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Article ; Online: Reconstitution of early paclitaxel biosynthetic network.

Liu, Jack Chun-Ting / De La Peña, Ricardo / Tocol, Christian / Sattely, Elizabeth S

2024 Volume 15, Issue 1, Page(s) 1419

Abstract: Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, ... ...

Abstract	Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, we structurally characterize four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression in Nicotiana plants, we observe decreased levels of these proposed byproducts with a concomitant increase in the accumulation of taxadien-5α-ol, the paclitaxel precursor, by three-fold. This enables the reconstitution of a six step biosynthetic pathway, which we further show may function as a metabolic network. Our result demonstrates that six previously characterized Taxus genes can coordinatively produce key paclitaxel intermediates and serves as a crucial platform for the discovery of the remaining biosynthetic genes.
MeSH term(s)	Paclitaxel ; Diterpenes/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Oxidation-Reduction ; Alkenes
Chemical Substances	Paclitaxel (P88XT4IS4D) ; taxa-4(5),11(12)diene ; Diterpenes ; Cytochrome P-450 Enzyme System (9035-51-2) ; Alkenes
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45574-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: How Appropriate Are Recommendations of Online Chat-Based Artificial Intelligence (ChatGPT) to Common Questions on Ventral Hernia Repair?

Lima, Diego Laurentino / Nogueira, Raquel / Liu, Jack / Claus, Christiano / Malcher, Flavio / Sreeramoju, Prashanth / Cavazzola, Leandro Totti

Journal of laparoendoscopic & advanced surgical techniques. Part A

2024 Volume 34, Issue 4, Page(s) 365–367

Abstract: ChatGPT is a conversational AI model developed by OpenAI to generate human-like text based on the input it receives. ChatGPT has become increasingly popular, and the general public may use this tool to ask questions about different medical conditions. ... ...

Abstract	ChatGPT is a conversational AI model developed by OpenAI to generate human-like text based on the input it receives. ChatGPT has become increasingly popular, and the general public may use this tool to ask questions about different medical conditions. There is a lack of data to demonstrate ChatGPT is able to provide reliable information on medical conditions. The aim of our study is to assess the accuracy and appropriateness of ChatGPT answers to questions on ventral hernia management.
MeSH term(s)	Humans ; Artificial Intelligence ; Hernia, Ventral/surgery ; Herniorrhaphy ; Communication
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1381909-4
ISSN	1557-9034 ; 1092-6429
ISSN (online)	1557-9034
ISSN	1092-6429
DOI	10.1089/lap.2023.0475
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Article ; Online: Materials and Applications of 3D Printing Technology in Dentistry: An Overview.

Jeong, Min / Radomski, Kyle / Lopez, Diana / Liu, Jack T / Lee, Jason D / Lee, Sang J

Dentistry journal

2023 Volume 12, Issue 1

Abstract: Purpose: This narrative review aims to provide an overview of the mechanisms of 3D printing, the dental materials relevant to each mechanism, and the possible applications of these materials within different areas of dentistry.: Methods: Subtopics ... ...

