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1. Mixed-linker strategy for suppressing structural flexibility of metal-organic framework membranes for gas separation

Author

Chung-Kai Chang, Ting-Rong Ko, Tsai-Yu Lin, Yen-Chun Lin, Hyun Jung Yu, Jong Suk Lee, Yi-Pei Li, Heng-Liang Wu, and Dun-Yen Kang

Subjects
Chemistry, QD1-999
Abstract

Abstract Structural flexibility is a critical issue that limits the application of metal-organic framework (MOF) membranes for gas separation. Herein we propose a mixed-linker approach to suppress the structural flexibility of the CAU-10-based (CAU = Christian-Albrechts-University) membranes. Specifically, pure CAU-10-PDC membranes display high separation performance but at the same time are highly unstable for the separation of CO2/CH4. A partial substitution (30 mol.%) of the linker PDC with BDC significantly improves its stability. Such an approach also allows for decreasing the aperture size of MOFs. The optimized CAU-10-PDC-H (70/30) membrane possesses a high separation performance for CO2/CH4 (separation factor of 74.2 and CO2 permeability of 1,111.1 Barrer under 2 bar of feed pressure at 35°C). A combination of in situ characterization with X-ray diffraction (XRD) and diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, as well as periodic density functional theory (DFT) calculations, unveils the origin of the mixed-linker approach to enhancing the structural stability of the mixed-linker CAU-10-based membranes during the gas permeation tests.

Published
2023
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2. Development of anti-aflatoxin B1 nanobodies from a novel mutagenesis-derived synthetic library for traditional Chinese medicine and foods safety testing

Author

Yu-Ching Lee, Gar-Hwa Lai, Tsai-Yu Lin, Tien-Sheng Tseng, Tsung-Hsun Tsai, Wang-Chuan Chen, Cheng-Chung Lee, and Keng-Chang Tsai

Subjects
Nanobody, Phage display technology, Glove-like cavity, Aflatoxin B1, Nonhypervariable complementarity-determining region 4 loop, Biology (General), QH301-705.5
Abstract

Abstract Background The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay and mass spectrometry. Regarding the development of diagnostic antibody reagents, effective methods for the rapid preparation of specific monoclonal antibodies are inadequate. Methods In this study, a novel synthetic phage-displayed nanobody Golden Glove (SynaGG) library with a glove-like cavity configuration was established using phage display technology in synthetic biology. We applied this unique SynaGG library on the small molecule aflatoxin B1 (AFB1), which has strong hepatotoxicity, to isolate specific nanobodies with high affinity for AFB1. Result These nanobodies exhibit no cross-reactivity with the hapten methotrexate, which is recognized by the original antibody template. By binding to AFB1, two nanobodies can neutralize AFB1-induced hepatocyte growth inhibition. Using molecular docking, we found that the unique non-hypervariable complementarity-determining region 4 (CDR4) loop region of the nanobody was involved in the interaction with AFB1. Specifically, the CDR4’s positively charged amino acid arginine directed the binding interaction between the nanobody and AFB1. We then rationally optimized the interaction between AFB1 and the nanobody by mutating serine at position 2 into valine. The binding affinity of the nanobody to AFB1 was effectively improved, and this result supported the use of molecular structure simulation for antibody optimization. Conclusion In summary, this study revealed that the novel SynaGG library, which was constructed through computer-aided design, can be used to isolate nanobodies that specifically bind to small molecules. The results of this study could facilitate the development of nanobody materials to detect small molecules for the rapid screening of TCM materials and foods in the future.

Published
2023
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3. Meeting FDA Guidance recommendations for replication-competent virus and insertional oncogenesis testing

Author

Kenneth Cornetta, Tsai-Yu Lin, Danilo Pellin, and Donald B. Kohn

Subjects
replication-competent retrovirus, insertional oncogenesis, gene therapy, safety, FDA regulations, Genetics, QH426-470, Cytology, QH573-671
Abstract

Integrating vectors are associated with alterations in cellular function related to disruption of normal gene function. This has been associated with clonal expansion of cells and, in some instances, cancer. These events have been associated with replication-defective vectors and suggest that the inadvertent exposure to a replication-competent virus arising during vector manufacture would significantly increase the risk of treatment-related adverse events. These risks have led regulatory agencies to require specific monitoring for replication-competent viruses, both prior to and after treatment of patients with gene therapy products. Monitoring the risk of cell expansion and malignancy is also required. In this review, we discuss the rational potential approaches and challenges to meeting the US FDA expectations listed in current guidance documents.

