المؤلفون: Selvaraj, Sanjay Prasad, Lin, Kuan-Hung, Lin, Wen-Chun, You, Ming-Feng, Li, Tsung-Lin, Chen, Jyh-Yih

المساهمون: Ministry of Education, National Science and Technology Council, Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica

المصدر: ACS Omega ; volume 9, issue 27, page 29756-29764 ; ISSN 2470-1343 2470-1343

الإتاحة: https://doi.org/10.1021/acsomega.4c03352Test

المؤلفون: Chen, Chih-Hao, Lee, Chung-Wei, Hsieh, Yi-Chen, Lin, Chun-Jen, Chen, Yu-Wei, Lin, Kuan-Hung, Sung, Pi-Shan, Tang, Chih-Wei, Chu, Hai-Jui, Tsai, Kun-Chang, Chou, Chao-Liang, Lin, Ching-Huang, Wei, Cheng-Yu, Yen, Shang-Yih, Chen, Po-Lin, Yeh, Hsu-Ling, Chan, Lung, Sung, Sheng-Feng, Lee, Meng, Liu, Hon-Man, Lin, Yen-Heng, Lee, I-Hui, Yeh, Shin-Joe, Lien, Li-Ming, Chiou, Hung-Yi, Lee, Jiunn-Tay, Tang, Sung-Chun, Jeng, Jiann-Shing, Lee, Chung-Wen, Lee, Bo-Ching, Chung, Tai-Chun, Chi, Nai-Fang, Hsu, Li-Chi, Chung, Chih-Ping, Liu, Hung-Yu, Luo, Chao-Bao, Chang, Feng-Chi, Lin, Chung-Jung, Wu, Chia-Hung, Yu, Kai-Wei, Hwang, Hsuen-En, Lin, Te-Ming

المصدر: Stroke ; volume 55, issue 3, page 532-540 ; ISSN 0039-2499 1524-4628

الوصف: BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician’s discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b–3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40–0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88–3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0–2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28–2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43–1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment ...

الإتاحة: https://doi.org/10.1161/strokeaha.123.045851Test

المؤلفون: Wang, Chun-Min, Chang, Yu-Ming, Tzeng, Ray-Chang, Chen, Tsang-Shan, Wu, Shang-Te, Lin, Kuan-Hung, Chang, Che-Chao, Huang, Meng-Hua, Vong, Si-Chon, Wu, Mu-Han, Chen, Chih-Hung, Lin, Che-Wei, Sung, Pi-Shan

المساهمون: National Cheng Kung University Hospital, Ministry of Education, National Cheng Kung University

المصدر: Journal of the Formosan Medical Association ; ISSN 0929-6646

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.1016/j.jfma.2024.02.002Test
https://api.elsevier.com/content/article/PII:S0929664624000895?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0929664624000895?httpAccept=text/plainTest

المؤلفون: Lin, Kuan‐Hung, Lyu, Syue‐Yi, Yeh, Hsien‐Wei, Li, Yi‐Shan, Hsu, Ning‐Shian, Huang, Chun‐Man, Wang, Yung‐Lin, Shih, Hao‐Wei, Wang, Zhe‐Chong, Wu, Chang‐Jer, Li, Tsung‐Lin

المصدر: Protein Science. 29(7)

مصطلحات موضوعية: Inorganic Chemistry, Chemical Sciences, Amycolatopsis, Bacterial Proteins, Catalytic Domain, Flavins, Mixed Function Oxygenases, Oxidation-Reduction, Baeyer-Villiger oxidation, flavin mononucleotide, mandelate oxidase, monooxygenase, oxidative decarboxylation, Biochemistry and Cell Biology, Computation Theory and Mathematics, Other Information and Computing Sciences, Biophysics, Biochemistry and cell biology, Medicinal and biomolecular chemistry

الوصف: Though reactive flavin-N5/C4α-oxide intermediates can be spectroscopically profiled for some flavin-assisted enzymatic reactions, their exact chemical configurations are hardly visualized. Structural systems biology and stable isotopic labelling techniques were exploited to correct this stereotypical view. Three transition-like complexes, the α-ketoacid…N5-FMNox complex (I), the FMNox -N5-aloxyl-C'α- -C4α+ zwitterion (II), and the FMN-N5-ethenol-N5-C4α-epoxide (III), were determined from mandelate oxidase (Hmo) or its mutant Y128F (monooxygenase) crystals soaked with monofluoropyruvate (a product mimic), establishing that N5 of FMNox an alternative reaction center can polarize to an ylide-like mesomer in the active site. In contrast, four distinct flavin-C4α-oxide adducts (IV-VII) from Y128F crystals soaked with selected substrates materialize C4α of FMN an intrinsic reaction center, witnessing oxidation, Baeyer-Villiger/peroxide-assisted decarboxylation, and epoxidation reactions. In conjunction with stopped-flow kinetics, the multifaceted flavin-dependent reaction continuum is physically dissected at molecular level for the first time.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8xw3d695Test

