28 results on '"Pin, Wang"'
Search Results
2. A prognostic nomogram for patients with HR+ mucinous breast carcinoma based on the SEER database and a Chinese cohort study
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Huiying Fang, Jian Yue, Hongzhong Li, Tiankuo Luan, Pin Wang, and Guosheng Ren
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SEER ,mucinous breast carcinoma ,nomogram ,propensity score matching analysis ,prognosis ,neoadjuvant chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PurposeThe study aimed to develop a nomogram model for individual prognosis prediction in patients with hormone receptors positive (HR+) mucinous breast carcinoma (MBC) and assess the value of neoadjuvant chemotherapy (NAC) in this context.MethodsA total of 6,850 HR+ MBC patients from the SEER database were identified and randomly (in a 7:3 ratio) divided into training cohorts and internal validation cohorts. 77 patients were enrolled from the Chongqing University Cancer Hospital as the external validation cohort. Independent risk factors affecting overall survival (OS) were selected using univariate and multivariate Cox regression analysis, and nomogram models were constructed and validated. A propensity score matching (PSM) approach was used in the exploration of the value of NAC versus adjuvant chemocherapy (AC) for long-term prognosis in HR+ MBC patients.ResultsMultivariate Cox regression analysis showed 8 independent prognostic factors: age, race, marital status, tumor size, distant metastasis, surgery, radiotherapy, and chemotherapy. The constructed nomogram model based on these 8 factors exhibited good consistency and accuracy. In the training group, internal validation group and external validation group, the high-risk groups demonstrated worse OS (p
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- 2024
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3. Bibliometric analysis of neuroinflammation and Alzheimer’s disease
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Wenxian Sun, Jin Gong, Shaoqi Li, Pin Wang, Xiaodong Han, Chang Xu, Heya Luan, Ruina Li, Boye Wen, and Cuibai Wei
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neuroinflammation ,Alzheimer’s disease ,bibliometrics ,VOSviewer ,CiteSpace ,microglia ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
BackgroundAlzheimer’s disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends.MethodsThis research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references.ResultsA total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood–brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024.ConclusionThis study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations.
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- 2024
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4. Evaluating EEG neurofeedback in sport psychology: a systematic review of RCT studies for insights into mechanisms and performance improvement
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Ming-Yang Cheng, Chien-Lin Yu, Xin An, Letong Wang, Chi-Lun Tsai, Fengxue Qi, and Kuo-Pin Wang
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EEG biofeedback ,mental training ,sport neuroscience ,sport performance enhancement ,brain waves ,brain training ,Psychology ,BF1-990 - Abstract
Electroencephalographic Neurofeedback Training (EEG NFT) aims to improve sport performance by teaching athletes to control their mental states, leading to better cognitive, emotional, and physical outcomes. The psychomotor efficiency hypothesis suggests that optimizing brain function could enhance athletic ability, indicating the potential of EEG NFT. However, evidence for EEG-NFT’s ability to alter critical brain activity patterns, such as sensorimotor rhythm and frontal midline theta—key for concentration and relaxation—is not fully established. Current research lacks standardized methods and comprehensive studies. This shortfall is due to inconsistent EEG target selection and insufficient focus on coherence in training. This review aims to provide empirical support for EEG target selection, conduct detailed control analyses, and examine the specificity of electrodes and frequencies to relation to the psychomotor efficiency hypothesis. Following the PRISMA method, 2,869 empirical studies were identified from PubMed, Science Direct, Web of Science, Embase, CNKI, and PsycINFO. Thirteen studies met the inclusion criteria: (i) proficient skill levels; (ii) use of EEG; (iii) neurofeedback training (NFT); (iv) motor performance metrics (reaction time, precision, dexterity, balance); (v) control group for NFT comparison; (vi) peer-reviewed English-language publication; and (vii) randomized controlled trial (RCT) design. Studies indicate that NFT can enhance sports performance, including improvements in shooting accuracy, golf putting, and overall motor skills, as supported by the psychomotor efficiency hypothesis. EEG NFT demonstrates potential in enhancing sports performance by optimizing performers’ mental states and psychomotor efficiency. However, the current body of research is hampered by inconsistent methodologies and a lack of standardized EEG target selection. To strengthen the empirical evidence supporting EEG NFT, future studies need to focus on standardizing target selection, employing rigorous control analyses, and investigating underexplored EEG markers. These steps are vital to bolster the evidence for EEG NFT and enhance its effectiveness in boosting sport performance.