Abstract	Purpose: This narrative review aims to provide an overview of the mechanisms of 3D printing, the dental materials relevant to each mechanism, and the possible applications of these materials within different areas of dentistry. Methods: Subtopics within 3D printing technology in dentistry were identified and divided among five reviewers. Electronic searches of the Medline (PubMed) database were performed with the following search keywords: 3D printing, digital light processing, stereolithography, digital dentistry, dental materials, and a combination of the keywords. For this review, only studies or review papers investigating 3D printing technology for dental or medical applications were included. Due to the nature of this review, no formal evidence-based quality assessment was performed, and the search was limited to the English language without further restrictions. Results: A total of 64 articles were included. The significant applications, applied materials, limitations, and future directions of 3D printing technology were reviewed. Subtopics include the chronological evolution of 3D printing technology, the mechanisms of 3D printing technologies along with different printable materials with unique biomechanical properties, and the wide range of applications for 3D printing in dentistry. Conclusions: This review article gives an overview of the history and evolution of 3D printing technology, as well as its associated advantages and disadvantages. Current 3D printing technologies include stereolithography, digital light processing, fused deposition modeling, selective laser sintering/melting, photopolymer jetting, powder binder, and 3D laser bioprinting. The main categories of 3D printing materials are polymers, metals, and ceramics. Despite limitations in printing accuracy and quality, 3D printing technology is now able to offer us a wide variety of potential applications in different fields of dentistry, including prosthodontics, implantology, oral and maxillofacial, orthodontics, endodontics, and periodontics. Understanding the existing spectrum of 3D printing applications in dentistry will serve to further expand its use in the dental field. Three-dimensional printing technology has brought about a paradigm shift in the delivery of clinical care in medicine and dentistry. The clinical use of 3D printing has created versatile applications which streamline our digital workflow. Technological advancements have also paved the way for the integration of new dental materials into dentistry.
Language	English
Publishing date	2023-12-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681351-8
ISSN	2304-6767 ; 2304-6767
ISSN (online)	2304-6767
ISSN	2304-6767
DOI	10.3390/dj12010001
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Article: Reconstitution of Early Paclitaxel Biosynthetic Network.

Chun-Ting Liu, Jack / De La Pena, Ricardo / Tocol, Christian / Sattely, Elizabeth S

bioRxiv : the preprint server for biology

2023

Abstract	Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. This diverts metabolic flux away from the paclitaxel precursor, taxadien-5α-ol, thus previous attempts of reconstitution have not yielded sufficient material for characterization, regardless of the heterologous host. Here, we structurally characterized four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression, levels of these proposed byproducts decrease with a concomitant increase in the accumulation of taxadien-5α-ol by four-fold. This engineered system enabled the reconstitution of a six step biosynthetic pathway to produce isolatable 5α,10β-diacetoxy-taxadien-13α-ol. Furthermore, we showed that this pathway may function as a metabolic network rather than a linear pathway. The engineering of the paclitaxel biosynthetic network demonstrates that
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.27.559859
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Article ; Online: Feasibility of Image Inversion for Ventral Hernia Repair Using the Versius System.

Lima, Diego Laurentino / Pinto, Renato Danesi / Trauczynski, Pedro / Liu, Jack / Cavazzola, Leandro Totti

Journal of laparoendoscopic & advanced surgical techniques. Part A

2023 Volume 34, Issue 2, Page(s) 144–146

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Humans ; Feasibility Studies ; Hernia, Ventral/surgery ; Robotics ; Herniorrhaphy/methods ; Surgeons ; Robotic Surgical Procedures/methods
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1381909-4
ISSN	1557-9034 ; 1092-6429
ISSN (online)	1557-9034
ISSN	1092-6429
DOI	10.1089/lap.2023.0404
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Article: Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling.

Zhang, Jisheng / Wu, Keheng / Liu, Bo / Hou, Shuguang / Li, Xue / Ye, Xiang / Liu, Jack / He, Qing

Frontiers in medicine

2023 Volume 10, Page(s) 1056318

Abstract: Aims: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of ... ...

Abstract	Aims: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characteristics and bioequivalence of ipratropium bromide (IB) inhalation aerosol, reference and test products in healthy Chinese subjects; (2) to establish a physiologically based pharmacokinetic (PBPK) model and verify the accuracy of the model in predicting bioequivalence; (3) attempt to use the model to predict the regional distribution of particles in the lung after inhalation, and discuss the effect of gastrointestinal drug absorption of IB on systemic exposure. Methods: The study involved two clinical studies. Clinical study-1 (registration number: CTR20201284) was used with non-clinical data to construct and validate a PBPK model in the B Results: The established PBPK model successfully simulated the Conclusion: This model provided a reliable method for exploring the correlation between
Language	English
Publishing date	2023-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1056318
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Book: Integrating landscape ecology into natural resource management

Liu, Jianguo

(Studies in landscape ecology)

