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7S,8R-dihydroxydeepoxysarcophytoxide: A natural dihydrofuranocembranoid from the octocoral Sarcophyton stellatum

phytochemistry Letters 2024年 63卷 14-17页

作者： Sheu, Jyh-Horng Zheng, Li-Guo Chen, You-Ying Chien, Su-Ying Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Chinese Medicine Research and Development Center China Medical University Hospital National Museum of Marine Biology and Aquarium Instrumentation Center National Taiwan University Graduate Institute of Natural Products Kaohsiung Medical University Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University

Chemical screening of the octocoral Sarcophyton stellatum led to the isolation of a natural dihydrofuranocembranoid, 7S,8R-dihydroxydeepoxysarcophytoxide (1). Single-crystal X-ray diffraction analysis was conducted to determine the absolute configuration of 1, and its structure was confirm using two-dimensional NMR experiments and a literature review. dihydrofuranocembranoid 1 actively enhanced alkaline phosphatase activity. © 2024 phytochemical Society of Europe

关键词： Absolute configuration Alkaline phosphatase dihydrofuranocembranoid Sarcophytoxide

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Structure-guided identification and characterization of potent inhibitors targeting phoP and MtrA to combat mycobacteria

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Computational and Structural biotechnology Journal 2024年 23卷 1477-1488页

作者： Su, Han-Li Lai, Shu-Jung Tsai, Keng-Chang Fung, Kit-Man Lung, Tse-Lin Hsu, Hsing-Mien Wu, Yi-Chen Liu, Ching-Hui Lai, Hui-Xiang Lin, Jiun-Han Tseng, Tien-Sheng Department of Emergency Medicine Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi City600 Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Research Center for Cancer Biology China Medical University Taichung Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan Academia Sinica Taipei11529 Taiwan Institute of Molecular Biology National Chung Hsing University Taichung Taiwan Department of Industrial Technology Ministry of Economic Affairs Taipei Taiwan Food Industry Research and Development Institute Hsinchu City Taiwan

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators phoP and MtrA of mycobacteria. The constructed pharmacophore model phar-PR-n4 identified effective inhibitors of formation of the phoP–dNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (Kd = 18.4 ± 4.3 μM) and ST132 (Kd = 14.5 ± 0.1 μM) strongly targeted phoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of phoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of phoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria. © 2024 The Authors

关键词： Antimicrobial agents

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Structure-Guided discovery of Pd-1/Pd-L1 Interaction Inhibitors: Peptide design, Screening, and Optimization via Computation-Aided phage display Engineering

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Journal of Chemical Information and Modeling 2024年第5期64卷 1615-1627页

作者： Tseng, Tien-Sheng Lee, Chao-Chang Chen, Po-Juei Lin, Chiu-Yuen Chen, Wang-Chuan Lee, Yu-Ching Lin, Jiun-Han Chen, Kaun-Wen Tsai, Keng-Chang Institute of Molecular Biology National Chung Hsing University Taichung40202 Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei11221 Taiwan The School of Chinese Medicine for Post Baccalaureate I-Shou University Kaohsiung824005 Taiwan Department of Chinese Medicine E-Da Hospital Kaohsiung824005 Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei11031 Taiwan Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Department of Industrial Technology Ministry of Economic Affairs Taipei100210 Taiwan Food Industry Research and Development Institute Hsinchu30062 Taiwan Molecular Science and Digital Innovation Center Genetics Generation Advancement Corporation Taipei11949 Taiwan

Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The Pd-1/Pd-L1 immune checkpoint modulates interactions between tumor cells and T cells and has been extensively targeted in cancer immunotherapy. However, the monoclonal antibodies known to target this immune checkpoint have considerable side effects, and novel Pd-1/Pd-L1 inhibitors are therefore required. Herein, a peptide inhibitor to disrupt Pd-1/Pd-L1 interactions was designed through structure-driven phage display engineering coupled to computational modification and optimization. BetaPb, a novel peptide library constructed by using the known structure of Pd-1/Pd-L, was used to develop inhibitors against the immune checkpoint, and specific peptides with high affinity toward Pd-1 were screened through enzyme-linked immunosorbent assays, homogeneous time-resolved fluorescence, and biolayer interferometry. A potential inhibitor, B8, was preliminarily screened through biopanning. The binding affinity of B8 toward Pd-1 was confirmed through computation-aided optimization. Assessment of B8 variants (B8.1, B8.2, B8.3, B8.4, and B8.5) demonstrated their attenuation of Pd-1/Pd-L1 interactions. B8.4 exhibited the strongest attenuation efficiency at a half-maximal effective concentration of 0.1 μM and the strongest binding affinity to Pd-1 (equilibrium dissociation constant = 0.1 μM). B8.4 outperformed the known Pd-1/Pd-L1 interaction inhibitor PL120131 in disrupting Pd-1/Pd-L1 interactions, revealing that B8.4 has remarkable potential for modification to yield an antitumor agent. This study provides valuable information for the future development of peptide-based drugs, therapeutics, and immunotherapies for cancer. © 2024 American Chemical Society.

关键词： Peptides

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Sinulariaone A: a novel diterpenoid with a 13-membered carbocyclic skeleton from an octocoral Sinularia species

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RSC Advances 2023年第15期13卷 10408-10413页

作者： Tseng, Hsuan-Jung Kuo, Liang-Mou Tsai, Yu-Chi Hu, Hao-Chun Chen, Po-Jen Chien, Su-Ying Sheu, Jyh-Horng Sung, Ping-Jyun Graduate Institute of Marine Biology National Dong Hwa University Pingtung944401 Taiwan National Museum of Marine Biology & Aquarium Pingtung944401 Taiwan Department of General Surgery Chang Gung Memorial Hospital at Chiayi Chiayi613016 Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung404333 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung807378 Taiwan Clinical Immunology Laboratory Department of Medical Research E-Da Hospital I-Shou University Kaohsiung824005 Taiwan Instrumentation Center National Taiwan University Taipei106319 Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung804201 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung404394 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City242062 Taiwan

Chemical composition screening of an octocoral identified as Sinularia species led to the isolation of a novel diterpenoid, sinulariaone A (1), featuring a 13-membered carbocyclic skeleton. The structure of 1 was established by spectroscopic elucidation, computed calculation, and X-ray diffraction analysis. Moreover, a single-crystal X-ray diffraction analysis of chlorofurancembranoid B (2), obtained in our previous study from the same octocoral species, was reported for the first time to demonstrate the absolute configuration. diterpenoid 1 showed cytotoxicity towards human promyelocytic leukemia HL-60 cells, with an IC50 value of 38.01 μM. © 2023 The Royal Society of Chemistry.

关键词： X ray powder diffraction

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development of BACE2-IN-1/tranylcypromine-based compounds to induce steroidogenesis-dependent neuroprotection

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Biomedicine and pharmacotherapy 2025年 183卷 117851-117851页

作者： Banerjee, Suddhasatwa Hsu, Ying-Ting Nguyen, duc-Hieu Yeh, Shiu-Hwa Liou, Ke-Chi Liu, Jr-Jiun Liou, Jing-Ping Chuang, Jian-Ying School of Pharmacy Taipei Medical University Taipei 11031 Taiwan Ph.D. Program in Medical Neuroscience Taipei Medical University and National Health Research Institutes Taipei 11031 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli County 35053 Taiwan TMU Research Center for Drug Discovery Taipei Medical University Taipei 11031 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei 110 Taiwan International Master Program in Medical Neuroscience Taipei Medical University New Taipei City 23564 Taiwan TMU Research Center of Neuroscience Taipei Medical University Taipei 11031 Taiwan Department of Biomedical Science and Environmental Biology Kaohsiung Medical University Kaohsiung 80780 Taiwan