المؤلفون: Lyu, Syue-Yi, Lin, Kuan-Hung, Yeh, Hsien-Wei, Li, Yi-Shan, Huang, Chun-Man, Wang, Yung-Lin, Shih, Hao-Wei, Hsu, Ning-Shian, Wu, Chang-Jer, Li, Tsung-Lin

المصدر: Acta Crystallographica Section D, Structural Biology. 75(10)

مصطلحات موضوعية: Actinobacteria, Alcohol Oxidoreductases, Amycolatopsis, Binding Sites, Cloning, Molecular, Escherichia coli, Flavin Mononucleotide, Kinetics, Mutation, Oxidation-Reduction, Substrate Specificity, electrophilic, nucleophilic duality, alpha-hydroxyacid oxidases, flavin mononucleotide, oxidative decarboxylation, monooxygenase, p-hydroxymandelate oxidase, electrophilic/nucleophilic duality, α-hydroxyacid oxidases, Physical Sciences, Chemical Sciences, Biological Sciences, Biophysics

الوصف: The Y128F single mutant of p-hydroxymandelate oxidase (Hmo) is capable of oxidizing mandelate to benzoate via a four-electron oxidative decarboxylation reaction. When benzoylformate (the product of the first two-electron oxidation) and hydrogen peroxide (an oxidant) were used as substrates the reaction did not proceed, suggesting that free hydrogen peroxide is not the committed oxidant in the second two-electron oxidation. How the flavin mononucleotide (FMN)-dependent four-electron oxidation reaction takes place remains elusive. Structural and biochemical explorations have shed new light on this issue. 15 high-resolution crystal structures of Hmo and its mutants liganded with or without a substrate reveal that oxidized FMN (FMNox) possesses a previously unknown electrophilic/nucleophilic duality. In the Y128F mutant the active-site perturbation ensemble facilitates the polarization of FMNox to a nucleophilic ylide, which is in a position to act on an α-ketoacid, forming an N5-acyl-FMNred dead-end adduct. In four-electron oxidation, an intramolecular disproportionation reaction via an N5-alkanol-FMNred C'α carbanion intermediate may account for the ThDP/PLP/NADPH-independent oxidative decarboxylation reaction. A synthetic 5-deaza-FMNox cofactor in combination with an α-hydroxyamide or α-ketoamide biochemically and structurally supports the proposed mechanism.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5jx70520Test

المؤلفون: Yeh, Hsien-Wei, Lin, Kuan-Hung, Lyu, Syue-Yi, Li, Yi-Shan, Huang, Chun-Man, Wang, Yung-Lin, Shih, Hao-Wei, Hsu, Ning-Shian, Wu, Chang-Jer, Li, Tsung-Lin

المصدر: Acta Crystallographica Section D, Structural Biology. 75(8)

مصطلحات موضوعية: Alcohol Oxidoreductases, Binding Sites, Cloning, Molecular, Crystallography, X-Ray, Decarboxylation, Escherichia coli, Flavin Mononucleotide, Kinetics, Mandelic Acids, Mutagenesis, Site-Directed, Oxidation-Reduction, Protein Binding, Substrate Specificity, mandelate oxidase, flavin mononucleotide, oxidative decarboxylation, hydride transfer, alpha-hydroxyacids, α-hydroxyacids, Physical Sciences, Chemical Sciences, Biological Sciences, Biophysics

الوصف: p-Hydroxymandelate oxidase (Hmo) is a flavin mononucleotide (FMN)-dependent enzyme that oxidizes mandelate to benzoylformate. How the FMN-dependent oxidation is executed by Hmo remains unclear at the molecular level. A continuum of snapshots from crystal structures of Hmo and its mutants in complex with physiological/nonphysiological substrates, products and inhibitors provides a rationale for its substrate enantioselectivity/promiscuity, its active-site geometry/reactivity and its direct hydride-transfer mechanism. A single mutant, Y128F, that extends the two-electron oxidation reaction to a four-electron oxidative decarboxylation reaction was unexpectedly observed. Biochemical and structural approaches, including biochemistry, kinetics, stable isotope labeling and X-ray crystallography, were exploited to reach these conclusions and provide additional insights.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0ts55916Test