Published
2023
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4. Blockade effect of avian-derived anti-VISTA antibodies on immunosuppressive responses

Author

Yun-Shih Lin, Shang-Ju Hsieh, Keng-Chang Tsai, Ming-Hui Cheng, Tz-Wen Yang, Tsai-Yu Lin, Fu-Ling Chang, Chen-Wei Chiang, Wang-Chuan Chen, Hsien-Te Huang, and Yu-Ching Lee

Subjects
vista, phage display technique, single-chain variable fragments, molecular docking, immune checkpoints, Biotechnology, TP248.13-248.65, Life, QH501-531
Abstract

B7 family members and their receptors have been confirmed to participate in T cell response signaling through the induction of immunosuppressive effects. The V-domain Ig suppressor of T-cell activation (VISTA) is expressed in myeloid cells as well as T lymphocytes and plays a crucial role in immune responses. In this study, the phage display technique was employed to isolate specific antibodies targeting VISTA in chickens. In in vitro experiments, VISTA could trigger the inhibition of T-cell activation through interaction during binding. However, isolated single-chain variable fragments (scFvs) effectively inhibited immune cells from producing exhaustion responses, freeing the T cells in peripheral blood mononuclear cells from inhibition and allowing them to remain activated. In addition, the isolated scFvs can block the interaction between VISTA and the VSIG3 ligand. Further analysis on one scFv VS10 revealed that a significant insertion mutation occurred at the CDR3 of the VH domain compared to the chicken germline sequence. Finally, the complex structures of scFv VS10 and VISTA were simulated using molecular docking, and the interaction produced was analyzed. The experimental results support the applicability of VISTA as a target for immune checkpoints and contribute to explaining geometric structures and properties in chicken antibodies.

Published
2022
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5. Effectiveness of anti-erythropoietin producing Hepatocellular receptor Type-A2 antibody in pancreatic cancer treatment

Author

Fu-Ling Chang, Keng-Chang Tsai, Tsai-Yu Lin, Chen-Wei Chiang, Shiow-Lin Pan, and Yu-Ching Lee

Subjects
Erythropoietin-producing hepatocyte receptor type-A2, Pancreatic cancer, Phage display, EphA2 degradation, Improved effects, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Erythropoietin-producing hepatocyte receptor type A2 (EphA2) is a tyrosine kinase that binds to ephrins (e.g., ephrin-A1) to initiate bidirectional signaling between cells. The binding of EphA2 and ephrin-A1 leads to the inhibition of Ras-MAPK activity and tumor growth. During tumorigenesis, the normal interaction between EphA2 and ephrin-A1 is hindered, which leads to the overexpression of EphA2 and induces cancer. The overexpression of EphA2 has been identified as a notable tumor marker in diagnosing and treating pancreatic cancer. In this study, we used phage display to isolate specific antibodies against the active site of EphA2 by using a discontinuous recombinant epitope for immunization. The therapeutic efficacy and inhibition mechanism of the generated antibody against pancreatic cancer was validated and clarified. The generated antibodies were bound to the conformational epitope of endogenous EphA2 on cancer cells, thus inducing cellular endocytosis and causing EphA2 degradation. Molecule signals pAKT, pERK, pFAK, and pSTAT3 were weakened, inhibiting the proliferation and migration of pancreatic cancer cells. The humanized antibody hSD5 could effectively inhibit the growth of the xenograft pancreatic cancer tumor cells BxPc-3 and Mia PaCa-2 in mice, respectively. When antibody hSD5 was administered with gemcitabine, significantly improved effects on tumor growth inhibition were observed. Based on the efficacy of the IgG hSD5 antibodies, clinical administration of the hSD5 antibodies is likely to suppress tumors in patients with pancreatic cancer and abnormal activation or overexpression of EphA2 signaling.