Traumatic brain injury (TBI) constitutes a significant burden on global healthcare systems, especially affecting younger populations, where it is a leading cause of disability and mortality. Current treatments for TBI mainly focus on preventing further brain damage and controlling symptoms. However, despite these approaches, several clinical needs remain unmet. Revelations from single-cell RNA sequencing (scRNA-seq) performed to determine cell-type heterogeneity and gene expression changes in brain tissue indicated that brain trauma increases the expression of lysine-specific demethylase 1 (LSd1) and secretase 2 (BACE2). To capitalize on this finding, a medicinal chemistry campaign was conducted to pragmatically insert tranylcypromine, an LSd1 inhibitor, into a carefully designed BACE2 inhibitory template (BACE2-IN-1). Additionally, tranylcypromine was structurally modified to enhance the effects of LSd1 inhibition in TBI. As a result, a tractable neuroprotective agent, BACE2-IN-1/tranylcypromine-based compound 4, was identified, showing potential to maintain Neuro-2a cell survival by alleviating mitochondrial damage after oxidative stress. Compound 4 also restored TBI-mediated inhibition of the cholesterol biosynthetic pathway (mevalonate pathway) and damage of redox metabolism, increasing neuroprotective effects. Furthermore, behavioral assays, including nest-building and cognitive performance tests, demonstrated significant improvement in mice post-TBI following treatment with compound 4. Taken together, the outcomes of this study validate the favorable effects of inhibiting LSd1 and beta-secretase in mitigating mitochondrial stress and promoting neurometabolic recovery in TBI. These findings pave the way for the development of rationally designed inhibitors as promising neuroprotective agents, potentially addressing unmet clinical needs in TBI treatment. © 2025 The Authors

关键词： Beta-secretase LSd1 Oxidative stress Sterol biosynthesis Tranylcypromine Traumatic brain injury

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Prediction tools for assessing functional impacts of gene mutations in Clear Cell Renal Cell Carcinoma: A comparative study

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Computers in Biology and Medicine 2025年第Pt A期192卷 110187-110187页

作者： Yang, Cheng-Hong Lin, Guan-Cheng Wu, Chih-Hsien Chen, Jin-Bor Chuang, Li-Yeh Department of Information Management Tainan University of Technology Tainan Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung Taiwan Division of Nephrology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Taiwan Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering I-Shou University Kaohsiung Taiwan Taiwan

Renal cell carcinoma (RCC) is a well-known malignancy characterized by specific gene mutations that elevate its occurrence. It can be categorized into clear cell RCC (ccRCC), papillary RCC, and chromophobe RCC, which account for approximately 85 % of all primary RCC cases. The mutations typically involve single-nucleotide variants (SNVs) that lead to amino acid substitutions, which influence various biological functions, including gene expression. Therefore, predicting the functional consequences of RCC-related single-nucleotide polymorphisms (SNPs), including substitutions, insertions, deletions, and duplications, is crucial for the effective clinical management of RCC. In recent years, the accessibility and popularity of tools for predicting SNP functional variations have grown, especially in research concerning the potential risks associated with key gene mutations in cancer. Accordingly, this study focused on commonly mutated genes in ccRCC, namely VHL, BAP1, PBRM1, and SETd2. Public data from sources such as The Cancer Genome Atlas and the National Center for biotechnology Information were used to identify 61 gene mutation positions. Nine nonsynonymous mutation prediction tools were used for analysis, namely SIFT, Polyphen-2, Mutation Assessor, Fathmm, MutPred, CHASM, Revel, Provean, and SNP&GO. The tools were evaluated by their statistical performance, prediction distribution, and receiver operating characteristic curves. The three tools with the highest accuracy for predicting the functional consequences of mutations in the four frequently mutated genes associated with ccRCC were SIFT (accuracy of 0.75), Provean (0.7), and Polyphen-2 (0.69). These findings offer valuable insights into predicting ccRCC-related gene mutation effects, but further research and validation are essential to support their clinical applications. © 2025

关键词： Transcription

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16-Hydroxybriaranes from the octocoral Briareum stechei

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phytochemistry Letters 2023年第1期57卷 92-95页

