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  1. AU="Tan, Jiacheng"
  2. AU="Weiss, Jonathan D"

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  1. Article ; Online: Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment.

    Fine, Justyn / Meksiriporn, Bunyarit / Tan, Jiacheng / Spangler, Jamie B

    Annual review of chemical and biomolecular engineering

    2024  

    Abstract: Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility ... ...

    Abstract Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility of antibody therapies, significant efforts have been invested in designing multispecific antibodies, which engage multiple targets using a single molecule. These efforts have culminated in remarkable translational progress, including nine US Food and Drug Administration-approved multispecific antibodies, with countless others in various stages of preclinical or clinical development. In this review, we discuss several categories of multispecific antibodies that have achieved clinical approval or shown promise in earlier stages of development. We focus on the molecular mechanisms used by multispecific antibodies and how these mechanisms inform their customized design and formulation. In particular, we discuss multispecific antibodies that target multiple disease markers, multiparatopic antibodies, and immune-interfacing antibodies. Overall, these innovative multispecific antibody designs are fueling exciting advances across the immunotherapeutic landscape. Expected final online publication date for the
    Language English
    Publishing date 2024-01-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2516755-8
    ISSN 1947-5446 ; 1947-5438
    ISSN (online) 1947-5446
    ISSN 1947-5438
    DOI 10.1146/annurev-chembioeng-100522-102155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A New Method for Inversion of Dam Foundation Hydraulic Conductivity Using an Improved Genetic Algorithm Coupled with an Unsaturated Equivalent Continuum Model and Its Application.

    Peng, Jiayi / Shen, Zhenzhong / Xu, Liqun / Gan, Lei / Tan, Jiacheng

    Materials (Basel, Switzerland)

    2023  Volume 16, Issue 4

    Abstract: Seepage is a main cause of dam failure, and its stability analysis is the focus of a dam's design, construction, and management. Because a geological survey can only determine the range of a dam foundation's hydraulic conductivity, hydraulic conductivity ...

    Abstract Seepage is a main cause of dam failure, and its stability analysis is the focus of a dam's design, construction, and management. Because a geological survey can only determine the range of a dam foundation's hydraulic conductivity, hydraulic conductivity inversion is crucial in engineering. However, current inversion methods of dam hydraulic conductivity are either not accurate enough or too complex to be directly used in engineering. Therefore, this paper proposes a new method for the inversion of hydraulic conductivity with high application value in hydraulic engineering using an improved genetic algorithm coupled with an unsaturated equivalent continuum model (IGA-UECM). This method is implemented by a new code that fully considers engineering applicability. In addition to overcoming the premature convergence shortcomings of traditional genetic algorithms, it converges faster than Bayesian optimization and tree-structured Parzen estimator inversion algorithms. This method is verified by comparing the water head from drilling exploration and inversion. The results of the inversion are used to study the influence of a cement grouting curtain layout scheme on the seepage field of the Hami concrete-face rockfill dam in China, which is used as an engineering application case of the IGA-UECM. The law of the seepage field is reasonable, which verifies the validity of the IGA-UECM. The new inversion method of hydraulic conductivity and the proposed cement grouting curtain layout in this study offer possible strategies for the design, construction, and management of concrete-face rockfill dams.
    Language English
    Publishing date 2023-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2487261-1
    ISSN 1996-1944
    ISSN 1996-1944
    DOI 10.3390/ma16041662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Experimental Investigation on Seepage Characteristics of Clay-Structure Interface after Shear Deformation.

    Tan, Jiacheng / Shen, Zhenzhong / Xu, Liqun / Zhang, Hongwei / He, Yingming

    Materials (Basel, Switzerland)

    2022  Volume 15, Issue 11

    Abstract: There exist shear and seepage behaviors on the interface between clay core and concrete slab in clay core dams. In order to investigate the seepage characteristics of the clay-structure interface after shear deformation, a shear-seepage test system is ... ...

    Abstract There exist shear and seepage behaviors on the interface between clay core and concrete slab in clay core dams. In order to investigate the seepage characteristics of the clay-structure interface after shear deformation, a shear-seepage test system is proposed, in which the seepage direction is perpendicular to the shear direction. The shear test and shear-seepage test are performed on clay-metal and clay-mortar interfaces under different normal stresses (100, 200, 400, 800, and 1600 kPa). The shear stress-deformation curves of two clay-structure interfaces exhibit softening behavior and residual friction behavior. The interface roughness can enhance peak and residual shear strength and increase peak displacement. The shear-seepage test results show that specimen permeability decreases first and then increases to a stable value as shear deformation increases under low normal stress, while it decreases continuously and then retains stability under high normal stress. The interface roughness enhances specimen permeability under low normal stress, whereas it has a weak effect on specimen permeability under high normal stress. Compared with initial permeability, shear deformation reduces specimen permeability rather than raise it. The ratio of stabilized permeability coefficient to initial value ranges from 0.6 to 0.8. The clay-structure interface still has a good resistance to seepage failure after shear deformation. The shear dilation features and interface pore decrease caused by shear behavior are the internal attributions of clay-structure specimen permeability evolution.
    Language English
    Publishing date 2022-05-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2487261-1
    ISSN 1996-1944
    ISSN 1996-1944
    DOI 10.3390/ma15113802
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Antibacterial Nanocellulose-TiO

    Tan, Jiacheng / Deng, Hangjun / Lu, Fangfang / Chen, Wei / Su, Xiuping / Wang, Hairong

    Polymers

    2023  Volume 15, Issue 22

    Abstract: In this paper, we report an antibacterial, recyclable nanocellulose-titanium dioxide/polyester nonwoven fabric (NC- ... ...