Published
2023
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6. BADTV: Unveiling Backdoor Threats in Third-Party Task Vectors

Author

Hsu, Chia-Yi, Tsai, Yu-Lin, Zhe, Yu, Chen, Yan-Lun, Lin, Chih-Hsun, Yu, Chia-Mu, Zhang, Yang, Huang, Chun-Ying, and Sakuma, Jun

Subjects
Computer Science - Machine Learning, Computer Science - Cryptography and Security
Abstract

Task arithmetic in large-scale pre-trained models enables flexible adaptation to diverse downstream tasks without extensive re-training. By leveraging task vectors (TVs), users can perform modular updates to pre-trained models through simple arithmetic operations like addition and subtraction. However, this flexibility introduces new security vulnerabilities. In this paper, we identify and evaluate the susceptibility of TVs to backdoor attacks, demonstrating how malicious actors can exploit TVs to compromise model integrity. By developing composite backdoors and eliminating redudant clean tasks, we introduce BadTV, a novel backdoor attack specifically designed to remain effective under task learning, forgetting, and analogies operations. Our extensive experiments reveal that BadTV achieves near-perfect attack success rates across various scenarios, significantly impacting the security of models using task arithmetic. We also explore existing defenses, showing that current methods fail to detect or mitigate BadTV. Our findings highlight the need for robust defense mechanisms to secure TVs in real-world applications, especially as TV services become more popular in machine-learning ecosystems.

Published
2025

7. Differentially Private Fine-Tuning of Diffusion Models

Author

Tsai, Yu-Lin, Li, Yizhe, Chen, Zekai, Chen, Po-Yu, Yu, Chia-Mu, Ren, Xuebin, and Buet-Golfouse, Francois

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence, Computer Science - Cryptography and Security
Abstract

The integration of Differential Privacy (DP) with diffusion models (DMs) presents a promising yet challenging frontier, particularly due to the substantial memorization capabilities of DMs that pose significant privacy risks. Differential privacy offers a rigorous framework for safeguarding individual data points during model training, with Differential Privacy Stochastic Gradient Descent (DP-SGD) being a prominent implementation. Diffusion method decomposes image generation into iterative steps, theoretically aligning well with DP's incremental noise addition. Despite the natural fit, the unique architecture of DMs necessitates tailored approaches to effectively balance privacy-utility trade-off. Recent developments in this field have highlighted the potential for generating high-quality synthetic data by pre-training on public data (i.e., ImageNet) and fine-tuning on private data, however, there is a pronounced gap in research on optimizing the trade-offs involved in DP settings, particularly concerning parameter efficiency and model scalability. Our work addresses this by proposing a parameter-efficient fine-tuning strategy optimized for private diffusion models, which minimizes the number of trainable parameters to enhance the privacy-utility trade-off. We empirically demonstrate that our method achieves state-of-the-art performance in DP synthesis, significantly surpassing previous benchmarks on widely studied datasets (e.g., with only 0.47M trainable parameters, achieving a more than 35% improvement over the previous state-of-the-art with a small privacy budget on the CelebA-64 dataset). Anonymous codes available at https://anonymous.4open.science/r/DP-LORA-F02F., Comment: 16 pages, 5 figures, 11 tables

Published
2024

8. Safe LoRA: the Silver Lining of Reducing Safety Risks when Fine-tuning Large Language Models

Author

Hsu, Chia-Yi, Tsai, Yu-Lin, Lin, Chih-Hsun, Chen, Pin-Yu, Yu, Chia-Mu, and Huang, Chun-Ying

