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  1. Article ; Online: Transcriptome-wide association study coupled with eQTL analysis reveals the genetic connection between gene expression and flowering time in Arabidopsis.

    Chien, Pei-Shan / Chen, Pin-Hua / Lee, Cheng-Ruei / Chiou, Tzyy-Jen

    Journal of experimental botany

    2023  Volume 74, Issue 18, Page(s) 5653–5666

    Abstract: Genome-wide association study (GWAS) has improved our understanding of complex traits, but challenges exist in distinguishing causation versus association caused by linkage disequilibrium. Instead, transcriptome-wide association studies (TWAS) detect ... ...

    Abstract Genome-wide association study (GWAS) has improved our understanding of complex traits, but challenges exist in distinguishing causation versus association caused by linkage disequilibrium. Instead, transcriptome-wide association studies (TWAS) detect direct associations between expression levels and phenotypic variations, providing an opportunity to better prioritize candidate genes. To assess the feasibility of TWAS, we investigated the association between transcriptomes, genomes, and various traits in Arabidopsis, including flowering time. The associated genes formerly known to regulate growth allometry or metabolite production were first identified by TWAS. Next, for flowering time, six TWAS-newly identified genes were functionally validated. Analysis of the expression quantitative trait locus (eQTL) further revealed a trans-regulatory hotspot affecting the expression of several TWAS-identified genes. The hotspot covers the FRIGIDA (FRI) gene body, which possesses multiple haplotypes differentially affecting the expression of downstream genes, such as FLOWERING LOCUS C (FLC) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1). We also revealed multiple independent paths towards the loss of function of FRI in natural accessions. Altogether, this study demonstrates the potential of combining TWAS with eQTL analysis to identify important regulatory modules of FRI-FLC-SOC1 for quantitative traits in natural populations.
    MeSH term(s) Arabidopsis/metabolism ; Transcriptome ; Quantitative Trait Loci/genetics ; Genome-Wide Association Study ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism
    Chemical Substances Arabidopsis Proteins ; FRI protein, Arabidopsis
    Language English
    Publishing date 2023-07-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2976-2
    ISSN 1460-2431 ; 0022-0957
    ISSN (online) 1460-2431
    ISSN 0022-0957
    DOI 10.1093/jxb/erad262
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Exploring fNIRS-Based Brain State Recognition and Visualization through the use of Explainable Convolutional Neural Networks.

    Chen, Pin-Hua / Wei, Chun-Shu / Lan, Chen-Chia / Chen, Nai-Feng / Wang, Li-Chun

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

    2023  Volume 2023, Page(s) 1–4

    Abstract: Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that has grown vigorously in recent years. With noticeable attention, machine learning methods have also been applied to fNIRS. However, the current approach lacks interpretability ...

    Abstract Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that has grown vigorously in recent years. With noticeable attention, machine learning methods have also been applied to fNIRS. However, the current approach lacks interpretability of the results. In recent years, the utilization and investigation of fNIRS have experienced significant growth and are now being utilized in clinical research. However, the collection of clinical fNIRS data is limited in sample size. Therefore, our aim is to utilize the collected fNIRS data from all channels and achieve interpretable analysis results with minimal human manipulation, channel selection or feature extraction. We developed an fNIRS-based interpretable model and used class-specific gradient information to visualize the biomarkers captured by the model via locating the important region. The accuracy of our model's classification was 6% higher than that of the conventional SVM method under within-subject classification. The model focuses on signals from the left brain in the classification of right-hand finger tapping task, while in the task of classifying left-handed movements, the model relies on signals from the right brain. These results were consistent with current understanding of physiology.Clinical Relevance- The machine learning-based fNIRS model has the potential to be used for the diagnosis and prediction of therapeutic efficacy in clinical settings.
    MeSH term(s) Humans ; Spectroscopy, Near-Infrared/methods ; Brain/diagnostic imaging ; Neural Networks, Computer ; Hand ; Cerebral Cortex
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2694-0604
    ISSN (online) 2694-0604
    DOI 10.1109/EMBC40787.2023.10341196
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: S‐Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice

    Chen, Pin‐Hua / Chang, Chun‐Han / Lin, Wei‐Sheng / Nagabhushanam, Kalyanam / Ho, Chi‐Tang / Pan, Min‐Hsiung

    Molecular nutrition & food research. 2022 Apr., v. 66, no. 7

    2022  

    Abstract: SCOPE: S‐Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms ...

