Browsing by Author "Li, Jing"
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Item A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2(Springer Nature, 2023) Yin, Qian; Luo, Wei; Mallajosyula, Vamsee; Bo, Yang; Guo, Jing; Xie, Jinghang; Sun, Meng; Verma, Rohit; Li, Chunfeng; Constantz, Christian M.; Wagar, Lisa E.; Li, Jing; Sola, Elsa; Gupta, Neha; Wang, Chunlin; Kask, Oliver; Chen, Xin; Yuan, Xue; Wu, Nicholas C.; Rao, Jianghong; Chien, Yueh-hsiu; Cheng, Jianjun; Pulendran, Bali; Davis, Mark M.; Microbiology and Immunology, School of MedicineThe ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.Item Aircraft noise, like heat stress, causes cognitive impairments via similar mechanisms in male mice(Elsevier, 2021) Sun, Gang; Lin, Xiaojing; Yi, Xueqing; Zhang, Peng; Liu, Ruoxu; Fu, Bo; Sun, Yating; Li, Jing; Jiao, Shuxin; Tian, Tian; Xu, Xiao-Ming; Tseng, Kuang-Wen; Lin, Cheng-Hsien; Neurological Surgery, School of MedicineTo our knowledge, little evidence is available about effects of aircraft noise (AN), a non-chemical stressor, on cognitive function. Again, it is unknown whether or not the heat stress (HS)-induced cognitive deficits can be exacerbated by AN. The adult male mice were assigned to four groups: group 1 mice exposed to non-HS (24-26 °C 2 h daily for 4 consecutive days) and white noise (WN) (2 h daily for 4 consecutive days), group 2 mice exposed to WN and HS (32-34 °C 2 h daily for 4 consecutive days), group 3 mice exposed to AN and non-HS (2 h daily for 4 consecutive days) and group 4 mice exposed to AN and HS (2 h daily for consecutive 4 days). Cognitive function were determined by passive avoidance, Y-maze, Morris water maze, and novel object recognition tests. Gut barrier and blood-brain-barrier (BBB) permeability, upload of lipopolysaccharide (LPS) translocation, systemic and central inflammation, and stress reactions were examined. Heat stressed mice displayed both increased stress reactions and learning and memory loss. Heat stress also caused gut barrier hyperpermeability, increased upload of LPS translocation, systemic inflammation, BBB disruption and hippocampal neuroinflammation. Aircraft noise stressed mice did not display systemic inflammation but caused gut barrier hyperpermeability, increased upload of LPS translocation, increased stress reactions, BBB disruption, hippocampal neuroinflammation and cognitive deficits. Aircraft noise exposure further exacerbated the heat stress-induced cognitive deficits and its complications. Our data suggest that AN, like HS, causes cognitive impairments via similar mechanisms in male mice.Item Associations of Nutritional, Environmental, and Metabolic Biomarkers with Diabetes-Related Mortality in U.S. Adults: The Third National Health and Nutrition Examination Surveys between 1988–1994 and 2016(MDPI, 2022-06-24) Zhang, Xi; Ardeshirrouhanifard, Shirin; Li, Jing; Li, Mingyue; Dai, Hongji; Song, Yiqing; Epidemiology, School of Public HealthBackground: Nutritional, environmental, and metabolic status may play a role in affecting the progression and prognosis of type 2 diabetes. However, results in identifying prognostic biomarkers among diabetic patients have been inconsistent and inconclusive. We aimed to evaluate the associations of nutritional, environmental, and metabolic status with disease progression and prognosis among diabetic patients. Methods: In a nationally representative sample in the NHANES III (The Third National Health and Nutrition Examination Survey, 1988−1994), we analyzed available data on 44 biomarkers among 2113 diabetic patients aged 20 to 90 years (mean age: 58.2 years) with mortality data followed up through 2016. A panel of 44 biomarkers from blood and urine specimens available from NHANES III were included in this study and the main outcomes as well as the measures are mortalities from all-causes. We performed weighted logistic regression analyses after controlling potential confounders. To assess incremental prognostic values of promising biomarkers beyond traditional risk factors, we compared c-statistics of the adjusted models with and without biomarkers, separately. Results: In total, 1387 (65.2%) deaths were documented between 1988 and 2016. We observed an increased risk of all-cause mortality associated with higher levels of serum C-reactive protein (p for trend = 0.0004), thyroid stimulating hormone (p for trend = 0.04), lactate dehydrogenase (p for trend = 0.02), gamma glutamyl transferase (p for trend = 0.02), and plasma fibrinogen (p for trend = 0.03), and urine albumin (p for trend < 0.0001). In contrast, higher levels of serum sodium (p for trend = 0.005), alpha