Subjects
Computer Science - Machine Learning
Abstract

While large language models (LLMs) such as Llama-2 or GPT-4 have shown impressive zero-shot performance, fine-tuning is still necessary to enhance their performance for customized datasets, domain-specific tasks, or other private needs. However, fine-tuning all parameters of LLMs requires significant hardware resources, which can be impractical for typical users. Therefore, parameter-efficient fine-tuning such as LoRA have emerged, allowing users to fine-tune LLMs without the need for considerable computing resources, with little performance degradation compared to fine-tuning all parameters. Unfortunately, recent studies indicate that fine-tuning can increase the risk to the safety of LLMs, even when data does not contain malicious content. To address this challenge, we propose Safe LoRA, a simple one-liner patch to the original LoRA implementation by introducing the projection of LoRA weights from selected layers to the safety-aligned subspace, effectively reducing the safety risks in LLM fine-tuning while maintaining utility. It is worth noting that Safe LoRA is a training-free and data-free approach, as it only requires the knowledge of the weights from the base and aligned LLMs. Our extensive experiments demonstrate that when fine-tuning on purely malicious data, Safe LoRA retains similar safety performance as the original aligned model. Moreover, when the fine-tuning dataset contains a mixture of both benign and malicious data, Safe LoRA mitigates the negative effect made by malicious data while preserving performance on downstream tasks. Our codes are available at \url{https://github.com/IBM/SafeLoRA}., Comment: This is the camera-ready version accepted for NeurIPS 2024

Published
2024

10. Ring-A-Bell! How Reliable are Concept Removal Methods for Diffusion Models?

Author

Tsai, Yu-Lin, Hsu, Chia-Yi, Xie, Chulin, Lin, Chih-Hsun, Chen, Jia-You, Li, Bo, Chen, Pin-Yu, Yu, Chia-Mu, and Huang, Chun-Ying

Subjects
Computer Science - Machine Learning
Abstract

Diffusion models for text-to-image (T2I) synthesis, such as Stable Diffusion (SD), have recently demonstrated exceptional capabilities for generating high-quality content. However, this progress has raised several concerns of potential misuse, particularly in creating copyrighted, prohibited, and restricted content, or NSFW (not safe for work) images. While efforts have been made to mitigate such problems, either by implementing a safety filter at the evaluation stage or by fine-tuning models to eliminate undesirable concepts or styles, the effectiveness of these safety measures in dealing with a wide range of prompts remains largely unexplored. In this work, we aim to investigate these safety mechanisms by proposing one novel concept retrieval algorithm for evaluation. We introduce Ring-A-Bell, a model-agnostic red-teaming tool for T2I diffusion models, where the whole evaluation can be prepared in advance without prior knowledge of the target model. Specifically, Ring-A-Bell first performs concept extraction to obtain holistic representations for sensitive and inappropriate concepts. Subsequently, by leveraging the extracted concept, Ring-A-Bell automatically identifies problematic prompts for diffusion models with the corresponding generation of inappropriate content, allowing the user to assess the reliability of deployed safety mechanisms. Finally, we empirically validate our method by testing online services such as Midjourney and various methods of concept removal. Our results show that Ring-A-Bell, by manipulating safe prompting benchmarks, can transform prompts that were originally regarded as safe to evade existing safety mechanisms, thus revealing the defects of the so-called safety mechanisms which could practically lead to the generation of harmful contents. Our codes are available at https://github.com/chiayi-hsu/Ring-A-Bell., Comment: This paper has already been accepted by ICLR 2024. This version is the camera-ready version

Published
2023

11. Exploring the Benefits of Visual Prompting in Differential Privacy

Author

Li, Yizhe, Tsai, Yu-Lin, Ren, Xuebin, Yu, Chia-Mu, and Chen, Pin-Yu

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Cryptography and Security, Computer Science - Machine Learning
Abstract

Visual Prompting (VP) is an emerging and powerful technique that allows sample-efficient adaptation to downstream tasks by engineering a well-trained frozen source model. In this work, we explore the benefits of VP in constructing compelling neural network classifiers with differential privacy (DP). We explore and integrate VP into canonical DP training methods and demonstrate its simplicity and efficiency. In particular, we discover that VP in tandem with PATE, a state-of-the-art DP training method that leverages the knowledge transfer from an ensemble of teachers, achieves the state-of-the-art privacy-utility trade-off with minimum expenditure of privacy budget. Moreover, we conduct additional experiments on cross-domain image classification with a sufficient domain gap to further unveil the advantage of VP in DP. Lastly, we also conduct extensive ablation studies to validate the effectiveness and contribution of VP under DP consideration. Our code is available at (https://github.com/EzzzLi/Prompt-PATE)., Comment: Published at ICCV 2023

