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Article ; Online: Adipose stem cells preincubated with theanine exert liver regeneration through increase of stem cell paracrine VEGF and suppression of ROS, pyroptosis as well as autophagy markers in liver damage induced by N-nitrosodiethylamine.

Chen, Tung-Sheng / Lai, Yi-An / Lai, Yun-Ju / Chien, Chiang-Ting

2022 Volume 308, Page(s) 120969

Abstract: Aims: Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell ... ...

Abstract	Aims: Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. This study investigates if protective effect on the liver by stem cells preincubated with theanine is better than that from stem cells without preincubated theanine. Methods: We transplanted theanine preincubated adipose-derived stem cells (ADSC) to male Wistar rats with liver dysfunction induced by N-nitrosodiethylamine. The viability, migration and antioxidant capabilities were performed in the ADSC pre-incubated with theanine. Hepatic functional, structural and molecular assays were determined in the animals with or without theanine preincubated ADSC. Key findings: Cell model revealed that ADSC preincubated with green tea theanine (T-ADSC) increased cell capabilities including viability, migration and paracrine secretion. In vivo results indicated that several pathological conditions were observed in rats with liver injury induced by DEN including structural changes and expression of pyroptosis as well as autophagy markers. The above pathological conditions were improved when the rats received both ADSC and T-ADSC treatment. Furthermore, T-ADSC showed better therapeutic effect on rats with liver injury than ADSC due to significant suppression of pyroptosis markers caspase-1 and IL-1β as well as autophagy marker LC3-II accompanied with intensive paracrine VEGF from T-ADSC. Significance: Increased paracrine VEGF secretion from T-ADSC plays a crucial role in liver regeneration. A future clinical study may be designed for further verification of these experimental in vivo findings.
MeSH term(s)	Adipose Tissue/metabolism ; Animals ; Antioxidants/pharmacology ; Autophagy ; Biomarkers/metabolism ; Caspases/metabolism ; Diethylnitrosamine/toxicity ; Glutamates/pharmacology ; Liver Diseases/metabolism ; Liver Regeneration ; Male ; Pyroptosis ; Quality of Life ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Stem Cells/metabolism ; Tea ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Antioxidants ; Biomarkers ; Glutamates ; Reactive Oxygen Species ; Tea ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Diethylnitrosamine (3IQ78TTX1A) ; theanine (8021PR16QO) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2022-09-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120969
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Article: Fabrication of nanocrystal forms of ᴅ-cycloserine and their application for transdermal and enteric drug delivery systems.

Tsai, Hsuan-Ang / Shih, Tsai-Miao / Tsai, Theodore / Hu, Jhe-Wei / Lai, Yi-An / Hsiao, Jui-Fu / Tsai, Guochuan Emil

Beilstein journal of nanotechnology

2024 Volume 15, Page(s) 465–474

Abstract: ᴅ-cycloserine (DCS), an FDA-approved medicine for the treatment of tuberculosis, is also a partial agonist at the glycine recognition site ... ...

Abstract	ᴅ-cycloserine (DCS), an FDA-approved medicine for the treatment of tuberculosis, is also a partial agonist at the glycine recognition site of
Language	English
Publishing date	2024-04-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2583584-1
ISSN	2190-4286
ISSN	2190-4286
DOI	10.3762/bjnano.15.42
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Book ; Online: Improving Prediction Backward-Compatiblility in NLP Model Upgrade with Gated Fusion

Lai, Yi-An / Mansimov, Elman / Xie, Yuqing / Zhang, Yi

2023

Abstract: When upgrading neural models to a newer version, new errors that were not encountered in the legacy version can be introduced, known as regression errors. This inconsistent behavior during model upgrade often outweighs the benefits of accuracy gain and ... ...

Abstract	When upgrading neural models to a newer version, new errors that were not encountered in the legacy version can be introduced, known as regression errors. This inconsistent behavior during model upgrade often outweighs the benefits of accuracy gain and hinders the adoption of new models. To mitigate regression errors from model upgrade, distillation and ensemble have proven to be viable solutions without significant compromise in performance. Despite the progress, these approaches attained an incremental reduction in regression which is still far from achieving backward-compatible model upgrade. In this work, we propose a novel method, Gated Fusion, that promotes backward compatibility via learning to mix predictions between old and new models. Empirical results on two distinct model upgrade scenarios show that our method reduces the number of regression errors by 62% on average, outperforming the strongest baseline by an average of 25%. Comment: Camera-ready for EACL 2023 Findings
Keywords	Computer Science - Computation and Language
Publishing date	2023-02-03
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Adipose stem cells preincubated with theanine exert liver regeneration through increase of stem cell paracrine VEGF and suppression of ROS, pyroptosis as well as autophagy markers in liver damage induced by N-nitrosodiethylamine

Chen, Tung-Sheng / Lai, Yi-An / Lai, Yun-Ju / Chien, Chiang-Ting

Life sciences. 2022 Nov. 01, v. 308

2022

Abstract: Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. ... ...