2002

Author's details	ed. by Jianguo Liu
Series title	Studies in landscape ecology
Keywords	Landscape ecology ; Natural resources ; Angewandte Landschaftsökologie
Subject code	333.7
Language	English
Size	XX, 480 S., [8] Bl. : Ill., graph. Darst., Kt., 25 cm
Publisher	Cambridge Univ. Press
Publishing place	Cambridge u.a.
Publishing country	Great Britain
Document type	Book
Note	Includes bibliographical references and index
HBZ-ID	HT013440801
ISBN	0-521-78015-2 ; 0-521-78433-6 ; 978-0-521-78015-5 ; 978-0-521-78433-7
Database	Catalogue ZB MED Nutrition, Environment, Agriculture

In stock of ZB MED Bonn / Germany

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028/722	available for loan (reading room)	Freihandmagazin (U1)

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Article: Predicting pharmacodynamic effects through early drug discovery with artificial intelligence-physiologically based pharmacokinetic (AI-PBPK) modelling.

Wu, Keheng / Li, Xue / Zhou, Zhou / Zhao, Youni / Su, Mei / Cheng, Zhuo / Wu, Xinyi / Huang, Zhijun / Jin, Xiong / Li, Jingxi / Zhang, Mengjun / Liu, Jack / Liu, Bo

Frontiers in pharmacology

2024 Volume 15, Page(s) 1330855

Abstract: A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model links the concentration-time profile of a drug with its therapeutic effects based on the underlying biological or physiological processes. Clinical endpoints play a pivotal role in drug ... ...

Abstract	A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model links the concentration-time profile of a drug with its therapeutic effects based on the underlying biological or physiological processes. Clinical endpoints play a pivotal role in drug development. Despite the substantial time and effort invested in screening drugs for favourable pharmacokinetic (PK) properties, they may not consistently yield optimal clinical outcomes. Furthermore, in the virtual compound screening phase, researchers cannot observe clinical outcomes in humans directly. These uncertainties prolong the process of drug development. As incorporation of Artificial Intelligence (AI) into the physiologically based pharmacokinetic/pharmacodynamic (PBPK) model can assist in forecasting pharmacodynamic (PD) effects within the human body, we introduce a methodology for utilizing the AI-PBPK platform to predict the PK and PD outcomes of target compounds in the early drug discovery stage. In this integrated platform, machine learning is used to predict the parameters for the model, and the mechanism-based PD model is used to predict the PD outcome through the PK results. This platform enables researchers to align the PK profile of a drug with desired PD effects at the early drug discovery stage. Case studies are presented to assess and compare five potassium-competitive acid blocker (P-CAB) compounds, after calibration and verification using vonoprazan and revaprazan.
Language	English
Publishing date	2024-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2024.1330855
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Article ; Online: Predicting Drug-Drug Interactions Involving Rifampicin Using a Semi-mechanistic Hepatic Compartmental Model.

Li, Jingxi / Li, Xue / Wu, Keheng / Long, Sihui / Zhao, Youni / Jin, Xiong / Zhang, Mengjun / Wu, Xinyi / Huang, Zhijun / Zhou, Zhou / Liu, Jack / Liu, Bo

Pharmaceutical research

2024 Volume 41, Issue 4, Page(s) 699–709

Abstract: Aims: To develop a semi-mechanistic hepatic compartmental model to predict the effects of rifampicin, a known inducer of CYP3A4 enzyme, on the metabolism of five drugs, in the hope of informing dose adjustments to avoid potential drug-drug interactions.! ...