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- 2024
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5. Effects of self-efficacy on frontal midline theta power and golf putting performance
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Chien-Lin Yu, Cheng-Wei Kao, Jia-Hao Wu, Eric Hung, Wei-Chun Chang, Ren-Ting Yang, Kuo-Pin Wang, and Tsung-Min Hung
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self-efficacy ,frontal midline theta ,attention ,sports performance ,golf-putting ,Psychology ,BF1-990 - Abstract
IntroductionSelf-efficacy (SE), defined as an individual's belief in their ability to complete a task, is linked to top-down attentional control, influencing motor performance in sports. Although the behavioral effects of SE are well-documented, there is a lack of research on the mechanisms through which SE affects sports performance. Our research aims to elucidate the neurophysiological mechanisms that underlie the impact of self-efficacy on sports performance. Specifically, we intend to explore the effects of low and high SE on frontal midline theta (Fmθ) activity, associated with sustained top-down attention, and on motor performance.MethodsWe recruited thirty-four professional golfers to perform 60 putts, during which their electroencephalographic activity was monitored. SE levels were assessed using a visual analog scale from 0 to 10 before each putt, with scores categorized into higher or lower SE based on each golfer's individual average score.ResultsPaired t-tests indicated that trials with higher SE scores had a higher putting success rate than those with lower SE scores (53.3% vs. 46.7%). Furthermore, trials associated with higher SE scores exhibited lower Fmθ activity compared to those with lower SE scores (4.49 vs. 5.18).DiscussionOur results suggest that higher SE is associated with reduced top-down attentional control, leading to improved putting performance. These findings support Bandura's theory of SE, which suggests that the effects of efficacy beliefs are mediated by cognitive, motivational, emotional, and decision-making processes. This study sheds light on the intermediate processes of SE by examining its impact on the anticipation of outcomes, sports performance, and attentional control prior to putting.
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- 2024
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6. A new EEG neurofeedback training approach in sports: the effects function-specific instruction of Mu rhythm and visuomotor skill performance
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Kuo-Pin Wang, Ming-Yang Cheng, Hatem Elbanna, and Thomas Schack
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complex visuomotor skills ,simple visuomotor skills ,Mu rhythm ,alpha rhythm ,mental training ,golf putting ,Psychology ,BF1-990 - Abstract
IntroductionAchieving optimal visuomotor performance in precision sports relies on maintaining an optimal psychological state during motor preparation. To uncover the optimal psychological state, extensive EEG studies have established a link between the Mu rhythm (8–13 Hz at Cz) and cognitive resource allocation during visuomotor tasks (i.e., golf or shooting). In addition, the new approach in EEG neurofeedback training (NFT), called the function-specific instruction (FSI) approach, for sports involves providing function-directed verbal instructions to assist individuals to control specific EEG parameters and align them with targeted brain activity features. While this approach was initially hypothesized to aid individuals in attaining a particular mental state during NFT, the impact of EEG-NFT involving Mu rhythm on visuomotor performance, especially when contrasting the traditional instruction (TI) approach with the FSI approach, underscores the necessity for additional exploration. Hence, the objective of this study is to investigate the impact of the FSI approach on modulating Mu rhythm through EEG-NFT in the context of visuomotor performance.MethodsThirty novice participants were recruited and divided into three groups: function-specific instruction (FSI, four females, six males; mean age = 27.00 ± 7.13), traditional instruction (TI, five females, five males; mean age = 27.00 ± 3.88), and sham control (SC, five females, five males; mean age = 27.80 ± 5.34). These groups engaged in a single-session EEG-NFT and performed golf putting tasks both before and after the EEG-NFT.ResultsThe results showed that within the FSI group, single-session NFT with augmented Mu power led to a significant decrease in putting performance (p = 0.013). Furthermore, we noted a marginal significance indicating a slight increase in Mu power and a reduction in the subjective sensation of action control following EEG-NFT (p = 0.119). While there was a positive correlation between Mu power and mean radial error in golf putting performance (p = 0.043), it is important to interpret this relationship cautiously in the context of reduced accuracy in golf putting.DiscussionThe findings emphasize the necessity for extended investigation to attain a more profound comprehension of the nuanced significance of Mu power in visuomotor performance. The study highlights the potential effectiveness of the FSI approach in EEG-NFT and in enhancing visuomotor performance, but it also emphasizes the potential impact of skill level and attentional control, particularly in complex visuomotor tasks.
