing experiences and desires in turn.Beyond a Media Genre: Taiwanese Pili PuppetryConverging the craft technique of puppeteering and digital technology of filmmaking and animation, Pili puppetry creates a new media genre that exceeds any conventional idea of a puppet show or digital puppet, as it is something in-between. Glove puppetry is a popular traditional theatre in Taiwan, often known as “theatre in the palm” because a traditional puppet was roughly the same size as an adult’s palm. The size enabled the puppeteer to easily manipulate a puppet in one hand and be close to the audience. Traditionally, puppet shows occurred to celebrate the local deities’ birthday. Despite its popularity, the form was limited by available technology. For instance, although stories with vigorous battles were particularly popular, bleeding scenes in such an auspicious occasion were inappropriate and rare. As a live theatrical event featuring immediate interaction between the performer and the spectator, realistic bleeding scenes were rare because it is hard to immediately clean the stage during the performance. Distinct from the traditional puppet show, digital puppetry features semi-animated puppets in a virtual world. Digital puppetry is not a new concept by any means in the Western film industry. Animating a 3D puppet is closely associated with motion capture technologies and animation that are manipulated in a digitalised virtual setting (Ferguson). Commonly, the target audience of the Western digital puppetry is children, so educators sometimes use digital puppetry as a pedagogical tool (Potter; Wohlwend). With these young target audience in mind, the producers often avoid violent and bleeding scenes.Pili puppetry differs from digital puppetry in several ways. For instance, instead of targeting a young audience, Pili puppetry consistently extends the traditional martial-arts performance to include bloody fight sequences that enrich the expressiveness of traditional puppetry as a performing art. Moreover, Pili puppetry does not apply the motion capture technologies to manipulate the puppet’s movement, thus retaining the puppeteers’ puppeteering craft (clips of Pili puppetry can be seen on Pili’s official YouTube page). Hence, Pili is a unique hybrid form, creating its own anomalous space in puppetry. Among over a thousand characters across the series, the realistic “human-like” puppet is one of Pili’s most popular selling points. The new media considerably intervene in the puppet design, as close-up shots and high-resolution images can accurately project details of a puppet’s face and body movements on the screen. Consequently, Pili’s puppet modelling becomes increasingly intricate and attractive and arguably makes its virtual figures more epic yet also more “human” (Chen). Figure 1: Su Huan-Jen in the TV series Pili Killing Blade (1993). His facial expressions were relatively flat and rigid then. Reproduced with permission of Pili International Multimedia Company.Figure 2: Su Huan-Jen in the TV series Pili Nine Thrones (2003). The puppet’s facial design and costume became more delicate and complex. Reproduced with permission of Pili International Multimedia Company.Figure 3: Su Huan-Jen in the TV series Pili Fantasy: War of Dragons (2019). His facial lines softened due to more precise design technologies. The new lightweight chiffon yarn costumes made him look more elegant. The multiple-layer costumes also created more space for puppeteers to hide behind the puppet and enact more complicated manipulations. Reproduced with permission of Pili International Multimedia Company.The design of the most well-known Pili swordsman, Su Huan-Jen, demonstrates how the Pili puppet modelling became more refined and intricate in the past 20 years. In 1993, the standard design was a TV puppet with the size and body proportion slightly enlarged from the traditional puppet. Su Huan-Jen’s costumes were made from heavy fabrics, and his facial expressions were relatively flat and rigid (fig. 1). Pili produced its first puppetry film Legend of the Sacred Stone in 2000; considering the visual quality of a big screen, Pili refined the puppet design including replacing wooden eyeballs and plastic hair with real hair and glass eyeballs (Chen). The filmmaking experience inspired Pili to dramatically improve the facial design for all puppets. In 2003, Su’s modelling in Pili Nine Thrones (TV series) became noticeably much more delicate. The puppet’s size was considerably enlarged by almost three times, so a puppeteer had to use two hands to manipulate a puppet. The complex costumes and props made more space for