    Abstract In this paper, we report an antibacterial, recyclable nanocellulose-titanium dioxide/polyester nonwoven fabric (NC-TiO
    Language English
    Publishing date 2023-11-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527146-5
    ISSN 2073-4360 ; 2073-4360
    ISSN (online) 2073-4360
    ISSN 2073-4360
    DOI 10.3390/polym15224376
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Design, synthesis, and pharmacological evaluation of novel benzothiazole derivatives targeting LCK in acute lymphoblastic leukemia.

    Chen, Yanmei / Zhang, Kai / Tan, Jiacheng / Fan, Zhichao / Fu, Yuqi / Li, Xiang / Liu, Bo / Wang, Guan

    Bioorganic chemistry

    2024  Volume 144, Page(s) 107180

    Abstract: Lymphocyte-specific protein tyrosine kinase (LCK), a member of the Src family of tyrosine kinases, is implicated in the pathogenesis of almost all types of leukemia via T cells activation and signal transduction. LCK is highly expressed in acute ... ...

    Abstract Lymphocyte-specific protein tyrosine kinase (LCK), a member of the Src family of tyrosine kinases, is implicated in the pathogenesis of almost all types of leukemia via T cells activation and signal transduction. LCK is highly expressed in acute lymphoblastic leukemia (ALL), and knockdown of the LCK gene can significantly inhibit the proliferation of leukemia cell lines. Here, we designed and synthesized a series of benzothiazole derivatives as novel LCK inhibitors using both docking-based virtual screening and activity assays for structural optimization. Among these compounds, 7 m showed a strong inhibitory activity in the proliferation of leukemia cell lines and LCK kinase activity. Moreover, we found that compound 7 m could induce apoptosis while simultaneously blocking cell cycle via decreasing its phosphorylation at Tyr394 of the LCK. Collectively, these findings shed new light on compound 7 m that would be utilized as a promising drug candidate with apoptosis-triggered and cell cycle arrest activities for the future ALL therapy.
    MeSH term(s) Humans ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism ; Phosphorylation ; Signal Transduction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Benzothiazoles/pharmacology
    Chemical Substances Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (EC 2.7.10.2) ; Benzothiazoles
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120080-x
    ISSN 1090-2120 ; 0045-2068
    ISSN (online) 1090-2120
    ISSN 0045-2068
    DOI 10.1016/j.bioorg.2024.107180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4207: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Comparison of 180° anti-reflux mucosectomy versus 270° anti-reflux mucosectomy for treatment of refractory gastroesophageal reflux disease: a retrospective study.

    Yang, Xinyi / Tan, Jiacheng / Liu, Yang / Feng, Yadong / Shi, Ruihua

    Surgical endoscopy

    2021  Volume 36, Issue 7, Page(s) 5002–5010

    Abstract: Background: Anti-reflux mucosectomy (ARMS) is a novel endoscopic treatment for refractory gastroesophageal reflux disease (rGERD). Several studies have validated its safety and effectiveness, but postoperative dysphagia remains in concern. Since the ... ...

    Abstract Background: Anti-reflux mucosectomy (ARMS) is a novel endoscopic treatment for refractory gastroesophageal reflux disease (rGERD). Several studies have validated its safety and effectiveness, but postoperative dysphagia remains in concern. Since the influence of different resection ranges on efficacy and complications of ARMS has rarely been studied, this study aimed to compare outcomes of 180°ARMS and 270°ARMS in treatment of rGERD.
    Methods: This study was conducted from August 2017 to September 2020. 39 eligible patients underwent either 180° ARMS or 270° ARMS and followed up at 6 months postoperation. Primary outcome measure was assessed by Gastroesophageal Reflux Disease Questionnaire (GERD-Q). Secondary outcomes included quality of life, PPI use, gastroesophageal flap valve grade, presence of reflux esophagitis, acid exposure time (AET), distal contractile integral (DCI), and integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) and complication rate. Per-protocol analysis was performed.
    Results: Among 39 patients, 18 underwent 180° ARMS, while 21 underwent 270° ARMS. At postoperative 6 months follow-up period, primary outcome showed no significant difference between two groups (p = 0.34). Similarly, no significant difference was demonstrated between groups regarding most secondary outcomes except for fewer complaints of newly dysphagia in 180° ARMS group. No other serious complications were observed in both groups.
    Conclusion: Although 180° ARMS and 270° ARMS could be equally effective for treatment of rGERD, 180° ARMS might be more recommended due to lower incidence of newly post-procedural dysphagia.
    MeSH term(s) Deglutition Disorders/etiology ; Esophagitis, Peptic ; Gastroesophageal Reflux/surgery ; Humans ; Manometry/methods ; Quality of Life ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2021-11-15
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639039-0
    ISSN 1432-2218 ; 0930-2794
    ISSN (online) 1432-2218
    ISSN 0930-2794
    DOI 10.1007/s00464-021-08857-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2214: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Diverse N-Substituted Azole-Containing Amino Acids as Building Blocks for Cyclopeptides.