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- 2023
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7. The severity of valvular heart disease in euthyroid individuals is associated with thyroid hormone levels but not with TSH levels
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Pin Wang, Sen Lu, Yan Yang, Limei Liu, Guangpeng Zhou, Jieling Zhu, Diejing Niu, Yi Wang, and Shaohua Wang
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thyroid hormone ,valvular heart disease ,euthyroid sick syndrome ,NYHA grades ,age ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundAbnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD).MethodThe thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed.ResultsNo difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p
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- 2023
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8. Single-cell RNA sequencing reveals tumor immune microenvironment in human hypopharygeal squamous cell carcinoma and lymphatic metastasis
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Ce Li, Rui Guan, Wenming Li, Dongmin Wei, Shengda Cao, Chenyang Xu, Fen Chang, Pin Wang, Long Chen, and Dapeng Lei
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single-cell RNA sequencing ,hypopharygeal squamous cell carcinoma ,tumor immune microenvironment ,IGHA1 ,IGHG1 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundHuman hypopharygeal squamous cell carcinoma (HSCC) is a common head and neck cancer with a poor prognosis in advanced stages. The occurrence and development of tumor is the result of mutual influence and co-evolution between tumor cells and tumor microenvironment (TME). Tumor immune microenvironment (TIME) refers to the immune microenvironment surrounding tumor cells. Studying TIME in HSCC could provide new targets and therapeutic strategies for HSCC.MethodsWe performed single-cell RNA sequencing (scRNA-seq) and analysis of hypopharyngeal carcinoma, paracancerous, and lymphoid tissues from five HSCC patients. Subdivide of B cells, T cells, macrophages cells, and monocytes and their distribution in three kinds of tissues as well as marker genes were analyzed. Different genes of IGHG1 plasma cells and SPP1+ macrophages between HSCC tissues, adjacent normal tissues and lymphatic tissues were analyzed. Additionally, we studied proliferating lymphocytes, T cells exhaustion, and T cell receptor (TCR) repertoire in three kinds of tissues.ResultsTranscriptome profiles of 132,869 single cells were obtained and grouped into seven cell clusters, including epithelial cells, lymphocytes, mononuclear phagocytics system (MPs), fibroblasts, endothelial cells (ECs), plasmacytoid dendritic cells (pDCs), and mast cells. Tumor metastasis occurred in three lymphoid tissues. Four distinct populations were identified from lymphocytes, including B cells, plasma cells, T cells and proliferating lymphocytes. We found IGHA1 and IGHG1 specific plasma cells significantly overexpressed in HSCC tissues compared with normal hypopharygeal tissues and lymphatic tissues. Five distinct populations from MPs were identified, including macrophages, monocytes, mature dendritic cells (DCs), Type 1 conventional dendritic cells (cDC1) and Type 2 conventional dendritic cells (cDC2). SPP1+ macrophages were significantly overexpressed in HSCC tissues and lymphatic tissues compared with normal hypopharygeal tissues, which are thought to be M2-type macrophages. Exhaustion of CD8+ Teff cells occurred in HSCC tissues. At last, we verified that IgA and IgG1 protein expression levels were significantly up-regulated in HSCC tissues compared to adjacent normal tissues.ConclusionOverall, this study revealed TIME in HSCC and lymphatic metastasis, and provided potential therapeutic targets for HSCC.
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- 2023
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9. Prognostic value of neutrophil extracellular trap signature in clear cell renal cell carcinoma
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Rong Li, Xuewen Jiang, Pin Wang, and Xiaoyan Liu
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clear cell renal cell carcinoma ,neutrophil extracellular traps ,prognosis signature ,validation ,multiomics data ,immune microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionClear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.MethodsClinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.ResultsA total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.ConclusionsThe NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.
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- 2023
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10. Corrigendum: A minimally manipulated preservation and virus inactivation method for amnion/chorion
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Shang Zhang, Lichang Gao, Pin Wang, Yuyan Ma, Xiaoliang Wang, Jie Wen, Yu Cheng, Changlin Liu, Chunxia Zhang, Changfeng Liu, Yongli Yan, and Chengru Zhao
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diabetic foot ulcer (DFU) ,chronic wound ,animal model ,amnion ,virus inactivation ,growth factor (GF) ,Biotechnology ,TP248.13-248.65 - Published
- 2023
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11. Immune microenvironment and clinical feature analyses based on a prognostic model in lymph node-positive breast cancer
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Nannan Lu, Changfang Fu, Lei Zhang, Yangyang You, Xiang Li, Qian Zhang, Pin Wang, and Xinghua Han
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breast cancer ,lymph node metastasis ,tumor-infiltrating lymphocyte ,LNPRS score ,prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundIf lymph node metastasis occurs in breast cancer patients, the disease can progress rapidly. Based on the infiltrative immune cells of breast cancer patients with lymph node positivity, we constructed the LNPRS for selecting prognostic predictors.MethodsThe LNPRS was established and the predictive value of the LNPRS was verified by independent testing cohorts. A nomogram was also established to confirm the therapeutic guidance significance of the LNPRS. The correlation of the LNPRS with tumor mutation burden, immune microenvironment score, immune checkpoints, the proportion of tumor-infiltrating immune cells, and GSEA and GSVA enrichment pathways were also evaluated.ResultsIn the training cohort, the overall survival of breast cancer patients who had high LNPRS was shorter than that of patients who had low LNPRS (7.98 years versus 20.42 years, P-value< 8.16E-11). The AUC values for 5-, 10-, and 15-years were 0.787, 0.739, and 0.800, respectively. The ability to predict prognosis for the LNPRS was also tested in 3 independent testing cohorts. Furthermore, the predictive value of the LNPRS for chemotherapy and immunotherapy was also proven. The GSEA and GSVA showed that the LNPRS was closely related to the activation of T and B lymphocytes and IFN-γ secretion. Moreover, breast cancer patients with low LNPRS had higher TME scores than those with high LNPRS.ConclusionWe can conclude that the LNPRS is a robust prognostic biomarker in breast cancer patients with positive lymph nodes and may be helpful for patients to make a clinical decision.