puppeteers to hide behind the puppet and enrich the performance of the fighting movements (fig. 2). In 2019, Su’s new modelling further included new layers of lightweight fabrics, and his makeup and props became more delicate and complex (fig. 3). Such a refined aesthetic design also lends to Pili’s novelty among puppetry performances.Through the transformation of Pili in the context of puppetry history, we see how the handicraft-like puppet itself gradually commercialised into an artistic object that the audience would yearn to collect and project their bodily imagination. Anthropologist Teri Silvio notices that, for some fans, Pili puppets are similar to worship icons through which they project their affection and imaginary identity (Silvio, “Pop Culture Icons”). Intermediating with the new media, the change in the refined puppet design also comes from the audience’s expectations. Pili’s senior puppet designer Fan Shih-Ching mentioned that Pili fans are very involved, so their preferences affect the design of puppets. The complexity, particularly the layer of costumes, most clearly differentiates the aesthetics of traditional and Pili puppets. Due to the “idolisation” of some famous Pili characters, Shih-Ching has had to design more and more gaudy costumes. Each resurgence of a well-known Pili swordsman, such as Su Huan-Jen, Yi Ye Shu, and Ye Hsiao-Chai, means he has to remodel the puppet.Pili fans represent their infatuation for puppet characters through cosplay (literally “costume play”), which is when fans dress up and pretend to be a Pili character. Their cosplay, in particular, reflects the bodily practice of imaginary identity. Silvio observes that most cosplayers choose to dress as characters that are the most visually appealing rather than characters that best suit their body type. They even avoid moving too “naturally” and mainly move from pose-to-pose, similar to the frame-to-frame techne of animation. Thus, we can understand this “cosplay more as reanimating the character using the body as a kind of puppet rather than as an embodied performance of some aspect of self-identity” (Silvio 2019, 167). Hence, Pili fans’ cosplay is indicative of an anomalous desire to become the puppet-like human, which helps them transcend their social roles in their everyday life. It turns out that not only fans’ preference drives the (re)modelling of puppets but also fans attempt to model themselves in the image of their beloved puppets. The reversible dialectic between fan-star and flesh-object further provokes an “anomaly” in terms of the relationship between the viewers and the puppets. Precisely because fans have such an intimate relationship with Pili, it is important to consider how the series’ content and form configure fans’ viewing experience.Filming Bleeding PuppetsDespite its intricate aesthetics, Pili is still a series with frequent fighting-to-the-death scenes, which creates, and is the result of, extraordinary transmedia production and viewing experiences. Due to the market demand of producing episodes around 500 minutes long every month, Pili constantly creates new characters to maintain the audience’s attention and retain its novelty. So far, Pili has released thousands of characters. To ensure that new characters supersede the old ones, numerous old characters have to die within the plot.The adoption of new media allows the fighting scenes in Pili to render as more delicate, rather than consisting of loud, intense action movements. Instead, the leading swordsmen’s death inevitably takes place in a pathetic and romantic setting and consummates with a bloody sacrifice. Fighting scenes in early Pili puppetry created in the late 1980s were still based on puppets’ body movements, as the knowledge and technology of animation were still nascent and underdeveloped. At that time, the prestigious swordsman mainly relied on the fast speed of brandishing his sword. Since the early 1990s, as animation technology matured, it has become very common to see Pili use CGI animation to create a damaging sword beam for puppets to kill target enemies far away. The sword beam can fly much faster than the puppets can move, so almost every fighting scene employs CGI to visualise both sword beams and flame. The change in fighting manners provokes different representations of the bleeding and death scenes. Open wounds replace puncture wounds caused by a traditional weapon; bleeding scenes become typical, and a special feature in Pili’s transmedia puppetry.In addition to CGI animation, the use of fake blood in the Pili studio makes the performance even more realistic. Pili puppet master Ting