المؤلفون: Wang, Yung-Lin, Chang, Chin-Yuan, Hsu, Ning-Shian, Lo, I-Wen, Lin, Kuan-Hung, Chen, Chun-Liang, Chang, Chi-Fon, Wang, Zhe-Chong, Ogasawara, Yasushi, Dairi, Tohru, Maruyama, Chitose, Hamano, Yoshimitsu, Li, Tsung-Lin

المساهمون: Ministry of Science and Technology, Taiwan, Academia Sinica

المصدر: Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N -formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N -formimidoylation or N -iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.

الإتاحة: https://doi.org/10.1038/s41467-023-38218-wTest
https://www.nature.com/articles/s41467-023-38218-w.pdfTest
https://www.nature.com/articles/s41467-023-38218-wTest

المؤلفون: Chen, Chung-I., Lin, Kuan-Hung, Lin, Tzu-Chao, Huang, Meng-Yuan, Chen, Yung-Chih, Huang, Chau-Ching, Wang, Ching-Wen

المصدر: Botanical Studies ; volume 64, issue 1 ; ISSN 1999-3110

مصطلحات موضوعية: Plant Science

الوصف: Background The aim of this study was to determine the actual state of the photosynthetic apparatus and exhibit distinguishable differences in the chlorophyll fluorescence (ChlF) components in different seedling ages of M. oiwakensis plants subjected to different light intensity (LI). Potted 6-month-old greenhouse seedlings and field collected 2.4-year-old seedlings with 5 cm heights were selected and randomly separated into seven groups for photosynthesis measurements illuminated with 50, 100 (assigned as low LI), 300, 500, 1,000 (as moderate LI), 1,500 and 2,000 (as high LI) μmol m –2 s –1 photosynthetic photon flux density (PPFD) treatments. Results n 6-month-old seedlings, as LI increased from 50 to 2,000 PPFD, the values of non-photochemical quenching and photo-inhibitory quenching (qI) increased but potential quantum efficiency of PSII (Fv/Fm) and photochemical efficiency of photosystem II (ΦPSII) values decreased. High electron transport rate and percentage of actual PSII efficiency by Fv/Fm values were observed in 2.4-year-old seedlings at high LI conditions. Furthermore, higher ΦPSII was detected under low LI conditions, with lower energy-dependent quenching (qE) and qI values and photo-inhibition % decreased as well. However, qE and qI increased as ΦPSII decreased and photo-inhibition% increased under high LI treatments. Conclusions These results could be useful for predicting the changes in growth and distribution of Mahonia species grown in controlled environments and open fields with various combinations of varying light illuminations, and ecological monitoring of their restoration and habitat creation is important for provenance conservation and helps to formulate better conservation strategies for the seedlings.

الإتاحة: https://doi.org/10.1186/s40529-023-00369-wTest

المؤلفون: Steinert, Nathaniel D., Jorgenson, Kent W., Lin, Kuan-Hung, Hermanson, Jake B., Lemens, Jake L., Hornberger, Troy A.

المساهمون: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases

المصدر: iScience ; volume 26, issue 4, page 106526 ; ISSN 2589-0042

مصطلحات موضوعية: Multidisciplinary

الإتاحة: https://doi.org/10.1016/j.isci.2023.106526Test
https://api.elsevier.com/content/article/PII:S258900422300603X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S258900422300603X?httpAccept=text/plainTest

المؤلفون: Chen, Cheng-Hsuan, Lin, Kuan-Hung, Chang, Yu-Sen, Chang, Yu-Jie

المساهمون: National Science and Technology Council

المصدر: Process Safety and Environmental Protection ; volume 177, page 1377-1386 ; ISSN 0957-5820

مصطلحات موضوعية: Safety, Risk, Reliability and Quality, General Chemical Engineering, Environmental Chemistry, Environmental Engineering

الإتاحة: https://doi.org/10.1016/j.psep.2023.08.008Test
https://api.elsevier.com/content/article/PII:S0957582023007097?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0957582023007097?httpAccept=text/plainTest