作者： Liu, Chia-Jung Wang, Chien-Chiao Chang, Chun-Feng Zhang, Mingzi M. Tsou, Lun Kelvin Wen, Zhi-Hong Hwang, Tsong-Long Chen, You-Ying Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung 804201 Taiwan National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Graduate Institute of Natural Products College of Medicine Chang Gung University Taoyuan 333323 Taiwan Graduate Institute of Biomedical Sciences College of Medicine Chang Gung University Taoyuan 333323 Taiwan Division of Urology Department of Surgery Kaohsiung Armed Forces General Hospital Kaohsiung 802301 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli Zhunan 350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli Zhunan 350401 Taiwan Department of Anesthesiology Chang Gung Memorial Hospital Taoyuan 333008 Taiwan Research Center for Chinese Herbal Medicine Graduate Institute of Healthy Industry Technology College of Human Ecology Chang Gung University of Science and Technology Taoyuan 333324 Taiwan Department of Chemical Engineering Ming Chi University of Technology New Taipei 243303 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung 404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung 807378 Taiwan Ph.D. Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City 242062 Taiwan

Two new 16-hydroxybriaranes, 11-dehydroxybriavioid B (1) and 12-epi-briastecholide L (2), have been isolated from an algal-containing octocoral identified as Briareum stechei. The structures of metabolites 1 and 2 were corroborated by extensive 2d-NMR studies and comparison with literature data. Briarane 2 was found to reduce the release of inducible nitric oxide synthase (iNOS) to 87.92 %, at a concentration of 10 μM. © 2023 phytochemical Society of Europe

关键词： Briarane Briareum stechei Briastecholide Briavioid iNOS

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Reporting ethical approval in case reports and case series in 12 consecutive years: A systematic review

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Health Care Science 2024年第5期3卷 298-311页

作者： Linh Tran Vuong Thanh Huan Luu Lam Thang Tai Adnan Safi Moustafa ElBadry Ahmed Mohamed Osman Algazar Sedighe Karimzadeh Nguyen Vinh Khang Nguyen Hai Nam Zaheer Ahmad Qureshi Nguyen Lam Vuong Le Huu Nhat Minh Nguyen Tien Huy University of Health Sciences Vietnam National University Ho Chi Minh CityHo Chi Minh CityVietnam Department of Sport Medicine Pham Ngoc Thach University of MedicineHo Chi Minh CityVietnam Department of Cardiology City Children HospitalHo Chi Minh CityVietnam Department of Medicine Lahore General HospitalLahorePakistan Faculty of Medicine Sohag UniversitySohagEgypt Neurology Department Alharam HospitalGizaEgypt Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical SciencesUniversity of California IrvineIrvineCaliforniaUSA Department of Neurology University Medical CenterHo Chi Minh CityVietnam Department of Liver Tumor Cancer CenterCho Ray HospitalHo Chi Minh CityVietnam Liver Transplant Unit Cancer CenterCho Ray HospitalHo Chi Minh CityVietnam The Frank H.Netter M.D School of Medicine at Quinnipiac University BridgeportUSA Department of Medical Statistics and Informatics Faculty of Public HealthUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam International Ph.D.Program in Medicine College of MedicineTaipei Medical UniversityTaipeiTaiwanChina Global Clinical Scholars Research Training Program Harvard Medical SchoolBostonMassachusettsUSA Institute of Research and Development Duy Tan UniversityDa NangVietnam School of Medicine and Pharmacy Duy Tan UniversityDa NangVietnam School of Tropical Medicine and Global Health(TMGH) Nagasaki UniversityNagasakiJapan

Our study describes the reported rate of the Institutional Review Board(IRB)approval,declaration of Helsinki(doH),and informed consent in the case reports and case series and investigates factors associated with the ethical approval *** searched PubMed for case reports and case series from 2006 to ***,we obtained the first 20 articles of a case report cluster from 20 distinct *** analysis initially contained at least 2400 papers,with 100 papers each study design and *** 26(5.4%)of 480 included studies reported IRB approval,doH approval,and participant informed consent;58(12.1%)reported two out of three ethical statements(doH,informed consent,IRB);and 151(31.5%)reported only one,leading to nearly 245 studies(51.0%)did not report any ethical approval *** clusters mentioned the doH the *** years,ages,ethical item types,and cluster types were associated with ethical reporting *** study found the serious under‐reporting of ethical practices in both case reports and case series.