Chen-Ching recalled that exploded puppets in traditional puppetry were commonly made by styrofoam blocks. The white styrofoam chips that sprayed everywhere after the explosion inevitably made the performance seem less realistic. By contrast, in the Pili studio, the scene of a puppet spurting blood after the explosion usually applies the technology of editing several shots. The typical procedure would be a short take that captures a puppet being injured. In its injury location, puppeteers sprinkle red confetti to represent scattered blood clots in the following shot. Sometimes the fake blood was splashed with the red confetti to make it further three-dimensional (Ting). Bloody scenes can also be filmed through multiple layers of arranged performance conducted at the same time by a group of puppeteers. Ting describes the practice of filming a bleeding puppet. Usually, some puppeteers sprinkle fake blood in front of the camera, while other puppeteers blasted the puppets toward various directions behind the blood to make the visual effects match. If the puppeteers need to show how a puppet becomes injured and vomits blood during the fight, they can install tiny pipes in the puppet in advance. During the filming, the puppeteer slowly squeezes the pipe to make the fake blood flow out from the puppet’s mouth. Such a bloody scene sometimes accompanies tears dropping from the puppet’s eyes. In some cases, the puppeteer drops the blood on the puppet’s mouth prior to the filming and then uses a powerful electric fan to blow the blood drops (Ting). Such techniques direct the blood to flow laterally against the wind, which makes the puppet’s death more aesthetically tragic. Because it is not a live performance, the puppeteer can try repeatedly until the camera captures the most ideal blood drop pattern and bleeding speed. Puppeteers have to adjust the camera distance for different bleeding scenes, which creates new modes of viewing, sensing, and representing virtual life and death. One of the most representative examples of Pili’s bleeding scenes is when Su’s best friend, Ching Yang-Zi, fights with alien devils in Legend of the Sacred Stone. (The clip of how Ching Yang-Zi fights and bleeds to death can be seen on YouTube.) Ting described how Pili prepared three different puppets of Ching for the non-fighting, fighting, and bleeding scenes (Ting). The main fighting scene starts from a low-angle medium shot that shows how Ching Yang-Zi got injured and began bleeding from the corner of his mouth. Then, a sharp weapon flies across the screen; the following close-up shows that the weapon hits Ching and he begins bleeding immediately. The successive shots move back and forth between his face and the wound in medium shot and close-up. Next, a close-up shows him stepping back with blood dripping on the ground. He then pushes the weapon out of his body to defend enemies; a final close-up follows a medium take and a long take shows the massive hemorrhage. The eruption of fluid plasma creates a natural effect that is difficult to achieve, even with 3D animation. Beyond this impressive technicality, the exceptional production and design emphasise how Pili fully embraces the ethos of transmedia: to play with multiple media forms and thereby create a new form. In the case of Pili, its form is interactive, transcending the boundaries of what we might consider the “living” and the “dead”.Epilogue: Viewing Bleeding Puppets on the ScreenThe simulated, high-quality, realistic-looking puppet designs accompanying the Pili’s featured bloody fighting sequence draw another question: What is the effect of watching human-like puppets die? What does this do to viewer-fans? Violence is prevalent throughout the historical record of human behaviour, especially in art and entertainment because these serve as outlets to fulfill a basic human need to indulge in “taboo fantasies” and escape into “realms of forbidden experience” (Schechter). When discussing the visual representations of violence and the spectacle of the sufferings of others, Susan Sontag notes, “if we consider what emotions would be desirable” (102), viewing the pain of others may not simply evoke sympathy. She argues that “[no] moral charge attaches to the representation of these cruelties. Just the provocation: can you look at this? There is the satisfaction of being able to look at the image without flinching. There is the pleasure of flinching” (41). For viewers, the boldness of watching the bloody scenes can be very inviting. Watching human-like puppets die in the action scenes similarly validates the viewer’s need for pleasure and