Browsing by Author "Li, Zhigang"

Now showing 1 - 7 of 7
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    Fabrication and use of silicon hollow-needle arrays to achieve tissue nanotransfection in mouse tissue in vivo
    (Springer Nature, 2021) Xuan, Yi; Ghatak, Subhadip; Clark, Andrew; Li, Zhigang; Khanna, Savita; Pak, Dongmin; Agarwal, Mangilal; Roy, Sashwati; Duda, Peter; Sen, Chandan K.; Surgery, School of Medicine
    Tissue nanotransfection (TNT) is an electromotive gene transfer technology that was developed to achieve tissue reprogramming in vivo. This protocol describes how to fabricate the required hardware, commonly referred to as a TNT chip, and use it for in vivo TNT. Silicon hollow-needle arrays for TNT applications are fabricated in a standardized and reproducible way. In <1 s, these silicon hollow-needle arrays can be used to deliver plasmids to a predetermined specific depth in murine skin in response to pulsed nanoporation. Tissue nanotransfection eliminates the need to use viral vectors, minimizing the risk of genomic integration or cell transformation. The TNT chip fabrication process typically takes 5-6 d, and in vivo TNT takes 30 min. This protocol does not require specific expertise beyond a clean room equipped for basic nanofabrication processes.
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    Head impact accelerations for brain strain-related responses in contact sports: a model-based investigation
    (Springer, 2014-10) Ji, Songbai; Zhao, Wei; Li, Zhigang; McAllister, Thomas W.; Psychiatry, School of Medicine
    Both linear (alin) and rotational (arot) accelerations contribute to head impacts on the field in contact sports; however, they are often isolated in injury studies. It is critical to evaluate the feasibility of estimating brain responses using isolated instead of full degrees-of-freedom (DOFs) accelerations. In this study, we investigated the sensitivities of regional brain strain-related responses to resultant alin and arot as well as the relative contributions of these acceleration components to the responses via random sampling and linear regression using parameterized, triangulated head impacts with kinematic variable values based on on-field measurements. Two independently established and validated finite element models of the human head were employed to evaluate model consistency and dependency in results: the Dartmouth Head Injury Model (DHIM) and Simulated Injury Monitor (SIMon). For the majority of the brain, volume-weighted regional peak strain, strain rate, and von Mises stress accumulated from the simulation significantly correlated to the product of the magnitude and duration of arot, or effectively, the rotational velocity, but not to alin. Responses from arot-only were comparable to the full-DOFs counterparts especially when normalized by injury-causing thresholds (e.g., volume fractions of large differences virtually diminished (i.e., <1%) at typical difference percentage levels of 1–4% on average). These model-consistent results support the inclusion of both rotational acceleration magnitude and duration into kinematics-based injury metrics, and demonstrate the feasibility of estimating strain-related responses from isolated arot for analyses of strain-induced injury relevant to contact sports without significant loss of accuracy, especially for the cerebrum.
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    Mechanistic examination of causes for narrow distribution in an endangered shrub: a comparison of its responses to drought stress with a widespread congeneric species
    (Springer, 2016-12) Cui, Hongxia; Cong, Shuhua; Wang, Xianzhong; Hao, Haiping; Shi, Lei; Zhang, Huijin; Li, Zhigang; Hu, Tianhua; Qin, Yongsheng; Department of Biology, School of Science
    Although deep rooting is usually considered a drought-tolerant trait, we found that Syringapinnatifolia, a deep rooting and hydrotropic shrub, has a limited distribution in arid areas. To elucidate the mechanisms for its narrow distribution, we conducted two experiments to examine the physiological and morphological responses to water availability and heterogeneity in S. pinnatifolia and a widespread congeneric species, S. oblata. We measured gas exchange, water use efficiency, and plasticity index in plants of these two species grown at different levels of soil water regimes and in containers with patched water distribution. Our results showed that high photosynthetic capacity in the narrowly distributed S. pinnatifolia was an important factor enabling its survival in the harsh sub-alpine environment. High photosynthetic capacity in S. pinnatifolia, however, was obtained at the expense of high transpiratory water loss, resulting in lower integrative water use efficiency. Biomass allocation to roots in S. pinnatifolia increased by 73 % when soil water increased from 75 to 95 % field capacity, suggesting that S. pinnatifolia could be less competitive for above-ground resources under favorable water regimes. The horizontal root hydrotropism and vertical root hydrotropism of S. pinnatifolia in soil with patched water patterns were likely related to compensation for leaf water loss at low soil water level, indicating a limited capacity for homeostasis within the plant for water conservation and lower level of inherent drought-tolerance. In summary, greater degree of morphological plasticity but lower degree of physiological adjustment may be the main causes for the hydrotropism and narrow distribution of S. pinnatifolia in the sub-alpine habitats.