Published
2023

12. Certified Robustness of Quantum Classifiers against Adversarial Examples through Quantum Noise

Author

Huang, Jhih-Cing, Tsai, Yu-Lin, Yang, Chao-Han Huck, Su, Cheng-Fang, Yu, Chia-Mu, Chen, Pin-Yu, and Kuo, Sy-Yen

Subjects
Quantum Physics, Computer Science - Machine Learning, Computer Science - Neural and Evolutionary Computing, Electrical Engineering and Systems Science - Signal Processing
Abstract

Recently, quantum classifiers have been found to be vulnerable to adversarial attacks, in which quantum classifiers are deceived by imperceptible noises, leading to misclassification. In this paper, we propose the first theoretical study demonstrating that adding quantum random rotation noise can improve robustness in quantum classifiers against adversarial attacks. We link the definition of differential privacy and show that the quantum classifier trained with the natural presence of additive noise is differentially private. Finally, we derive a certified robustness bound to enable quantum classifiers to defend against adversarial examples, supported by experimental results simulated with noises from IBM's 7-qubits device., Comment: Accepted to IEEE ICASSP 2023

Published
2022

18. Low Bone Mineral Density as a Predictor of Mortality and Infections in Stroke Patients: A Hospital-Based Study.

Author

Tsai, Yu-Lin, Chuang, Ya-Chi, Cheng, Yuan-Yang, Deng, Ya-Lian, Lin, Shih-Yi, and Hsu, Chun-Sheng

Subjects
URINARY tract infections, DISEASE risk factors, STROKE patients, PNEUMONIA-related mortality, LOG-rank test, BONE density
Abstract

Context Low bone mineral density (BMD) has been linked to elevated risks of mortality and infections in the general population; however, its association with these outcomes in stroke patients remains unclear. Objective This study aims to investigate the correlation between low BMD and risks of mortality and infections among stroke patients in a Taiwanese cohort. Methods In this single-center retrospective cohort study, 905 stroke patients from a Taiwanese database (2000-2022) were analyzed. Patients were grouped based on BMD measurements of the femur and spine. The primary outcome was all-cause mortality, and secondary outcomes included urinary tract infection (UTI) and pneumonia. Accelerated failure time regression model analyses evaluated the association between BMD and these outcomes, while the Kaplan-Meier method and log-rank test assessed survival differences between groups. Results Among the participants (average age 76.1 years, 70.5% female), 33.82% had osteopenia and 55.25% had osteoporosis. Stroke patients with lower spine and right femur BMD had significantly reduced survival rates, especially when the BMD value fell below 0.842 g/cm2 (spine), and 0.624 g/cm2 (right femur), respectively. Regarding secondary outcomes, lower spine BMD was significantly associated with an increased risk of UTI. Conclusion Low BMD, particularly in the femur and spine, is a significant predictor of mortality and UTI in stroke patients. These findings highlight the importance of assessing and managing BMD in stroke patients to improve outcomes and reduce complications. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials

Author

Kenneth Cornetta, Jing Yao, Kimberley House, Lisa Duffy, Prasad S. Adusumilli, Rachel Beyer, Claire Booth, Malcolm Brenner, Kevin Curran, Bambi Grilley, Helen Heslop, Christian S. Hinrichs, Rosandra N. Kaplan, Hans-Peter Kiem, James Kochenderfer, Donald B. Kohn, Sham Mailankody, Scott M. Norberg, Roisin E. O'Cearbhaill, Jennifer Pappas, Jae Park, Carlos Ramos, Antonio Ribas, Isabelle Rivière, Steven A. Rosenberg, Craig Sauter, Nirali N. Shah, Susan F. Slovin, Adrian Thrasher, David A. Williams, and Tsai-Yu Lin

Subjects
Pharmacology, Drug Discovery, Genetics, Molecular Medicine, Molecular Biology
Abstract

The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy.

Published
2023
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26. Effects of Complete Oral Motor Intervention and Nonnutritive Sucking Alone on the Feeding Performance of Premature Infants: A Systematic Review and Meta-Analysis.