    Motevalli, Somayeh / Nguyen, Michelle T / Tan, Jiacheng / Fuller, Amelia A

    ACS omega

    2020  Volume 5, Issue 2, Page(s) 1214–1220

    Abstract: The preparation of 16 oxazole- or thiazole-containing amino esters bearing a wide array of N-substitution is reported. These were accessed in 40-92% yield via an ... ...

    Abstract The preparation of 16 oxazole- or thiazole-containing amino esters bearing a wide array of N-substitution is reported. These were accessed in 40-92% yield via an AgClO
    Language English
    Publishing date 2020-01-08
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.9b03682
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: In situ

    Chen, Wei / Feng, Xiaolin / Zhang, Danyin / Lu, Fangfang / Wang, Hairong / Tan, Jiacheng / Xu, Qiao / Liu, Yongkun / Cao, Zhihai / Su, Xiuping

    RSC advances

    2022  Volume 12, Issue 31, Page(s) 19974–19980

    Abstract: A cotton fabric/titanium dioxide-nanocellulose ( ... ...

    Abstract A cotton fabric/titanium dioxide-nanocellulose (TiO
    Language English
    Publishing date 2022-07-08
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d2ra00992g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: In situ synthesis of TiO₂/NC on cotton fibers with antibacterial properties and recyclable photocatalytic degradation of dyes

    Chen, Wei / Feng, Xiaolin / Zhang, Danyin / Lu, Fangfang / Wang, Hairong / Tan, Jiacheng / Xu, Qiao / Liu, Yongkun / Cao, Zhihai / Su, Xiuping

    RSC advances. 2022 July 08, v. 12, no. 31

    2022  

    Abstract: A cotton fabric/titanium dioxide-nanocellulose (TiO₂-Cot.) flexible and recyclable composite material with highly photocatalytic degradation of dyes and antibacterial properties was synthesized. During the preparation process, nano-TiO₂ particles were ... ...

    Abstract A cotton fabric/titanium dioxide-nanocellulose (TiO₂-Cot.) flexible and recyclable composite material with highly photocatalytic degradation of dyes and antibacterial properties was synthesized. During the preparation process, nano-TiO₂ particles were synthesized through an in situ strategy and grown on cotton fiber, and were wrapped with cellulose nanocrystals (NC). The prepared TiO₂-Cot. was characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The SEM and EDS results showed that nano-TiO₂ particles were evenly distributed on the fiber surface. The prepared TiO₂@Cot. has excellent photocatalytic efficiency of 95.68% for MB and 92.77% for AR under weak ultraviolet irradiation over 6 h. At the same time, it has excellent antibacterial activity against S. aureus and E. coli. The stability and reusability of the materials were also investigated.
    Keywords Escherichia coli ; Fourier transform infrared spectroscopy ; X-ray diffraction ; antibacterial properties ; cellulose ; composite materials ; cotton fabric ; lint cotton ; nanocrystals ; photocatalysis ; titanium ; ultraviolet radiation
    Language English
    Dates of publication 2022-0708
    Size p. 19974-19980.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/d2ra00992g
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

    Ludwig, Seth D / Meksiriporn, Bunyarit / Tan, Jiacheng / Kureshi, Rakeeb / Mishra, Akhilesh / Kaeo, Kyle J / Zhu, Angela / Stavrakis, Georgia / Lee, Stephen J / Schodt, David J / Wester, Michael J / Kumar, Dhiraj / Lidke, Keith A / Cox, Andrea L / Dooley, Helen M / Nimmagadda, Sridhar / Spangler, Jamie B

    Cell chemical biology

    2024  Volume 31, Issue 5, Page(s) 904–919.e11

    Abstract: Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment ... ...

    Abstract Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.
    MeSH term(s) B7-H1 Antigen/metabolism ; B7-H1 Antigen/immunology ; B7-H1 Antigen/antagonists & inhibitors ; Animals ; Mice ; Humans ; Down-Regulation/drug effects ; Mice, Inbred C57BL ; Female ; Cell Line, Tumor ; Tumor Microenvironment/immunology ; Tumor Microenvironment/drug effects
    Chemical Substances CD274 protein, human
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 2451-9448
    ISSN (online) 2451-9448
    DOI 10.1016/j.chembiol.2024.02.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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