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Yuening An,1 Aitao Lu,1 Wanyi Chen,1 Shengping Xue,1 Xiayao Ke,1 Jiayi Li,1 Weiyan He2 1Philosophy and Social Science Laboratory of Reading and Development in Children and Adolescents (South China Normal University), Ministry of Education, China; School of Psychology, South China Normal University, Guangzhou People’s Republic of China; 2Yanshan County Ethnic High School, Yanshan County, Wenshan Prefecture, Wenshan, Yunnan Province, People’s Republic of ChinaCorrespondence: Aitao Lu, Center for Studies of Psychological Application, South China Normal University, Guangzhou, People’s Republic of China, Tel +86 8521-6510, Fax +86 8521-6033, Email lu_yoyo@yeah.net; atlupsy@gmail.comIntroduction: While numerous studies have investigated the correlations between Belief in a Just World (BJW) and various variables, research on its stability and changes among different individuals, particularly in China, remains limited.Methods: This study aims to identify the classification and trajectories of BJW among Chinese adolescents using a person-oriented approach, including latent profile analysis and latent transition analysis. It also examines the impact of social status on BJW and its influence on self-regulated learning. The longitudinal data were collected from 756 Chinese high school students (35.71% male, Mage = 16.00, age range = 14– 19).Results: Three distinct BJW profiles were identified: High-level BJW (~33%), Moderate-level BJW (~51%), and Low-level BJW (~14%). The findings indicate that membership in moderate and high BJW profiles was relatively stable, while the low-level BJW profile showed moderate stability. Higher perceptions of BJW were associated with higher subjective social status. Additionally, students in the High-level BJW profile exhibited the highest levels of self-regulated learning, even after controlling for gender, residence, class cadre, and parental educational levels.Discussion: These results suggest that subjective social status can enhance Belief in a Just World, which in turn fosters better self-regulated learning skills. The study offers insights into the role of BJW and provides implications for interventions aimed at improving BJW and associated outcomes.Keywords: belief in a just world, self-regulated learning, social status, justice motive theory

Nanan Miao,1,* Tao Jiang,1,* Yuanchao Li,1 Sihong Xue,1 Shilei Hao,2 Chunli Zhou,1 Yujie Gu,1 Ran Li,1 Bo Yu,1 Xiaoqu Duan,1 Wenchao Xu,1 Rupeng Wang,1 Lei Ran1 1Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 2College of Bioengineering, University of Chongqing, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rupeng Wang; Lei Ran, Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 23 68755739, Email Wrp71@tmmu.edu.cn; ranlei1010@tmmu.edu.cnBackground: Wound healing is a complex physiological process that can be roughly divided into four stages: hemostasis, inflammation, proliferation, and remodeling. Conventional wound dressings often fail to meet the diverse needs of these healing stages due to their limited functionality. Cryogels, however, possess several attractive properties, such as large, interconnected pores, good mechanical strength, and ease of modification, making them suitable for developing advanced dressings with multiple functions. In this study, we developed a multifunctional cryogel dressing, with biocompatible polysaccharides as the main component, designed to provide a breathable, moist, and antibacterial microenvironment for chronic infected wounds, thereby promoting wound healing.Methods: Recombinant keratin 31 (RK31) was combined with chitosan (CS) to produce a CS/RK31 cryogel, referred to as CK. Gallic acid-reduced silver nanoparticles (GA/Ag NPs) were incorporated as the active antibacterial component to create the CS/K31@GA/Ag cryogel, known as CKGA. The cryogel was characterized using scanning electron microscopy (SEM) and a universal testing machine, and its biocompatibility was assessed in vitro. The dynamic hemostatic performance of the cryogel was evaluated with a rat tail amputation bleeding model. Additionally, the antibacterial effects of the cryogel against Staphylococcus aureus and Escherichia coli were tested using agar diffusion assays and turbidimetry. The antioxidant capacity of the CKGA cryogel was also measured in vitro. Finally, the cryogel’s ability to promote wound healing was tested in an SD rat model of infected wounds.Results: Characterization results showed that the CKGA cryogel features an interpenetrating porous network structure and exhibits excellent mechanical properties, with a swelling rate of up to 1800%. Both in vitro and in vivo experiments confirmed that the cryogel has good biocompatibility, effectively absorbs exudates, and rapidly stops bleeding. The addition of GA/Ag NPs provided significant antibacterial effects, achieving an inhibition rate of over 99.9% against both S. aureus and E. coli. Furthermore, CKGA cryogels demonstrated a strong scavenging capacity for ROS in a dose-dependent manner. Studies using the SD rat infected wound model showed that the cryogel effectively inhibited bacterial proliferation on wound surfaces, reduced local tissue inflammation, and promoted the healing of infected wounds.Conclusion: The multifunctional cryogel, with its rapid hemostatic, antibacterial, and antioxidant properties, as well as its ability to promote cell proliferation, could be widely used as a wound dressing for the healing of bacterial infections. Keywords: nanocomposite cryogel, hemostasis, antioxidant, antibacterial, wound healing

