Browsing by Author "Wang, Pei"

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    Multi-region Whole Exome Sequencing of Intraductal Papillary Mucinous Neoplasms Reveals Frequent Somatic KLF4 Mutations Predominantly in Low-Grade Regions
    (BMJ, 2021) Fujikura, Kohei; Hosoda, Waki; Felsenstein, Matthäus; Song, Qianqian; Reiter, Johannes G.; Zheng, Lily; Guthrie, Violeta Beleva; Rincon, Natalia; Molin, Marco Dal; Dudley, Jonathan; Cohen, Joshua D.; Wang, Pei; Fischer, Catherine G.; Braxton, Alicia M.; Noë, Michaël; Jongepier, Martine; Castillo, Carlos Fernández-del; Mino-Kenudson, Mari; Schmidt, C. Max; Yip-Schneider, Michele T.; Lawlor, Rita T.; Salvia, Roberto; Roberts, Nicholas J.; Thompson, Elizabeth D.; Karchin, Rachel; Lennon, Anne Marie; Jiao, Yuchen; Wood, Laura D.; Surgery, School of Medicine
    Objective: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions that can progress to invasive pancreatic cancer and are classified as low-grade or high-grade based on the morphology of the neoplastic epithelium. We aimed to compare genetic alterations in low-grade and high-grade regions of the same IPMN in order to identify molecular alterations underlying neoplastic progression. Design: We performed multiregion whole exome sequencing on tissue samples from 17 IPMNs with both low-grade and high-grade dysplasia (76 IPMN regions, including 49 from low-grade dysplasia and 27 from high-grade dysplasia). We reconstructed the phylogeny for each case, and we assessed mutations in a novel driver gene in an independent cohort of 63 IPMN cyst fluid samples. Results: Our multiregion whole exome sequencing identified KLF4, a previously unreported genetic driver of IPMN tumorigenesis, with hotspot mutations in one of two codons identified in >50% of the analyzed IPMNs. Mutations in KLF4 were significantly more prevalent in low-grade regions in our sequenced cases. Phylogenetic analyses of whole exome sequencing data demonstrated diverse patterns of IPMN initiation and progression. Hotspot mutations in KLF4 were also identified in an independent cohort of IPMN cyst fluid samples, again with a significantly higher prevalence in low-grade IPMNs. Conclusion: Hotspot mutations in KLF4 occur at high prevalence in IPMNs. Unique among pancreatic driver genes, KLF4 mutations are enriched in low-grade IPMNs. These data highlight distinct molecular features of low-grade and high-grade dysplasia and suggest diverse pathways to high-grade dysplasia via the IPMN pathway.
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    Neuroprotective effects of interleukin 10 in spinal cord injury
    (Frontiers Media, 2023-07-10) Li, Juan; Wang, Pei; Zhou, Ting; Jiang, Wenwen; Wu, Hang; Zhang, Shengqi; Deng, Lingxiao; Wang, Hongxing; Neurological Surgery, School of Medicine
    Spinal cord injury (SCI) starts with a mechanical and/or bio-chemical insult, followed by a secondary phase, leading progressively to severe collapse of the nerve tissue. Compared to the peripheral nervous system, injured spinal cord is characterized by weak axonal regeneration, which leaves most patients impaired or paralyzed throughout lifetime. Therefore, confining, alleviating, or reducing the expansion of secondary injuries and promoting functional connections between rostral and caudal regions of lesion are the main goals of SCI therapy. Interleukin 10 (IL-10), as a pivotal anti-inflammatory and immunomodulatory cytokine, exerts a wide spectrum of positive effects in the treatment of SCI. The mechanisms underlying therapeutic effects mainly include anti-oxidative stress, limiting excessive inflammation, anti-apoptosis, antinociceptive effects, etc. Furthermore, IL-10 displays synergistic effects when combined with cell transplantation or neurotrophic factor, enhancing treatment outcomes. This review lists pleiotropic mechanisms underlying IL-10-mediated neuroprotection after SCI, which may offer fresh perspectives for clinical translation.
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    Quantifying the Controls on Evapotranspiration Partitioning in the Highest Alpine Meadow Ecosystem
    (AGU, 2020-04) Cui, Jiangpeng; Tian, Lide; Wei, Zhongwang; Huntingford, Chris; Wang, Pei; Cui, Zhongyin; Ma, Ning; Wang, Lixin; Earth Sciences, School of Science
    Quantifying the transpiration fraction of evapotranspiration (T/ET) is crucial for understanding plant functionality in ecosystem water cycles, land‐atmosphere interactions, and the global water budget. However, the controls and mechanisms underlying the temporal change of T/ET remain poorly understood in arid and semiarid areas, especially for remote regions with sparse observations such as the Tibetan Plateau (TP). In this study, we used combined high‐frequency laser spectroscopy and chamber methods to constrain estimates of T/ET for an alpine meadow ecosystem in the central TP. The three isotopic end members in ET (δET), soil evaporation (δE), and plant transpiration (δT) were directly determined by three newly customized chambers. Results showed that the seasonal variations of δET, δE, and δT were strongly affected by the precipitation isotope (R2 = 0.53). The δ18O‐based T/ET agreed with that of δ2H. Isotope‐based T/ET ranged from 0.15 to 0.73 during the periods of observation, with an average of 0.43. This mean result was supported by T/ET derived from a two‐source model and eddy covariance observations. Our overarching finding is that at the seasonal timescale, surface soil water content (θ) dominated the change of T/ET, with leaf area index playing only a secondary role. Our study confirms the critical impact of soil water on the temporal change of T/ET in water‐limited regions such as the TP. This knowledge sheds light on diverse land‐surface processes, global hydrological cycles, and their modeling.
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    Seasonality of the Transpiration Fraction and Its Controls Across Typical Ecosystems Within the Heihe River Basin
    (Wiley, 2019) Tong, Yaqin; Wang, Pei; Li, Xiao-Yan; Wang, Lixin; Wu, Xiuchen; Shi, Fangzhong; Bai, Yan; Li, Engui; Wang, Jiaqi; Wang, Yang; Earth Sciences, School of Science
    Understanding the seasonality of the transpiration fraction (T/ET) of total terrestrial evapotranspiration (ET) is vital for coupling ecological and hydrological systems and quantifying the heterogeneity among various ecosystems. In this study, a two‐source model was used to estimate T/ET in five ecosystems over the Heihe River Basin. In situ measurements of daily energy flux, sap flow, and surface soil temperature were compared with model outputs for 2014 and 2015. Agreement between model predictions and observations demonstrates good performance in capturing the ecosystem seasonality of T/ET. In addition, sensitivity analysis indicated that the model is insensitive to errors in measured input variables and parameters. T/ET among the five sites showed only slight interannual fluctuations while exhibited significant seasonality. All the ecosystems presented a single‐peak trend, reaching the maximum value in July and fluctuating day to day. During the growing season, average T/ET was the highest for the cropland ecosystem (0.80 ± 0.13), followed by the alpine meadow ecosystem (0.79 ± 0.12), the desert riparian forest Populus euphratica (0.67 ± 0.07), the Tamarix ramosissima Ledeb desert riparian shrub ecosystem (0.67 ± 0.06), and the alpine swamp meadow (0.55 ± 0.23). Leaf area index exerted a first‐order control on T/ET and showed divergence among the five ecosystems because of different vegetation dynamics and environmental conditions (e.g., water availability or vapor pressure deficits). This study quantified transpiration fraction across diverse ecosystems within the same water basin and emphasized the biotic controls on the seasonality of the transpiration fraction.