    Abstract SCOPE: S‐Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms is evaluated. METHODS AND RESULTS: When mice have attained reproductive senescence at 60 weeks of age, SAC is supplemented to 0.05% and 0.2% into their normal diet for 12 weeks. The results show that SAC could significantly improve the level of hepatic optic atrophy 1 (OPA1) mRNA, which is a key factor for mitochondrial fusion, and consequently elevated the mitochondrial biogenesis‐related proteins sirtuin 1 (SIRT1) and peroxisome proliferator‐activated receptor‐gamma coactivator‐1 alpha (PGC‐1α), thus ameliorating oxidative stress, such as malondialdehyde (MDA) in the liver and 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG) in urine. Among the biochemical markers of aging, SAC significantly reduces liver galactosidase β1 (GLB1) and senescence‐associated β‐galactosidase (SA‐βgal), which are induced by replicative senescence. The mitochondria with green fluorescent protein (GFP)‐tagged transgenic strain SJ4103 C. elegans is incubated with 5 or 50 µM SAC, and SAC treated groups maintain the linear morphology of mitochondria. CONCLUSION: SAC regulates mitochondrial dynamics and ameliorated aging to a significant degree. This study also confirms that mitochondrial dynamics are a promising target for screening materials to combat aging and as a direction for anti‐aging product development.
    Keywords Caenorhabditis elegans ; atrophy ; cell senescence ; diet ; food research ; garlic ; genetically modified organisms ; green fluorescent protein ; liver ; males ; malondialdehyde ; mitochondria ; oxidative stress ; peroxisome proliferator-activated receptor gamma ; product development ; sirtuins ; urine
    Language English
    Dates of publication 2022-04
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 2160372-8
    ISSN 1613-4133 ; 1613-4125
    ISSN (online) 1613-4133
    ISSN 1613-4125
    DOI 10.1002/mnfr.202101077
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent.

    Nirosha Yalamandala, Bhanu / Chen, Pin-Hua / Moorthy, Thrinayan / Huynh, Thi My Hue / Chiang, Wen-Hsuan / Hu, Shang-Hsiu

    Pharmaceutics

    2022  Volume 14, Issue 3

    Abstract: Nano-catalytic agents actuating Fenton-like reaction in cancer cells cause intratumoral generation of reactive oxygen species (ROS), allowing the potential for immune therapy of tumor metastasis via the recognition of tumor-associated antigens. However, ... ...

    Abstract Nano-catalytic agents actuating Fenton-like reaction in cancer cells cause intratumoral generation of reactive oxygen species (ROS), allowing the potential for immune therapy of tumor metastasis via the recognition of tumor-associated antigens. However, the self-defense mechanism of cancer cells, known as autophagy, and unsustained ROS generation often restricts efficiency, lowering the immune attack, especially in invading metastatic clusters. Here, a functional core-shell metal-organic framework nanocube (dual MOF) doubling as a catalytic agent and T cell infiltration inducer that programs ROS and inhibits autophagy is reported. The dual MOF integrated a Prussian blue (PB)-coated iron (Fe
    Language English
    Publishing date 2022-02-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics14030527
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice.

    Chen, Pin-Hua / Chang, Chun-Han / Lin, Wei-Sheng / Nagabhushanam, Kalyanam / Ho, Chi-Tang / Pan, Min-Hsiung

    Molecular nutrition & food research

    2022  Volume 66, Issue 7, Page(s) e2101077

    Abstract: Scope: S-Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying ... ...