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- 2023
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12. Biocompatibility and osteoinductive ability of casein phosphopeptide modified polyetheretherketone
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Peng Qiu, Pin Wang, Min Liu, Tao Dai, Min Zheng, and Le Feng
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polyetheretherketone ,casein phosphopeptide ,surface modification ,cell adhesion ,cell proliferation ,osteoinductive ability ,Biotechnology ,TP248.13-248.65 - Abstract
Polyetheretherketone (PEEK) is a potential implant material for dental application due to its excellent mechanical properties. However, its biological inertness and poor osteoinductive ability limited its clinical application. Based on a lay-by-layer self-assembly technique, here we incorporated casein phosphopeptide (CPP) onto PEEK surface by a simple two-step strategy to address the poor osteoinductive ability of PEEK implants. In this study, the PEEK specimens were positively charged by 3-ammoniumpropyltriethoxysilane (APTES) modification, then the CPP was adsorbed onto the positively charged PEEK surface electrostatically to obtain CPP-modified PEEK (PEEK-CPP) specimens. The surface characterization, layer degradation, biocompatibility and osteoinductive ability of the PEEK-CPP specimens were studied in vitro. After CPP modification, the PEEK-CPP specimens had a porous and hydrophilic surface and presented enhanced cell adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. These findings indicated that CPP modification could significantly improve the biocompatibility and osteoinductive ability of PEEK-CPP implants in vitro. In a word, CPP modification is a promising strategy for the PEEK implants to achieve osseointegration.
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- 2023
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13. Nanoformulation improves antitumor efficacy of MAOI immune checkpoint blockade therapy without causing aggression-related side effects
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James Brown, Zhe Li, Xi Wang, Yu Jeong Kim, Yu-Chen Wang, Yanning Zuo, Weizhe Hong, Pin Wang, Bo Li, and Lili Yang
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monoamine oxidase inhibitors ,phenelzine ,immune checkpoint blockade ,nanoformulation ,cancer immunotherapy ,neurological side effects ,Therapeutics. Pharmacology ,RM1-950 - Abstract
MAOIs, a well-established class of antidepressant that operate through the inhibition of monoamine oxidase to increase available serotonin, have recently been identified as a surprisingly effective candidate for the circumvention of tumor-induced immune suppression due to their abilities to enhance antitumor T cell activity through autocrine serotonin signaling and depolarize alternatively activated tumor-associated macrophages through a reduction in reactive oxygen species production. However, this impressive class of antidepressants-turned-cancer-drugs can induce aggressive behavioral side effects when administered in immunotherapeutic doses. In this study, we investigated the possibility of avoiding these neurological side effects while simultaneously improving antitumor activity by establishing crosslinked multilamellar liposomal vesicles (cMLVs) containing the MAOI phenelzine (PLZ). Our results showed that cMLV-PLZ treatment increases antitumor efficacy in a B16-OVA mouse melanoma model compared to treatment with free phenelzine. We also found that nanoformulation resulted in the complete elimination of MAOI-related aggression. These findings suggest a promising direction for the future of MAOIs repurposed for cancer immunotherapies.
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- 2022
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14. Bioelectrical impedance spectroscopy can assist to identify the parathyroid gland during thyroid surgery
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Bin Wang, Zaoyang Liu, Jian Wu, Ying Liu, Pin Wang, Hong Liu, Haobin Wang, Tielin Wang, Juan Wang, Yan Tang, and Junyan Zhang
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bioelectrical impedance spectroscopy ,thyroid ,parathyroid gland ,lymph node ,adipose tissue ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ObjectiveThis study aimed to explore the effectiveness of bioelectrical impedance spectroscopy in the identification of parathyroid glands during thyroid surgeries.MethodAll patients who received thyroid surgeries at our department from January 2018 to February 2020 were recruited for this study. The bioelectrical impedance spectroscopy analyzer was applied to analyze on following tissues: thyroid tissues, lymph nodes, adipose tissues, and the tissues suspected to be parathyroid glands. Postoperative pathological reports were obtained as the golden standard to compare with the characteristic parameters obtained from bioelectrical impedance spectroscopy. The receiver operating characteristic curve analysis was used to assess the diagnostic value and the selection of the optimal threshold of these parameters from bioelectrical impedance spectroscopy.ResultsA total of 512 patients were enrolled in the study and 1898 specimens were measured by the bioelectrical impedance spectroscopy analyzer. There were significant differences in the parameter of fc among parathyroid glands, thyroid tissues, lymph nodes, and adipose tissues (252.2 ± 45.8 vs 144.7 ± 26.1, 491.7 ± 87.4, 602.3 ± 57.3; P
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- 2022
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15. A minimally manipulated preservation and virus inactivation method for amnion/chorion
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Shang Zhang, Lichang Gao, Pin Wang, Yuyan Ma, Xiaoliang Wang, Jie Wen, Yu Cheng, Changlin Liu, Chunxia Zhang, Changfeng Liu, Yongli Yan, and Chengru Zhao
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diabetic foot ulcer (DFU) ,chronic wound ,animal model ,amnion ,virus inactivation ,growth factor (GF) ,Biotechnology ,TP248.13-248.65 - Abstract
Allogeneic amnion tissues have been widely used in tissue repair and regeneration, especially a remarkable trend of clinical uses in chronic wound repair. The virus inactivation procedures are necessary and required to be verified for the clinical use and approval of biological products. Cobalt-60 (Co-60) or electron-beam (e-beam) is the common procedure for virus and bacterial reduction, but the excessive dose of irradiation was reported to be harmful to biological products. Herein, we present a riboflavin (RB)-ultraviolet light (UV) method for virus inactivation of amnion and chorion tissues. We used the standard in vitro limiting dilution assay to test the viral reduction capacity of the RB-UV method on amnion or chorion tissues loaded with four types of model viruses. We found RB-UV was a very effective procedure for inactivating viruses of amnion and chorion tissues, which could be used as a complementary method to Co-60 irradiation. In addition, we also screened the washing solutions and drying methods for the retention of growth factors.