Author

Tsai, Yu-Lin, Hsieh, Pei-Chun, Chen, Ting-Yen, and Lin, Yu-Ching

Subjects
MEDICAL databases, LENGTH of stay in hospitals, META-analysis, MEDICAL information storage & retrieval systems, CONFIDENCE intervals, SYSTEMATIC reviews, TRANSITIONAL care, ORAL habits, INFANT nutrition, WEIGHT gain, COMPARATIVE studies, QUALITY assurance, STATISTICAL hypothesis testing, MEDLINE, SENSITIVITY & specificity (Statistics), MOTOR ability, CHILDREN
Abstract

We explore the effect of complete oral motor intervention (OMI) and nonnutritive sucking (NNS) alone on oral feeding in preterm infants through a meta-analysis. We searched the Embased, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials up to 8 August 2023, based on established selection criteria. Quality evaluations of the studies were carried out by applying both the Cochrane risk of bias assessment tool and the Jadad scale. The outcome measures of three clinical indicators included transition time to oral feeding, weight gain, and hospitalization duration. We conducted a meta-analysis using a random-effects model to determine the pooled effect sizes, expressed as standardized mean differences (SMDs) and their corresponding confidence intervals (CIs). Additionally, we undertook a subgroup analysis and meta-regression to investigate any potential moderating factors. Eight randomized controlled trials with 419 participants were selected. Meta-analysis revealed that receiving a complete OMI had significantly reduced transition time compared with those receiving NNS alone in preterm newborns (SMD, −1.186; 95% CI, −2.160 to −0.212, p = 0.017). However, complete OMI had no significant effect on shortened hospitalization duration (SMD, −0.394; 95% CI, −0.979 to 0.192, p = 0.188) and increased weight gain (SMD, 0.346; 95% CI, −0.147 to 0.838, p = 0.169) compared with NNS alone. In brief, a complete OMI should not be replaced by NNS alone. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed randomized controlled trials are necessary to confirm our conclusion. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Mixed-linker strategy for suppressing structural flexibility of MOF membranes for gas separation

Author

Chung-Kai Chang, Ting-Rong Ko, Tsai-Yu Lin, Yen-Chun Lin, Hyun Jung Yu, Jong Suk Lee, Yi-Pei Li, Heng-Liang Wu, and Dun-Yen Kang

Abstract

Structural flexibility is a critical issue that limits the applications of MOF membranes for gas separation. Herein we propose a mixed-linker approach to suppress the structural flexibility of the CAU-10-based membranes. Specifically, pure CAU-10-PDC membrane is of high separation performance but at the same time highly unstable for the separation of CO2/CH4. A partial substitution (30 mol.%) of the linker PDC with BDC significantly improves its stability. Such an approach also allows for the aperture size of MOFs. The optimized CAU-10-PDC-H (70/30) membrane possesses a high separation performance for CO2/CH4 (separation factor of 76 and CO2 permeability of 1,111 Barrer under 2 bar of feed pressure at 35 ℃). A combination of in situ characterization with XRD and DRIFT spectroscopy, as well as DFT calculations, unveils the origin of the mixed-linker approach to enhancing the structural stability of the mixed-linker CAU-10-based membranes during the gas permeation tests.

Published
2023
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32. Effectiveness of Anti-Erythropoietin Producing Hepatocellular Receptor Type-A2 Antibody in Pancreatic Cancer Treatment

Author

Fu-Ling Chang, Keng-Chang Tsai, Tsai-Yu Lin, Chen-Wei Chiang, Wang-Chuan Chen, Shiow-Lin Pan, and Yu-Ching Lee