carotene (p for trend = 0.006), and albumin (p for trend = 0.005) were associated with a decreased risk of all-cause mortality. In addition, these significant associations were not modified by age, sex, or race. Inclusion of thyroid stimulating hormone (p = 0.03), fibrinogen (p = 0.01), and urine albumin (p < 0.0001), separately, modestly improved the discriminatory ability for predicting all-cause mortality among diabetic patients. Conclusions: Our nationwide study findings provide strong evidence that some nutritional, environmental, and metabolic biomarkers were significant predictors of all-cause mortality among diabetic patients and may have potential clinical value for improving stratification of mortality risk.Item Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China(Oxford University Press, 2020-05-15) Deng, Xiaowei; Yang, Juan; Wang, Wei; Wang, Xiling; Zhou, Jiaxin; Chen, Zhiyuan; Li, Jing; Chen, Yinzi; Yan, Han; Zhang, Juanjuan; Zhang, Yongli; Wang, Yan; Qiu, Qi; Gong, Hui; Wei, Xianglin; Wang, Lili; Sun, Kaiyuan; Wu, Peng; Ajelli, Marco; Cowling, Benjamin J.; Viboud, Cecile; Yu, Hongjie; Epidemiology, School of Public HealthObjective To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. Methods We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. Results We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year; 95%CI: 1.11-1.16), and being male (OR 1.83; 95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. Conclusions Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.Item Clinicopathological and Prognostic Characteristics in Dedifferentiated/Poorly Differentiated Chordomas: A Pooled Analysis of Individual Patient Data From 58 Studies and Comparison With Conventional Chordomas(Frontiers Media, 2021-08-13) Liu, Fu-Sheng; Zheng, Bo-Wen; Zhang, Tao-Lan; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Huang, Wei; Zou, Ming-Xiang; Radiation Oncology, School of MedicineBackground: Currently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC). Methods: Literature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis. Results: Fifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables. Conclusions: These data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.Item Clinicopathological and Prognostic Characteristics in Spinal Chondroblastomas: A Pooled Analysis of Individual Patient Data From a Single Institute and 27 Studies(Sage, 2023) Zheng, Bo-Wen; Huang, Wei; Liu, Fu-Sheng; Zhang, Tao-Lan; Wang, Xiao-Bin; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of MedicineStudy design: Retrospective pooled analysis of individual patient data. Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.Item Coagulopathy as a Prodrome of Cytokine Storm in COVID-19-Infected Patients(Frontiers in Medicine, 2020-10) Guo, Hui; Sheng, Ying; Li, Wei; Li, Fei; Xie, Zongyu; Li, Jing; Zhu, Yuhe; Geng, Jian; Liu, Gang; Wang, LeJian; Li, Jing; Wang, Fengchao; School of NursingBackground The rapid coronavirus disease 2019 (COVID-19) pandemic has hit hard on the world and causes panic since the virus causes serious respiratory infectious illness and easily leads to severe conditions such as immune system overactivation or cytokine storm. Due to the limited knowledge of this infectious course of this coronavirus and a lack of an effective treatment for this fatal disease, the mortality remains high. The emergence of cytokine storm in patients on severe condition has been reported as the top reason of the death of patients with COVID-19 infection. However, the causative mechanism of cytokine storm remains elusive. Thus, we aim to observe the association of coagulopathy (D-dimer) with cytokine (i.e. IL-6) and CT imaging in COVID-19 infected patients. Methods In this retrospective observational study, we systematically analyzed the comprehensive clinical laboratory data of COVID-19 positive patients in different illness groups of mild, moderate, severe conditions according to Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition). T tests and Chi-square tests were used for two-group comparisons. One-way ANOVA was used for three-group comparisons. Pearson and spearman correlation coefficients of the D-dimer level with IL-6 and CT imaging were computed at baseline. With regular liquid biopsy approach, D-dimer, IL-6, NLR was recorded repeatedly with time curve to investigate the disease progression, along with CT imaging, and other indicators. Results All the 64 patients were clinically evaluated and classified into three groups of mild (32 cases), moderate (23 cases), severe (9 cases). D-dimer level positively correlated with IL-6 (R=0.5) at the base line when COVID-19 