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- 2022
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16. Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas
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Shichuan Tan, Ryan Spear, Juan Zhao, Xiulian Sun, and Pin Wang
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E3-related genes ,prognosis ,tumor immune microenvironment ,risk signature ,low-grade gliomas ,Genetics ,QH426-470 - Abstract
Gliomas, a type of primary brain tumor, have emerged as a threat to global mortality due to their high heterogeneity and mortality. A low-grade glioma (LGG), although less aggressive compared with glioblastoma, still exhibits high recurrence and malignant progression. Ubiquitination is one of the most important posttranslational modifications that contribute to carcinogenesis and cancer recurrence. E3-related genes (E3RGs) play essential roles in the process of ubiquitination. Yet, the biological function and clinical significance of E3RGs in LGGs need further exploration. In this study, differentially expressed genes (DEGs) were screened by three differential expression analyses of LGG samples from The Cancer Genome Atlas (TCGA) database. DEGs with prognostic significance were selected by the univariate Cox regression analysis and log-rank statistical test. The LASSO-COX method was performed to identify an E3-related prognostic signature consisting of seven genes AURKA, PCGF2, MAP3K1, TRIM34, PRKN, TLE3, and TRIM17. The Chinese Glioma Genome Atlas (CGGA) dataset was used as the validation cohort. Kaplan–Meier survival analysis showed that LGG patients in the low-risk group had significantly higher overall survival time than those in the high-risk group in both TCGA and CGGA cohorts. Furthermore, multivariate Cox regression analysis revealed that the E3RG signature could be used as an independent prognostic factor. A nomogram based on the E3RG signature was then established and provided the prediction of the 1-, 3-, and 5-year survival probability of patients with LGGs. Moreover, DEGs were analyzed based on the risk signature, on which function analyses were performed. GO and KEGG analyses uncovered gene enrichment in extracellular matrix–related functions and immune-related biological processes in the high-risk group. GSEA revealed high enrichment in pathways that promote tumorigenesis and progression in the high-risk group. Furthermore, ESTIMATE algorithm analysis showed a significant difference in immune and stroma activity between high- and low-risk groups. Positive correlations between the risk signature and the tumor microenvironment immune cell infiltration and immune checkpoint molecules were also observed, implying that patients with the high-risk score may have better responses to immunotherapy. Overall, our findings might provide potential diagnostic and prognostic markers for LGG patients and offer meaningful insight for individualized treatment.
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- 2022
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17. A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer
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Binbin Yuan, Chengfei Jiang, Lingyan Chen, Lihui Wen, Jinlong Cui, Min Chen, Shu Zhang, Lin Zhou, Yimeng Cai, Jian-Hua Mao, Xiaoping Zou, Bo Hang, and Pin Wang
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gastric cancer ,immunotherapy ,immune checkpoint blockade ,immune checkpoint inhibitors ,DNA repair gene signature ,prognostic biomarker ,Biology (General) ,QH301-705.5 - Abstract
Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).
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- 2022
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18. Endogenous Protective Factors and Potential Therapeutic Agents for Diabetes-Associated Atherosclerosis
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Chaoqun Wang, Jin Chen, Pin Wang, Shengli Qing, Wenwen Li, and Jin Lu
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endogenous protective factors ,analogues ,diabetes mellitus ,atherosclerosis ,therapy ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
The complications of macrovascular atherosclerosis are the leading cause of disability and mortality in patients with diabetes. It is generally believed that the pathogenesis of diabetic vascular complications is initiated by the imbalance between injury and endogenous protective factors. Multiple endogenous protective factors secreted by endothelium, liver, skeletal muscle and other tissues are recognized of their importance in combating injury factors and maintaining the homeostasis of vasculatures in diabetes. Among them, glucagon-like peptide-1 based drugs were clinically proven to be effective and recommended as the first-line medicine for the treatment of type 2 diabetic patients with high risks or established arteriosclerotic cardiovascular disease (CVD). Some molecules such as irisin and lipoxins have recently been perceived as new protective factors on diabetic atherosclerosis, while the protective role of HDL has been reinterpreted since the failure of several clinical trials to raise HDL therapy on cardiovascular events. The current review aims to summarize systemic endogenous protective factors for diabetes-associated atherosclerosis and discuss their mechanisms and potential therapeutic strategy or their analogues. In particular, we focus on the existing barriers or obstacles that need to be overcome in developing new therapeutic approaches for macrovascular complications of diabetes.