Abstract	Aims: To develop a semi-mechanistic hepatic compartmental model to predict the effects of rifampicin, a known inducer of CYP3A4 enzyme, on the metabolism of five drugs, in the hope of informing dose adjustments to avoid potential drug-drug interactions. Methods: A search was conducted for DDI studies on the interactions between rifampicin and CYP substrates that met specific criteria, including the availability of plasma concentration-time profiles, physical and absorption parameters, pharmacokinetic parameters, and the use of healthy subjects at therapeutic doses. The semi-mechanistic model utilized in this study was improved from its predecessors, incorporating additional parameters such as population data (specifically for Chinese and Caucasians), virtual individuals, gender distribution, age range, dosing time points, and coefficients of variation. Results: Optimal parameters were identified for our semi-mechanistic model by validating it with clinical data, resulting in a maximum difference of approximately 2-fold between simulated and observed values. PK data of healthy subjects were used for most CYP3A4 substrates, except for gilteritinib, which showed no significant difference between patients and healthy subjects. Dose adjustment of gilteritinib co-administered with rifampicin required a 3-fold increase of the initial dose, while other substrates were further tuned to achieve the desired drug exposure. Conclusions: The pharmacokinetic parameters AUCR and CmaxR of drugs metabolized by CYP3A4, when influenced by Rifampicin, were predicted by the semi-mechanistic model to be approximately twice the empirically observed values, which suggests that the semi-mechanistic model was able to reasonably simulate the effect. The doses of four drugs adjusted via simulation to reduce rifampicin interaction.
MeSH term(s)	Humans ; Rifampin/pharmacokinetics ; Cytochrome P-450 CYP3A/metabolism ; Epidemiological Models ; Drug Interactions ; Models, Biological ; Aniline Compounds ; Pyrazines
Chemical Substances	Rifampin (VJT6J7R4TR) ; gilteritinib (66D92MGC8M) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Aniline Compounds ; Pyrazines
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-024-03691-5
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Article ; Online: The significance of response shift in sinus surgery outcomes.

Liu, Jack J / Davis, Greg E

International forum of allergy & rhinology

2014 Volume 5, Issue 1, Page(s) 55–59

Abstract: Background: Functional endoscopic sinus surgery (FESS) aims to improve quality-of-life (QOL). Perception of QOL can change according to one's current medical or emotional state. This is known as response shift. It can be measured by the "then-test," ... ...

Abstract	Background: Functional endoscopic sinus surgery (FESS) aims to improve quality-of-life (QOL). Perception of QOL can change according to one's current medical or emotional state. This is known as response shift. It can be measured by the "then-test," which asks patients to report pretreatment symptoms after receiving treatment. Patients often do not understand their disease burden until their symptoms are improved. This study aims to assess the significance of response shift in FESS outcomes. Methods: This was a prospective cohort study that included chronic rhinosinusitis patients from 2010 to 2012 who completed a preoperative 20-item Sino-Nasal Outcome Test (SNOT-20). Two SNOT-20 forms were mailed approximately 6 months after surgery. Patients completed 1 SNOT-20 according to their preoperative symptoms in light of their current state of health ("then-test") and the other based on postoperative symptoms. The preoperative and postoperative SNOT-20 difference represented the treatment effect and the preoperative SNOT-20 and then-test difference represented the response shift. Results: Thirty-two completed responses were obtained. Using a 0 to 5 scale, mean treatment effect was -0.96 (p < 0.01), which signifies a QOL improvement. Mean response shift was +0.42 (p = 0.01). This positive value signifies that patients felt they were worse off preoperatively, likely due to a positive change in health status. The actual treatment effect is the sum of the measured treatment effect and response shift, which was -1.38. Conclusion: Response shift exists and can be quantified. The actual treatment effect was more profound when response shift was included. Therefore, future studies should account for this often unmeasured, potential change in QOL.
MeSH term(s)	Adolescent ; Adult ; Chronic Disease ; Cohort Studies ; Emotions ; Endoscopy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Paranasal Sinuses/surgery ; Perception ; Postoperative Period ; Prospective Studies ; Quality of Life ; Research Design ; Rhinitis/diagnosis ; Rhinitis/psychology ; Sinusitis/diagnosis ; Sinusitis/psychology ; Surveys and Questionnaires ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2014-10-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2625826-2
ISSN	2042-6984 ; 2042-6976
ISSN (online)	2042-6984
ISSN	2042-6976
DOI	10.1002/alr.21420
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