infected patients were admitted. In addition, we observed that D-dimer rises early than cytokine storm represented by IL-6 surge, which suggests that coagulopathy might act as trigger to potentiate cytokines storm. Conclusion Integrated analysis revealed the positive correlation of coagulopathy with cytokine storm in COVID-19 infected patients, D-dimer rise early, which indicated coagulopathy act as a prodrome of cytokine storm. Coagulopathy can be used to monitor early cytokine storm in COVID-19 infected patients.Item Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1(Wiley, 2024) Zhang, Tao-Lan; Zheng, Bo-Wen; Xia, Chao; Wu, Peng-Fei; Zheng, Bo-Yv; Jiang, Ling-Xiang; Li, Jing; Lv, Guo-Hua; Zhou, Hong; Huang, Wei; Zou, Ming-Xiang; Radiation Oncology, School of MedicineCurrently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.Item Identification of Key Parameters Affecting Energy Consumption of an Air Handling Unit(ASME, 2016-11) Goodman, David; Chen, Jie; Razban, Ali; Li, Jing; Engineering Technology, School of Engineering and TechnologyAir handling unit system (AHU) is one of the series of mechanical systems that regulate and circulate the air through the ducts inside the buildings. In a commercial setting, air handling units accounted for more than 50% of the total energy cost of the building in 2013. The energy efficiency of the system depends on multiple factors. The set points of discharge air temperature and supply air static pressure are important ones. ASHRAE Standard 90.1-2010 requires multi-zone HVAC systems to implement supply air temperature reset. Energy is wasted if the set points are set constant. However, the waste has never been quantified. The objectives of this study were to (1) develop and validate a mathematical model, which can be used to predict the system performance in response to various controls, specifically the set-point control strategies, and associated energy consumption, and (2) to recommend measures for optimizing the AHU performance by optimizing the setting schedules. In this research, a gray box model was established to evaluate the performance of an AHU. Individual components were modeled using energy and mass balance governing equations that represent the inherent physical processes and interactions with other components. Engineering Equation Solver (EES) was selected for system simulation due to its capabilities of finding the solutions of a large set of complicated equations. The model was validated using two sets of sub hourly real time data. The model performance was evaluated employing Mean Absolute Percentage Error (MAPE) and Root Mean Square Deviation (RMSD). The model was used to create the baseline of energy consumption with constant set points and predict the energy savings using two different reset schedules. The AHU, which serves the entire basement of a campus building on IUPUI campus, was used for this study. It normally has constant set points of discharge air temperature and supply air static pressure. The AHU was monitored using sensors. The data were filtered and transferred to a Building Automation system. Operation information and design specifications of the AHU were collected. Two reset schedules were investigated to determine the better control strategy to minimize energy consumption of the AHU. Discharge air temperature was reset based on return air temperature (RA-T) with a linear reset schedule from March 4 to March 7. Static pressure of the supply air was reset based on the widest open Variable Air Volume (VAV) box damper position from March 20 to March 23. Additionally, uncertainty propagation method was used to identify the dominant parameters affecting the energy consumption. Results indicated that 17% energy savings was achieved using discharge air temperature reset while the energy consumption reduced by 7% using static pressure reset. The results also indicated that outside air temperature, supply airflow rate and return air temperature were the key parameters that impact the overall energy consumption.Item Integrating single-cell and spatial transcriptomics reveals endoplasmic reticulum stress-related CAF subpopulations associated with chordoma progression(Oxford University Press, 2024) Zhang, Tao-Lan; Xia, Chao; Zheng, Bo-Wen; Hu, Hai-Hong; Jiang, Ling-Xiang; Escobar, David; Zheng, Bo-Yv; Chen, Tian-Dong; Li, Jing; Lv, Guo-Hua; Huang, Wei; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of MedicineBackground: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. Results: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. Conclusions: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.