Abstract

Background Related to the pathogenesis of cancers in humans, the interaction between erythropoietin-producing hepatocyte receptors and ephrins (Ephs/ephrins) affects and regulates various biological functions. Erythropoietin-producing hepatocyte receptor type A2 (EphA2) is a tyrosine kinase that binds to ephrins (e.g., ephrin-A1) to initiate bidirectional signaling between cells. The binding of EphA2 and ephrin-A1 leads to the inhibition of Ras-MAPK activity and tumor growth. During tumorigenesis, the normal interaction between EphA2 and ephrin-A1 is hindered, which leads to the overexpression of EphA2 and induces cancer. The overexpression of EphA2 has been identified as a notable tumor marker in the diagnosis and treatment of pancreatic cancer. Results In this study, we used phage display to isolate specific antibodies against the active site of EphA2 molecules by using a discontinuous recombinant epitope for immunization. The therapeutic efficacy and inhibition mechanism of the generated antibody against pancreatic cancer was validated and clarified. The generated antibodies were bound to the conformational epitope of endogenous EphA2 on cancer cells, thus inducing cellular endocytosis and causing EphA2 degradation. Molecule signals pAKT, pERK, pFAK, and pSTAT3 were weakened, thereby inhibiting the proliferation and migration of pancreatic cancer cells. The humanized antibody hSD5 could effectively inhibit the growth of the xenograft pancreatic cancer tumor cells BxPc-3 and Mia PaCa-2 in mice, respectively. When antibody hSD5 was administered in combination with gemcitabine, significantly synergistic effects on tumor growth inhibition (reach 79.3%) were observed. Conclusions On the basis of the efficacy of the IgG hSD5 antibody, clinical administration of the hSD5 antibody is likely to suppress tumors in patients with pancreatic cancer and abnormal activation or overexpression of EphA2 signaling.

Published
2022
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33. A Literature Review of Patient-related Risk Factors for Late Implant Failure

Author

Shih-Hsuan Tsai, Shih-Hsuan Tsai, primary, Shih-Hsuan Tsai, Yu-Lin Lai, additional, Yu-Lin Lai, Yi-Chun Lin, additional, Yi-Chun Lin, Hsuan-Hung Chen, additional, Hsuan-Hung Chen, Shan-Ling Hung, additional, Shan-Ling Hung, Ching-Yi Wu, additional, Ching-Yi Wu, Chien-hsin Wang, additional, and Chien-hsin Wang, Ya-Chi Chen, additional

Published
2022
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34. The Application of Soft Robotic Gloves in Stroke Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Author

Ko, Ming-Jian, Chuang, Ya-Chi, Ou-Yang, Liang-Jun, Cheng, Yuan-Yang, Tsai, Yu-Lin, and Lee, Yu-Chun

Subjects
SOFT robotics, RANDOMIZED controlled trials, STROKE patients, SOFT contact lenses, BIBLIOGRAPHIC databases, FORELIMB, SURGICAL gloves
Abstract

Wearable robotic devices have been strongly put into use in both the clinical and research fields of stroke rehabilitation over the past decades. This study aimed to explore the effectiveness of soft robotic gloves (SRGs) towards improving the motor recovery and functional abilities in patients with post-stroke hemiparesis. Five major bibliographic databases, PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database, were all reviewed for enrollment regarding comparative trials prior to 7 March 2023. We included adults with stroke and compared their rehabilitation using SRGs to conventional rehabilitation (CR) on hand function in terms of the Fugl-Meyer Upper Extremity Motor Assessment (FMA-UE), Fugl-Meyer Distal Upper Extremity Motor Assessment (FMA-distal UE), box and blocks test score, grip strength test, and the Jebsen–Taylor hand function test (JTT). A total of 8 studies, comprising 309 participants, were included in the analysis. Compared to CR, rehabilitation involving SRGs achieved better FMA-UE (MD 6.52, 95% CI: 3.65~9.39), FMA-distal UE (MD 3.27, 95% CI: 1.50~5.04), and JJT (MD 13.34, CI: 5.16~21.53) results. Subgroup analysis showed that stroke latency of more than 6 months and training for more than 30 min offered a better effect as well. In conclusion, for patients with stroke, rehabilitation using SRGs is recommended to promote the functional abilities of the upper extremities. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Abnormal Two-Stage Degradation on P-Type Low-Temperature Polycrystalline-Silicon Thin-Film Transistor Under Hot Carrier Conditions