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- 2022
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19. IFN-γ-Primed hUCMSCs Significantly Reduced Inflammation via the Foxp3/ROR-γt/STAT3 Signaling Pathway in an Animal Model of Multiple Sclerosis
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Xiao Ling, Teng Wang, Chao Han, Pin Wang, Xiaoli Liu, Chengyun Zheng, Jianzhong Bi, and Xiaoyan Zhou
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IFN-γ-primed human umbilical cord mesenchymal stem cell (IFN-γ-hUCMSCs) ,multiple sclerosis (MS) ,experimental autoimmune encephalomyelitis (EAE) ,indoleamine 2,3-dioxygenease (IDO) ,Foxp3/ROR-γt/STAT3 signaling pathway ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Our previous study showed that interferon gamma (IFN-γ) might enhance the immunosuppressive properties of mesenchymal stem cells (MSCs) by upregulating the expression of indoleamine 2,3-dioxygenease. Therefore, we treated experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis (MS), with IFN-γ-primed human umbilical cord MSCs (IFN-γ-hUCMSCs). This study aimed to investigate the potential therapeutic effects of IFN-γ-hUCMSCs transplantation and to identify the biological pathways involved in EAE mice. Firstly, the body weights and clinical scores of EAE mice were recorded before and after treatment. Then, the inflammatory cytokine levels in splenic cell supernatants were quantified by enzyme-linked immunosorbent assay. Finally, the mRNA expression levels of signal transducer and activator of transduction 3 (STAT3), retinoic acid-related orphan receptor gamma t (ROR-γt), and forkhead box P3 (Foxp3) were detected by quantitative reverse transcription polymerase chain reaction. We observed that IFN-γ-hUCMSCs transplantation significantly alleviated body weight loss and decreased the clinical scores of mice. Additionally, IFN-γ-hUCMSCs transplantation could regulate the production of inflammatory cytokines, interleukin (IL)-10 and IL-17, thereby showing more potent treatment efficacy than human umbilical cord MSCs (hUCMSCs) transplantation (p < 0.05). Compared with the EAE group, the expressions of STAT3 and ROR-γt in the transplantation groups were significantly decreased, but the expression of Foxp3 was significantly upregulated in the IFN-γ-hUCMSCs transplantation group compared to that in the hUCMSCs transplantation group. We assumed that IFN-γ-hUCMSCs may affect the balance of T helper 17 (Th17) cells/regulatory T cells (Tregs) through the Foxp3/ROR-γt/STAT3 signaling pathway to reduce the inflammatory response, thereby improving the clinical symptoms of EAE mice. Our study demonstrated that transplantation of IFN-γ-hUCMSCs could reduce inflammation in EAE mice via the Foxp3/ROR-γt/STAT3 signaling pathway, highlighting the therapeutic effects of IFN-γ-hUCMSCs in patients with MS.
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- 2022
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20. Pattern Recognition Receptors (PRRs) in Macrophages Possess Prognosis and Immunotherapy Potential for Melanoma
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Qihang Zhao, Qiang Wang, Tengjiao Wang, Junfang Xu, Tingting Li, Qiuyan Liu, Qinghua Yao, and Pin Wang
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pattern recognition receptors ,skin cutaneous melanoma ,prognosis ,immune-infiltration ,macrophage ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundPattern recognition receptors (PRRs) family plays a vital role in the initial stage of innate immune response and the subsequent activation of adaptive immunity. Increasing evidences have indicated that several PRRs play critical roles in the progress of inflammation and tumorigenesis. However, the comprehensive significance of PRRs family in clinical prognosis of different cancers is still elusive.MethodsWe analyzed expression of 20 canonical PRRs in tumor samples from 9502 patients of 33 tumor types. Next, we used expression profiles of PRRs in skin cutaneous melanoma (SKCM) to build a Cox prognosis model. Then, we analyzed immune infiltration features and immune activity of high risk score and low risk score patients. Finally, we analyzed the single-cell sequencing data of different cancers and detected the expression of PRRs in mouse melanoma model to identify PRRs-expressing cell types.ResultsWe found PRRs had a significantly positive correlation with prognosis in SKCM rather than other tumors, and PRR-based Cox model had a much better prognosis potential than any single PRR. Further analysis shows risk score could indicate immunocyte infiltration and immune activity in SKCM. We also found the expressions of some PRR genes were highly correlated with the expression of immune checkpoints molecules in SKCM, indicating they could be indicators for clinical immune therapy. Finally, we found only in SKCM samples, the expression of PRRs is especially high in a subpopulation of macrophages with a trait of CD206 low expression, probably explaining why PRRs have prognosis potential in melanoma.ConclusionsOur study reveals PRR family in macrophages has a positive prognosis potential in melanoma and could be valuable for clinical prognosis and immune therapy.