Abstract	Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. This study investigates if protective effect on the liver by stem cells preincubated with theanine is better than that from stem cells without preincubated theanine. We transplanted theanine preincubated adipose-derived stem cells (ADSC) to male Wistar rats with liver dysfunction induced by N-nitrosodiethylamine. The viability, migration and antioxidant capabilities were performed in the ADSC pre-incubated with theanine. Hepatic functional, structural and molecular assays were determined in the animals with or without theanine preincubated ADSC. Cell model revealed that ADSC preincubated with green tea theanine (T-ADSC) increased cell capabilities including viability, migration and paracrine secretion. In vivo results indicated that several pathological conditions were observed in rats with liver injury induced by DEN including structural changes and expression of pyroptosis as well as autophagy markers. The above pathological conditions were improved when the rats received both ADSC and T-ADSC treatment. Furthermore, T-ADSC showed better therapeutic effect on rats with liver injury than ADSC due to significant suppression of pyroptosis markers caspase-1 and IL-1β as well as autophagy marker LC3-II accompanied with intensive paracrine VEGF from T-ADSC. Increased paracrine VEGF secretion from T-ADSC plays a crucial role in liver regeneration. A future clinical study may be designed for further verification of these experimental in vivo findings.
Keywords	amino acids ; antioxidants ; autophagy ; caspase-1 ; diethylnitrosamine ; green tea ; liver ; liver regeneration ; males ; models ; protective effect ; pyroptosis ; quality of life ; secretion ; stem cells ; theanine ; therapeutics ; viability
Language	English
Dates of publication	2022-1101
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120969
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Global epidemiology of vaccine-derived poliovirus 2016-2021: A descriptive analysis and retrospective case-control study.

Lai, Yi An / Chen, Xin / Kunasekaran, Mohana / Rahman, Bayzidur / MacIntyre, Chandini Raina

EClinicalMedicine

2022 Volume 50, Page(s) 101508

Abstract: Background: Vaccine derived poliovirus (VDPV) remains a major barrier to polio eradication, and recent growing emergences are concerning. This paper presents the global epidemiology of circulating VDPV (cVDPV) by exploring associations between ... ...

Abstract	Background: Vaccine derived poliovirus (VDPV) remains a major barrier to polio eradication, and recent growing emergences are concerning. This paper presents the global epidemiology of circulating VDPV (cVDPV) by exploring associations between demographic and socioeconomic factors with its recent rise. Methods: Data on reported cVDPV cases and isolates between January 1 2016 and June 30 2021 were compiled from EPIWATCH, an open-source observatory for outbreak scanning and analysis, the World Health Organisation (WHO) and ProMed, and analysed descriptively. Reports containing cVDPV case information were included while duplicates and defective links were excluded. Data collection occurred from April 5 2021 to July 16 2021. To identify factors associated with cVDPV, a retrospective case-control study comparing socioeconomic profiles of countries which reported cVDPV with those that did not was undertaken with weighted logistic regression analysis. Findings: cVDPV caused by serotype 2 poliovirus was the predominant strain (95%) of 1818 total human cVDPV cases reported. Of 40 countries reporting cVDPV cases or isolates, 22 (55%) had polio vaccination coverages below 80%. Low vaccination coverage (Adjusted OR = 83·41, 95% CI: [5·01, 1387·71], p = 0·0020) was found to be associated with increased odds of reporting cVDPV after adjusting for confounding effects of GDP per capita, female adult literacy rates, maternal mortality rate, and Global Peace Index. Interpretation: Our findings reinforce the importance of maintaining high levels of vaccination, as risk of re-emergence rises when immunity wanes. Interventions to increase vaccination and standards of living in developing countries, coupled with robust surveillance are required if humanity hopes to eradicate polio in the near future. Funding: This research was supported by the MRFF 2021 Frontier Health and Medical Research Grant (ID RFRHPI000280), Department of Health, the Australian Government.
Language	English
Publishing date	2022-06-25
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2022.101508
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Article: The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.

Lu, Lu-Ping / Chang, Wei-Hua / Mao, Yi-Wen / Cheng, Min-Chi / Zhuang, Xiao-Yi / Kuo, Chi-Sheng / Lai, Yi-An / Shih, Tsai-Miao / Chou, Teh-Ying / Tsai, Guochuan Emil

Biomedicines

2024 Volume 12, Issue 4

Abstract: It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders ... ...

Abstract	It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.
Language	English
Publishing date	2024-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12040853
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Book ; Online: Backward Compatibility During Data Updates by Weight Interpolation

Schumann, Raphael / Mansimov, Elman / Lai, Yi-An / Pappas, Nikolaos / Gao, Xibin / Zhang, Yi

2023

Abstract: Backward compatibility of model predictions is a desired property when updating a machine learning driven application. It allows to seamlessly improve the underlying model without introducing regression bugs. In classification tasks these bugs occur in ... ...