Author

Tu, Hong-Yi, primary, Chang, Ting-Chang, additional, Tsao, Yu-Ching, additional, Tai, Mao-Chou, additional, Zheng, Yu-Zhe, additional, Tu, Yu-Fa, additional, Kuo, Chuan-Wei, additional, Wu, Chia-Chuan, additional, Tsai, Yu-Lin, additional, Tsai, Tsung-Ming, additional, Lin, Chih-Chih, additional, and Chien, Ya-Ting, additional

Published
2022
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44. Boosting photocatalytic CO2 reduction in a ZnS/ZnIn2S4 heterostructure through strain-induced direct Z-scheme and a mechanistic study of molecular CO2 interaction thereon

Author

Amr Sabbah, Indrajit Shown, Mohammad Qorbani, Fang-Yu Fu, Tsai-Yu Lin, Heng-Liang Wu, Po-Wen Chung, Chih-I. Wu, Svette Reina Merden Santiago, Ji-Lin Shen, Kuei-Hsien Chen, and Li-Chyong Chen

Subjects
Renewable Energy, Sustainability and the Environment, General Materials Science, Electrical and Electronic Engineering
Published
2022
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45. Metal-free four-in-one modification of g-C3N4 for superior photocatalytic CO2 reduction and H2 evolution

Author

Shaham Quadir, Kuei-Hsien Chen, Mohamed Hammad Elsayed, Heng-Liang Wu, Tsai Yu Lin, Po-Wen Chung, Amr Sabbah, Li-Chyong Chen, Mahmoud Kamal Hussien, Der-Lii M. Tzou, Ming-Chang Lin, Ho-Hsiu Chou, Putikam Raghunath, Mohammad Qorbani, and Hong-Yi Wang

Subjects
Thermal oxidation, Materials science, Nanoporous, General Chemical Engineering, Quantum yield, General Chemistry, Industrial and Manufacturing Engineering, Adsorption, Chemical engineering, Specific surface area, Photocatalysis, Environmental Chemistry, Surface modification, Hydrogen production
Abstract

Utilization of g-C3N4 as a single photocatalyst material without combination with other semiconductor remains challenging. Herein, we report a facile green method for synthesizing a metal free modified g-C3N4 photocatalyst. The modification process combines four different strategies in a one-pot thermal reaction: non-metal doping, porosity generation, functionalization with amino groups, and thermal oxidation etching. The as-prepared amino-functionalized ultrathin nanoporous boron-doped g-C3N4 exhibited a high specific surface area of 143.2 m2 g−1 which resulted in abundant adsorption sites for CO2 and water molecules. The surface amino groups act as Lewis basic sites to adsorb acidic CO2 molecules, which can also serve as active sites to facilitate hydrogen generation. Besides, the simultaneous use of ammonium chloride as a dynamic gas bubble template along with thermal oxidation etching efficiently boosts the delamination of the g-C3N4 layers to produce ultrathin sheets; this leads to stronger light–matter interactions and efficient charge generation. Consequently, the newly modified g-C3N4 achieved selective gas-phase CO2 reduction into CO with a production yield of 21.95 µmol g−1, in the absence of any cocatalyst. Moreover, a high hydrogen generation rate of 3800 µmol g-1h−1 and prominent apparent quantum yield of 10.6% were recorded. This work opens up a new avenue to explore different rational modifications of g-C3N4 nanosheets for the efficient production of clean energy.

Published
2022
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47. Nickel-Catalyzed Denitrogenative Cyclization of 1,2,3,4-Benzothiatriazin-1,1(2 H )-dioxides with Arynes To Synthesize Biaryl Sultams.

Author

Thorat VH, Tsai YL, Huang YR, Cheng CH, and Hsieh JC

Subjects
Catalysis, Cyclization, Naphthalenesulfonates, Stereoisomerism, Nickel
Abstract

Herein, we report the nickel-catalyzed denitrogenative cyclization reaction of 1,2,3,4-benzothiatriazine-1,1-dioxides with arynes to generate the polysubstituted biaryl sultams with tolerance of a wide diversity of substituents on every subunit. The mechanistic study indicates that the reaction is initiated by the formation of a diradical species, which reacts with a nickel complex to form a nickelacycle intermediate and carries out the subsequent cyclization through insertion of an aryne.

Published
2022
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