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- 2021
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21. Plasma-Derived Exosomal ALIX as a Novel Biomarker for Diagnosis and Classification of Pancreatic Cancer
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Jie Yang, Yixuan Zhang, Xin Gao, Yue Yuan, Jing Zhao, Siqi Zhou, Hui Wang, Lei Wang, Guifang Xu, Xihan Li, Pin Wang, Xiaoping Zou, Dongming Zhu, Ying Lv, and Shu Zhang
- Subjects
exosomes ,pancreatic cancer ,proteomic profile ,ALIX ,diagnostic biomarker ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundPancreatic cancer (PC) has a dismal prognosis due to its insidious early symptoms and poor early detection rate. Exosomes can be released by various cell types and tend to be a potential novel biomarker for PC detection. In this study, we explored the proteomic profiles of plasma exosomes collected from patients with PC at different stages and other pancreatic diseases.MethodsPlasma samples were collected from six groups of patients, including PC at stage I/II, PC at stage III/IV, well-differentiated pancreatic neuroendocrine tumor (P-NET), pancreatic cystic lesions (PCLs), chronic pancreatitis (CP), and healthy controls (HCs). Plasma-derived exosomes were isolated by ultracentrifugation and identified routinely. Isobaric tags for relative and absolute quantification (iTRAQ) based proteomic analysis along with bioinformatic analysis were performed to elucidate the biological functions of proteins. The expression of exosomal ALIX was further confirmed by enzyme-linked immunosorbent assay in a larger cohort of patients. Furthermore, receiver operating characteristic curve analysis was applied to evaluate the potential of ALIX as a novel diagnostic biomarker.ResultsThe proteomic profile revealed a total of 623 proteins expressed among the six groups, and 16 proteins with differential degrees of abundance were found in PC vs. other pancreatic diseases (including P-NET, PCLs, and CP). Based on the results of proteomic and bioinformatic analyses, exosomal ALIX was subsequently selected as a novel biomarker for PC detection and validated in another clinical cohort. We noticed that ALIX expression was elevated in PC patients compared with patients with other pancreatic diseases or HC, and it was also closely associated with TNM stage and distant metastasis. Interestingly, the combination of exosomal ALIX and serum CA199 has greater values in differentiating both early vs. late PC (AUC value 0.872) and PC vs. other pancreatic diseases (AUC value 0.910) than either ALIX or CA199 alone.ConclusionIn summary, our study demonstrated that based on proteomic profiling, proteins isolated from the plasma-derived exosomes may function as ideal non-invasive biomarkers for the clinical diagnosis of PC. Importantly, exosomal ALIX combined with CA199 has great potentials in detection of PC, especially in distinguishing PC patients at early stages from advanced stages.
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- 2021
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22. Superior Performance in Skilled Golfers Characterized by Dynamic Neuromotor Processes Related to Attentional Focus
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Kuo-Pin Wang, Cornelia Frank, Yen-yu Tsai, Kao-Hung Lin, Tai-Ting Chen, Ming-Yang Cheng, Chung-Ju Huang, Tsung-Min Hung, and Thomas Schack
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electroencephalography ,precision sports ,attention ,constrained action hypothesis ,meshed control theory ,Psychology ,BF1-990 - Abstract
The meshed control theory assumes that cognitive control and automatic processes work together in the natural attention of experts for superior performance. However, the methods adopted by previous studies limit their capacity to provide in-depth information on the neuromotor processes. This experiment tested the theory with an alternative approach. Twelve skilled golfers were recruited to perform a putting task under three conditions: (1) normal condition, with no focus instruction (NC), (2) external focus of attention condition (EC), and (3) internal focus of attention condition (IC). Four blocks of 10 putts each were performed under each condition. The putting success rate and accuracy were measured and electroencephalographies (EEGs) were recorded. The behavioral results showed that the NC produced a higher putting success rate and accuracy than the EC and IC. The EEG data showed that the skilled golfers’ attentional processes in the NC initially resembled those in the EC and then moved toward those in the IC just before putting. This indicates a switch from more automatic processes to cognitive control processes while preparing to putt. The findings offer support for the meshed control theory and indicate the dynamic nature of neuromotor processes for the superior performance of athletes in challenging situations.
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- 2021
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23. SARA-GAN: Self-Attention and Relative Average Discriminator Based Generative Adversarial Networks for Fast Compressed Sensing MRI Reconstruction
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Zhenmou Yuan, Mingfeng Jiang, Yaming Wang, Bo Wei, Yongming Li, Pin Wang, Wade Menpes-Smith, Zhangming Niu, and Guang Yang
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MRI ,reconstruction ,deep learning ,compressive sensing ,neuroinformatics ,artificial intelligence ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Research on undersampled magnetic resonance image (MRI) reconstruction can increase the speed of MRI imaging and reduce patient suffering. In this paper, an undersampled MRI reconstruction method based on Generative Adversarial Networks with the Self-Attention mechanism and the Relative Average discriminator (SARA-GAN) is proposed. In our SARA-GAN, the relative average discriminator theory is applied to make full use of the prior knowledge, in which half of the input data of the discriminator is true and half is fake. At the same time, a self-attention mechanism is incorporated into the high-layer of the generator to build long-range dependence of the image, which can overcome the problem of limited convolution kernel size. Besides, spectral normalization is employed to stabilize the training process. Compared with three widely used GAN-based MRI reconstruction methods, i.e., DAGAN, DAWGAN, and DAWGAN-GP, the proposed method can obtain a higher peak signal-to-noise ratio (PSNR) and structural similarity index measure(SSIM), and the details of the reconstructed image are more abundant and more realistic for further clinical scrutinization and diagnostic tasks.