    Abstract Scope: S-Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms is evaluated.
    Methods and results: When mice have attained reproductive senescence at 60 weeks of age, SAC is supplemented to 0.05% and 0.2% into their normal diet for 12 weeks. The results show that SAC could significantly improve the level of hepatic optic atrophy 1 (OPA1) mRNA, which is a key factor for mitochondrial fusion, and consequently elevated the mitochondrial biogenesis-related proteins sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), thus ameliorating oxidative stress, such as malondialdehyde (MDA) in the liver and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Among the biochemical markers of aging, SAC significantly reduces liver galactosidase β1 (GLB1) and senescence-associated β-galactosidase (SA-βgal), which are induced by replicative senescence. The mitochondria with green fluorescent protein (GFP)-tagged transgenic strain SJ4103 C. elegans is incubated with 5 or 50 µM SAC, and SAC treated groups maintain the linear morphology of mitochondria.
    Conclusion: SAC regulates mitochondrial dynamics and ameliorated aging to a significant degree. This study also confirms that mitochondrial dynamics are a promising target for screening materials to combat aging and as a direction for anti-aging product development.
    MeSH term(s) Aging/genetics ; Animals ; Caenorhabditis elegans/metabolism ; Cysteine/analogs & derivatives ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondrial Dynamics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Sirtuin 1/metabolism
    Chemical Substances Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; S-allylcysteine (81R3X99M15) ; Sirtuin 1 (EC 3.5.1.-) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2022-02-11
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2160372-8
    ISSN 1613-4133 ; 1613-4125
    ISSN (online) 1613-4133
    ISSN 1613-4125
    DOI 10.1002/mnfr.202101077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Lung metastasis-Harnessed in-Situ adherent porous organic nanosponge-mediated antigen capture for A self-cascaded detained dendritic cells and T cell infiltration.

    Wu, Ting-Hsien / Lu, Yu-Jen / Chiang, Min-Ren / Chen, Pin-Hua / Lee, Yu-Sheng / Shen, Ming-Yin / Chiang, Wen-Hsuan / Liu, Yu-Chen / Chuang, Chun-Yu / Amy Lin, Hsiao-Chun / Hu, Shang-Hsiu

    Biomaterials

    2023  Volume 305, Page(s) 122443

    Abstract: The infiltration of cytotoxic T lymphocytes promises to suppress the most irresistible metastatic tumor for immunotherapy, yet immune privilege and low immunogenic responses in these aggressive clusters often restrict lymphocyte recruitment. Here, an in ... ...

    Abstract The infiltration of cytotoxic T lymphocytes promises to suppress the most irresistible metastatic tumor for immunotherapy, yet immune privilege and low immunogenic responses in these aggressive clusters often restrict lymphocyte recruitment. Here, an in situ adherent porous organic nanosponge (APON) doubles as organ selection agent and antigen captor to overcome immune privilege is developed. With selective organ targeting, the geometric effect of APON composed of disc catechol-functionalized covalent organic framework (COF) boosts the drug delivery to lung metastases. Along with a self-cascaded immune therapy, the therapeutic agents promote tumor release of damage-associated molecular patterns (DAMPs), and then, in situ deposition of gels to capture these antigens. Furthermore, APON with catechol analogs functions as a reservoir of antigens and delivers autologous DAMPs to detain dendritic cells, resulting in a sustained enhancement of immunity. This disc sponges (APON) at lung metastasis as antigen reservoirs and immune modulators effectively suppress the tumor in 60 days and enhanced the survival rate.
    MeSH term(s) Humans ; Porosity ; Lung Neoplasms ; T-Lymphocytes, Cytotoxic ; Immunotherapy ; Antigens, Neoplasm ; Dendritic Cells ; Catechols
    Chemical Substances Antigens, Neoplasm ; Catechols
    Language English
    Publishing date 2023-12-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene.

    Wong, Swee-Hee / Wang, Wen-Hung / Chen, Pin-Hua / Li, Shuan-Yow / Yang, Jiann-Jou

    International journal of medical sciences

    2017  Volume 14, Issue 3, Page(s) 246–256

    Abstract: In a previous study, we identified a novel missense mutation, p.W77S, in ... ...

    Abstract In a previous study, we identified a novel missense mutation, p.W77S, in the
    MeSH term(s) Connexins/chemistry ; Connexins/genetics ; Connexins/metabolism ; Deafness/genetics ; Deafness/pathology ; Endoplasmic Reticulum/chemistry ; Endoplasmic Reticulum/genetics ; Gap Junctions/genetics ; Gap Junctions/pathology ; Gene Expression Regulation ; HeLa Cells ; Humans ; Lysosomes/genetics ; Mutation, Missense ; Nerve Tissue Proteins/chemistry ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Protein Domains ; Proteolysis ; Structure-Activity Relationship
    Chemical Substances Connexins ; GJC3 protein, human ; Nerve Tissue Proteins
    Language English
    Publishing date 2017
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2151424-0
    ISSN 1449-1907 ; 1449-1907
    ISSN (online) 1449-1907
    ISSN 1449-1907
    DOI 10.7150/ijms.17785
    Database MEDical Literature Analysis and Retrieval System OnLINE

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