entertainment. Although different from a human body, the puppets still bears the materiality of being-object. Therefore, watching the puppets bleeding and die as distinctly “human-like’ puppets further prevent viewers’ from feeling guilty or morally involved. The conceptual distance of being aware of the puppet’s materiality acts as a moral buffer; audiences are intimately involved through the particular aesthetic arrangement, yet morally detached. The transmedia filming of puppetry adds another layer of mediation over the human-like “living” puppets that allows such a particular experience. Sontag notices that the media generates an inevitable distance between object and subject, between witness and victim. For Sontag, although images constitute “the imaginary proximity” because it makes the “faraway sufferers” be “seen close-up on the television screen”, it is a mystification to assume that images serve as a direct link between sufferers and viewers. Rather, Sontag insists: the distance makes the viewers feel “we are not accomplices to what caused the suffering. Our sympathy proclaims our innocence as well as our impotence” (102). Echoing Sontag’s argument, Jeffrey Goldstein points out that “distancing” oneself from the mayhem represented in media makes it tolerable. Media creates an “almost real” visuality of violence, so the audience feels relatively safe in their surroundings when exposed to threatening images. Thus, “violent imagery must carry cues to its unreality or it loses appeal” (280). Pili puppets that are human-like, thus not human, more easily enable the audience to seek sensational excitement through viewing puppets’ bloody violence and eventual death on the screen and still feel emotionally secure. Due to the distance granted by the medium, viewers gain a sense of power by excitedly viewing the violence with an accompanying sense of moral exemption. Thus, viewers can easily excuse the limits of their personal responsibility while still being captivated by Pili’s boundary-transgressing aesthetic.The anomalous power of Pili fans’ cosplay differentiates the viewing experience of puppets’ deaths from that of other violent entertainment productions. Cosplayers physically bridge viewing/acting and life/death by dressing up as the puppet characters, bringing them to life, as flesh. Cosplay allows fans to compensate for the helplessness they experience when watching the puppets’ deaths on the screen. They can both “enjoy” the innocent pleasure of watching bleeding puppets and bring their adored dead idols “back to life” through cosplay. The onscreen violence and death thus provide an additional layer of pleasure for such cosplayers. They not only take pleasure in watching the puppets—which are an idealized version of their bodily imagination—die, but also feel empowered to revitalise their loved idols. Therefore, Pili cosplayers’ desires incite a cycle of life, pleasure, and death, in which the company responds to their consumers’ demands in kind. The intertwining of social, economic, and political factors thus collectively thrives upon media violence as entertainment. Pili creates the potential for new cross-media genre configurations that transcend the traditional/digital puppetry binary. On the one hand, the design of swordsman puppets become a simulation of a “living object” responding to the camera distance. On the other hand, the fighting and death scenes heavily rely on the puppeteers’ cooperation with animation and editing. Therefore, Pili puppetry enriches existing discourse on both puppetry and animation as life-giving processes. What is animated by Pili puppetry is not simply the swordsmen characters themselves, but new potentials for media genres and violent entertainment. AcknowledgmentMy hearty gratitude to Amy Gaeta for sharing her insights with me on the early stage of this study.ReferencesChen, Jasmine Yu-Hsing. “Transmuting Tradition: The Transformation of Taiwanese Glove Puppetry in Pili Productions.” Journal of the Oriental Society of Australia 51 (2019): 26-46.Ferguson, Jeffrey. “Lessons from Digital Puppetry: Updating a Design Framework for a Perceptual User Interface.” IEEE International Conference on Computer and Information Technology, 2015.Goldstein, Jeffrey. “The Attractions of Violent Entertainment.” Media Psychology 1.3 (1999): 271-282.Potter, Anna. “Funding Contemporary Children’s Television: How Digital Convergence Encourages Retro Reboot.” International Journal on Communications Management 19.2 (2017): 108-112.Schechter, Harold. Savage Pastimes: A Cultural History of Violent Entertainment. 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