关键词： case report case series ethical approval declaration of Helsinki institutional review board informed consent

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Polymethoxyflavone from Citrus depressa as an inhibitor against various variants of SARS-CoV-2 spike protein

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Journal of Ethnopharmacology 2024年 320卷 117412页

作者： Liu, Ta-Wei Hsu, Su-Jung Hsieh, Yves S.Y. Liu, Hui-Kang Lee, Ching-Kuo School of Pharmacy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Division of Glycoscience Department of Chemistry School of Engineering Sciences in Chemistry Biotechnology and Health KTH Royal Institute of Technology AlbaNova University Centre Stockholm SE106 91 Sweden National Research Institute of Chinese Medicine (NRICM) Ministry of Health and Welfare Taipei City Taiwan Ph. D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei Taiwan

Ethnopharmacological relevance: In traditional Taiwanese medicine, Citrus depressa Hayata serves as the raw material of Chen-Pi which has been widely used to treat respiratory ailments. Scientific investigations have validated the attributes of C. depressa, elucidating its valuable properties, including antioxidative, anti-inflammatory, anticancer, neuroprotion, hepatoprotection, and hypolipidemic effects. Aim of the study: This study aims to isolate a universal inhibitor of the SARS-CoV-2 spike protein from C. depressa and confirm the mechanism by which these inhibitors disrupt the binding of the spike protein to hACE2. Materials and methods: The whole fruit of C. depressa was subjected to ethanol extraction, following by partitioning to obtain water, butanol, and ethyl acetate fractions. To identify the inhibitory components in citrus fruits, we performed both the SPR assay and the SARS-CoV-2 pseudo-virus assays. Subsequently, we employed a bioassay-guided approach to efficiently isolate and characterize the bioactive constituents that hindered the interaction between the SARS-CoV-2 spike protein and hACE2, using a combination of MPLC and Semi-preparative HPLC for compound isolation. ELISA based spike protein binding assay evaluate the inhibitory activities of the extract and potential constituents against multiple spike protein variants. To further shed light on the inhibitory mechanism, candidate inhibitors were validated through the SPR assay and molecular docking. Results: The crude extract and ethyl acetate layer derived from C. depressa showed significant inhibitory activity on SARS-CoV-2 Omicron BA.4/5, with IC₅₀ of 77.4 μg/mL and 100 μg/mL, respectively. Ten potential compounds from C. depressa have been identified with inhibitory activity against various SARS-CoV-2 spike proteins. 2′-hydroxy-4,4′,5′,6′-tetramethoxychalcone (Cd3) and 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (Cd8) also showed good inhibitory activity to the spike protein, with K

关键词： ACE-2 Citrus depress Polymethoxyflavone SARS-CoV-2 Spike protein

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Biological Evaluation of Sulfonate and Sulfate Analogues of Lithocholic Acid: A Bioisosterism-Guided Approach Towards the discovery of Potential Sialyltransferase Inhibitors for Antimetastatic Study

SSRN

引用

SSRN 2023年

作者： Perez, Ser John Lynon P. Chen, Chia-Ling Chang, Tzu-Ting Li, Wen-Shan Institute of Chemistry Academia Sinica Taipei115 Taiwan Department of Applied Chemistry National Yang Ming Chiao Tung University Hsinchu300 Taiwan Sustainable Chemical Science and Technology Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Biomedical Translation Research Center Academia Sinica Taipei115 Taiwan Department of Medicinal and Applied Chemistry College of Life Science Kaohsiung Medical University Kaohsiung807 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung804 Taiwan Department of Chemistry College of Science Tamkang University New Taipei City251 Taiwan

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MdA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis. © 2023, The Authors. All rights reserved.

关键词： Sulfur compounds

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