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- 2020
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24. The Opening of Pandora's Box: An Emerging Role of Long Noncoding RNA in Viral Infections
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Pin Wang
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lncRNA ,long noncoding RNA ,immune response ,viral infection ,antiviral immunity ,RNA-protein interaction ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Emerging evidence has proved that long noncoding RNAs (lncRNAs) participate in various physiological and pathological processes. Recent evidence has demonstrated that lncRNAs are crucial regulators of virus infections and antiviral immune responses. Upon viral infections, significant changes take place at the transcriptional level and the majority of the expression modifications occur in lncRNAs from both the host and viral genomes with dynamic regulatory courses. These lncRNAs exert diverse effects. Some are antiviral either through directly inhibiting viral infections or through stimulating antiviral immune responses, while others are pro-viral through directly promoting virus replication or through influencing cellular status, such as suppressing antiviral mechanisms. Consequently, these dynamic regulations lead to disparate pathophysiological outcomes and clinical manifestations. This review will focus on the roles of lncRNAs in viral infection and antiviral responses, summarize expression patterns of both host- and virally derived lncRNAs, describe their acting stages and modes of action, discuss challenges and novel concepts, and propose solutions and perspectives. Research into lncRNA will help identify novel viral infection-related regulators and design preventative and therapeutic strategies against virus-related diseases and immune disorders.
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- 2019
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25. Effects of Badminton Expertise on Representational Momentum: A Combination of Cross-Sectional and Longitudinal Studies
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Hua Jin, Pin Wang, Zhuo Fang, Xin Di, Zhuo’er Ye, Guiping Xu, Huiyan Lin, Yongmin Cheng, Yongjie Li, Yong Xu, and Hengyi Rao
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representational momentum ,badminton training ,causal relationships ,transfer ,cross-sectional ,longitudinal ,Psychology ,BF1-990 - Abstract
Representational momentum (RM) has been found to be magnified in experts (e.g., sport players) with respect to both real and implied motion in expert-familiar domains. However, it remains unclear whether similar effects can be achieved in expert-unfamiliar domains, especially within the context of implied motion. To answer this question, we conducted two independent experiments using an implied motion paradigm and examined the expert effects of badminton training on RM in both adult and child players. In Experiment 1, we used a cross-sectional design and compared RM between adult professional badminton players and matched controls. The results revealed significantly enhanced RM for adult players, supporting the expert effect in expert-unfamiliar domains for implied motion. However, cross-sectional studies could not ascertain whether the observed expert effect was due to innate factors or expertise acquirement. Therefore, in Experiment 2, we used a longitudinal design and compared RM between two groups of child participants, naming child players who had enrolled professional badminton training program at a sports school and age-matched peer non-players who attended an ordinary primary school without sports training. Before training, there were no differences in RM among child players, their non-player peers, and adult non-players. However, after 4 years of badminton training, child players demonstrated significantly enhanced RM compared to themselves prior to training. The increased RM observed in both adult and child players suggests that badminton expertise modulates implied motion RM.
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- 2017
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26. The role of medial frontal gyrus in action anticipation in professional badminton players
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Huan Xu, Pin Wang, Zhuo’er Ye, Xin Di, Guiping Xu, Lei Mo, Huiyan Lin, Hengyi Rao, and Hua Jin
- Subjects
fMRI ,functional connectivity ,medial frontal cortex. ,action anticipation ,professional badminton players ,Psychology ,BF1-990 - Abstract
Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent (BOLD) activation was assessed by means of functional magnetic resonance imaging (fMRI). Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus, right inferior parietal lobule, left insula and particularly, and left medial frontal cortex.
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- 2016
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27. Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG + AML.
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Yao, Sun, Jianlin, Chen, Yarong, Liu, Botao, Li, Qinghan, Wang, Hongliang, Fang, Lu, Zhang, Hongmei, Ning, Pin, Wang, Hu, Chen, Liangding, Hu, and Bin, Zhang
- Subjects
HEMATOPOIETIC stem cell transplantation ,T cells ,ACUTE myeloid leukemia ,TRANSPLANTATION of organs, tissues, etc. - Abstract
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG + AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG -positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG + AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG + AML without affecting the full donor chimerism and myeloid implantation. [ABSTRACT FROM AUTHOR]
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- 2019
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28. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players.
- Author
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Huan Xu, Pin Wang, Zhuo’er Ye, Xin Di, Guiping Xu, Lei Mo, Huiyan Lin, Hengyi Rao, and Hua Jin
- Abstract
Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent activation was assessed by means of functional magnetic resonance imaging. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus, right inferior parietal lobule, left insula and particularly, and left medial frontal cortex. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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