Abstract	Backward compatibility of model predictions is a desired property when updating a machine learning driven application. It allows to seamlessly improve the underlying model without introducing regression bugs. In classification tasks these bugs occur in the form of negative flips. This means an instance that was correctly classified by the old model is now classified incorrectly by the updated model. This has direct negative impact on the user experience of such systems e.g. a frequently used voice assistant query is suddenly misclassified. A common reason to update the model is when new training data becomes available and needs to be incorporated. Simply retraining the model with the updated data introduces the unwanted negative flips. We study the problem of regression during data updates and propose Backward Compatible Weight Interpolation (BCWI). This method interpolates between the weights of the old and new model and we show in extensive experiments that it reduces negative flips without sacrificing the improved accuracy of the new model. BCWI is straight forward to implement and does not increase inference cost. We also explore the use of importance weighting during interpolation and averaging the weights of multiple new models in order to further reduce negative flips.
Keywords	Computer Science - Machine Learning ; Computer Science - Computation and Language
Subject code	310
Publishing date	2023-01-25
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Efficient Domain Adaptation of Language Models via Adaptive Tokenization

Sachidananda, Vin / Kessler, Jason S. / Lai, Yi-an

2021

Abstract: Contextual embedding-based language models trained on large data sets, such as BERT and RoBERTa, provide strong performance across a wide range of tasks and are ubiquitous in modern NLP. It has been observed that fine-tuning these models on tasks ... ...

Abstract	Contextual embedding-based language models trained on large data sets, such as BERT and RoBERTa, provide strong performance across a wide range of tasks and are ubiquitous in modern NLP. It has been observed that fine-tuning these models on tasks involving data from domains different from that on which they were pretrained can lead to suboptimal performance. Recent work has explored approaches to adapt pretrained language models to new domains by incorporating additional pretraining using domain-specific corpora and task data. We propose an alternative approach for transferring pretrained language models to new domains by adapting their tokenizers. We show that domain-specific subword sequences can be efficiently determined directly from divergences in the conditional token distributions of the base and domain-specific corpora. In datasets from four disparate domains, we find adaptive tokenization on a pretrained RoBERTa model provides >97% of the performance benefits of domain specific pretraining. Our approach produces smaller models and less training and inference time than other approaches using tokenizer augmentation. While adaptive tokenization incurs a 6% increase in model parameters in our experimentation, due to the introduction of 10k new domain-specific tokens, our approach, using 64 vCPUs, is 72x faster than further pretraining the language model on domain-specific corpora on 8 TPUs. Comment: 11 pages. SustaiNLP workshop at EMNLP 2021
Keywords	Computer Science - Computation and Language
Subject code	005
Publishing date	2021-09-15
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cinnamaldehyde decreases the invasion and u-PA expression of osteosarcoma by down-regulating the FAK signalling pathway

Chu, Shu-Chen / Hsieh, Yih-Shou / Hsu, Li-Sung / Lin, Chin-Yin / Lai, Yi-An / Chen, Pei-Ni

Food & function. 2022 June 20, v. 13, no. 12

2022

Abstract: Cancer metastasis is the major cause of the high mortality risk of patients with osteosarcoma. Cinnamaldehyde has been shown to exhibit multiple tumour-suppressing activities, but its role in human osteosarcoma is not yet completely defined. In this ... ...

Abstract	Cancer metastasis is the major cause of the high mortality risk of patients with osteosarcoma. Cinnamaldehyde has been shown to exhibit multiple tumour-suppressing activities, but its role in human osteosarcoma is not yet completely defined. In this study, the antimetastatic effect of cinnamaldehyde on highly metastatic human osteosarcoma cells was observed in vitro and in vivo using Saos-2 and 143B cells. Cinnamaldehyde reduced the activity and protein level of urokinase-type plasminogen activator (u-PA) and suppressed the invasion ability of osteosarcoma cells by inhibiting the phosphorylation of focal adhesion kinase. In addition, cinnamaldehyde reduced cell movement, cell–matrix adhesion, and the expression of the mesenchymal markers of epithelial-to-mesenchymal transition, namely, fibronectin and N-cadherin. Importantly, the oral administration of cinnamaldehyde remarkably suppressed the pulmonary metastasis of osteosarcoma in mice. Results indicated that cinnamaldehyde has therapeutic potential for inhibiting osteosarcoma metastasis.
Keywords	cadherins ; cell adhesion ; cell movement ; fibronectins ; humans ; metastasis ; mortality ; non-specific protein-tyrosine kinase ; oral administration ; osteosarcoma ; phosphorylation ; protein content ; risk ; u-plasminogen activator
Language	English
Dates of publication	2022-0620
Size	p. 6574-6582.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d2fo00634k
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: NO Reduction to N

Wu, Wun-Yan / Tsai, Ming-Li / Lai, Yi-An / Hsieh, Chieh-Hsin / Liaw, Wen-Feng

Inorganic chemistry

2021 Volume 60, Issue 21, Page(s) 15874–15889

Abstract: In spite of the comprehensive study of the metal-mediated conversion of NO to ... ...

Abstract	In spite of the comprehensive study of the metal-mediated conversion of NO to N
MeSH term(s)	Iron ; Nitrogen Oxides
Chemical Substances	Nitrogen Oxides ; dinitrosyl iron complex (68586-27-6) ; Iron (E1UOL152H7)
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1484438-2
ISSN	1520-510X ; 0020-1669
ISSN (online)	1520-510X
ISSN	0020-1669
DOI	10.1021/acs.inorgchem.1c00541
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