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    Modeling the gene delivery process of the needle array-based tissue nanotransfection
    (Springer, 2022) Li, Zhigang; Xuan, Yi; Ghatak, Subhadip; Guda, Poornachander R.; Roy, Sashwati; Sen, Chandan K.; Surgery, School of Medicine
    Hollow needle array-based tissue nanotransfection (TNT) presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric pulses. In this work, the gene delivery process of TNT was simulated and experimentally validated. We adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin structure. The distribution of nonuniform electric field across the skin results in various electroporation behavior for each cell. Cells underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric field. The percentage of electroporated cells within the skin structure, with pore radius over 10 nm, increases from 25% to 82% as the applied voltage increases from 100 to 150 V/mm. Furthermore, the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based model. The delivery distance increased nonlinearly as the applied voltage and pulse number increased, which mainly depends on the diffusion characteristics and electric conductivity of each layer. It was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery depth. This work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings.
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    MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants
    (Oxford University Press, 2024) Jin, Weijia; Xia, Yi; Nizomov, Javlon; Liu, Yunlong; Li, Zhigang; Lu, Qing; Chen, Li; Medical and Molecular Genetics, School of Medicine
    Summary: Massively parallel reporter assay (MPRA) is an important technology for evaluating the impact of genetic variants on gene regulation. Here, we present MPRAVarDB, an online database and web server for exploring regulatory effects of genetic variants. MPRAVarDB harbors 18 MPRA experiments designed to assess the regulatory effects of genetic variants associated with GWAS loci, eQTLs, and genomic features, totaling 242 818 variants tested more than 30 cell lines and 30 human diseases or traits. MPRAVarDB enables users to query MPRA variants by genomic region, disease and cell line, or any combination of these parameters. Notably, MPRAVarDB offers a suite of pretrained machine-learning models tailored to the specific disease and cell line, facilitating the prediction of regulatory variants. The user-friendly interface allows users to receive query and prediction results with just a few clicks. Availability and implementation: https://mpravardb.rc.ufl.edu.
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    MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants
    (bioRxiv, 2024-04-03) Nizomov, Javlon; Jin, Weijia; Xia, Yi; Liu, Yunlong; Li, Zhigang; Chen, Li; Medical and Molecular Genetics, School of Medicine
    Massively parallel reporter assay (MPRA) is an important technology to evaluate the impact of genetic variants on gene regulation. Here, we present MPRAVarDB, an online database and web server, for exploring regulatory effects of genetic variants. MPRAVarDB harbors 18 MPRA experiments designed to assess the regulatory effects of genetic variants associated with GWAS loci, eQTLs and various genomic features, resulting in a total of 242,818 variants tested across more than 30 cell lines and 30 human diseases or traits. MPRAVarDB empowers the query of MPRA variants by genomic region, disease and cell line or by any combination of these query terms. Notably, MPRAVarDB offers a suite of pretrained machine learning models tailored to the specific disease and cell line, facilitating the genome-wide prediction of regulatory variants. MPRAVarDB is friendly to use, and users only need a few clicks to receive query and prediction results.
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    The value of enhanced CT scanning for predicting lymph node metastasis along the right recurrent laryngeal nerve in esophageal squamous cell carcinoma
    (AME, 2020-12) Li, Bin; Li, Baiwei; Jiang, Haoyao; Yang, Yang; Zhang, Xiaobin; Su, Yuchen; Hua, Rong; Gu, Haiyong; Guo, Xufeng; Ye, Bo; Yang, Yu; He, Yi; Sun, Yifeng; Piessen, Guillaume; Hochwald, Steven N.; Cuesta, Miguel A.; Birdas, Thomas J.; Li, Zhigang; Surgery, School of Medicine
    Background: The right recurrent laryngeal nerve (RRLN) is the region most prone to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Nodal involvement may be underestimated by traditional imaging prediction criteria, such as a short axis diameter of 10 mm. The purpose of this study was to determine a more accurate imaging criterion to guide clinical treatment strategy selection. Methods: The clinical data of 307 patients with thoracic ESCC who underwent surgery at Shanghai Chest Hospital between January 2018 and December 2018 were retrospectively analyzed. Utilizing 1-mm layer thickness enhanced computed tomography (CT), the RRLN lymph node short diameter (LNSD) size was measured. Univariate and multivariate analyses were performed to determine the risk factors for lymph node metastasis along the RRLN. Results: In our study, RRLN lymph node metastasis occurred in 60 (19.5%) patients and general lymph node metastasis occurred in 150 (48.9%) patients. Of the resected lymph nodes along the RRLN, 14.5% (121/832) were positive. Multivariate analysis identified LNSD [odds ratio (OR), 1.236] as an independent risk factor for RRLN lymph node metastasis. In CT evaluation, a short diameter of 6.5 mm in the RRLN lymph nodes is a critical predictor of metastasis at this site (sensitivity =50%, specificity =83.4%) and a larger short diameter was associated with a higher risk of metastasis (P<0.001). Conclusions: A 6.5 mm cutoff in LNSD can be applied to clinically predict lymph node metastasis in the RRLN region for patients with ESCC.