Jiajia Zhou,1,2,* Shuang Song,2,3,* Senlin Xue,2 Yingxing Zhu,3 Boyin Xu,4 Ping Ma,2,3 Yanguan Lv,1 Haiquan Kang2,3 1The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, People’s Republic of China; 2Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Infection Control, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiquan Kang, Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China, Tel +86-516 85802759, Email hqk811029@163.com Yanguan Lv, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, 223001, People’s Republic of China, Tel +86-517 89687770, Email lvyanguan@163.comBackground: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP’s epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures.Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis.Results: Infants (0– 1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were blaNDM-5 in children (58.1%) and blaKPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 blaKPC-2 and ST15 blaOXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing blaNDM-5 and blaOXA-181 in the NICU.Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.Keywords: children, adults, Klebsiella pneumoniae, carbapenemases, drug resistance mechanisms

Zhipeng Liu,1,&ast; Xinyu Yuan,2,&ast; Yan Huang,3 Zihan Gu,4 Lu Xue,5 Shanshan Xue,6 Jun Wang2 1Information Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 2Emergency Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 3Medical College, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 4Nanjing University of Finance & Economics, Nanjing, 210023, People’s Republic of China; 5Department of Critical Care Medicine, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 6Institute of Clinical Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Shanshan Xue, Email 15061008998@163.com; 245116999@qq.comBackground: Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI.Methods: A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored.Results: As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015– 1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792– 0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032– 1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010– 1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045– 1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035– 1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = − 0.3426, p = 0.0002; r = − 0.3069, p = 0.0008) and AST activity (r = − 0.2483, p = 0.0072; r = − 0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = − 0.5027, p < 0.0001; r = − 0.4218, p < 0.0001), IL-1β (r = − 0.3349, p = 0.0002; r = − 0.4070, p < 0.0001) and IL-6 (r = − 0.2734, p = 0.0030; r = − 0.3536, p < 0.0001), respectively.Conclusion: IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.Keywords: acute liver injury, sepsis, IFIT1, IFIT2, inflammation, Mendelian randomization

Tongchao Jiang,1,&ast; Haishuang Sun,2,&ast; Tiankai Xu,1 Shuyu Xue,1 Wen Xia,2 Xiang Xiao,1 Ying Wang,1 Ling Guo,3 Huanxin Lin1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huanxin Lin, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email linhx@sysucc.org.cn Ling Guo, Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email guoling@sysucc.org.cnBackground: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models.Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis.Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort.Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.Keywords: CALLY score, EBV DNA, nasopharyngeal carcinoma, biomarker, prognostic model

Qianqian Liang,1– 3 Difang Sun,1– 3 Shuyue Xue,1– 3 Xinying Li,1– 3 Xin Liu,1– 3 Qing Du,1– 3 Zhichun Zhang,1– 3 Xiubin Ma,1– 3 Jun Li1– 3 1Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Qingdao, Shandong, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Jun Li; Xiubin Ma, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, People’s Republic of China, Tel +86-532-85876380, Email doctor_li@126.com; maxiubin2005@126.comPurpose: To compare the effectiveness and safety of adjustable and free postoperative positioning after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD).Design: Prospective, randomized controlled study.Methods: A total of 94 eyes with RRD were enrolled from April 2020 to April 2023 and monitored postoperatively for at least 3 months. All patients underwent PPV combined with silicone oil injection or gas tamponade and were randomly divided postoperatively into two groups: an adjustable positioning group and a free positioning group. The success of the outcome was based on the retinal reattachment rate, best corrected visual acuity (BCVA), postoperative complications, and ocular biometric parameters such as anterior chamber depth (ACD) and lens thickness (LT).Results: The initial retinal reattachment rate was 97.9% in the adjustable positioning group and 95.7% in the free positioning group, manifesting no statistical difference between the two groups. Similarly, no statistical difference was observed between the two groups in the final BCVA, which was significantly improved compared to the preoperative BCVA. The comparison of the 1-month postoperative ACD and LT with the preoperative values showed no statistically significant differences in the two groups. The rates of complications were not statistically different in the two groups.Conclusion: After treating RRD using PPV, neither the adjustable nor the free postoperative positioning affected the retinal reattachment rate or the incidence of complications. Therefore, our study showed that it is safe and effective to adopt free positioning postoperatively, which may provide more options for patients with RRD undergoing PPV.Keywords: rhegmatogenous retinal detachment, pars plana vitrectomy, adjustable positioning, free positioning

Fenglei Wang, Zhiying Yu, Shasha Xue, Yunxiao Wang, Lin Li, Dabo Wang, Ling Wang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Ling Wang, Department of Ophthalmology, the Affiliated Hospital of Qingdao University, University, No. 16 Jiangsu Road, Shinan District, Qingdao, 266003, People’s Republic of China, Tel +86 18661806679, Email tsingtaowl@hotmail.comPurpose: To investigate the differences in parameters related to angle configuration and lens position in patients with cortical age-related cataract by ultrasound biomicroscopy (UBM) in different body positions.Methods: Prospective study with 55 patients with cortical age-related cataract proposed for phacoemulsification, examined using a Compact Touch STS UBM (Quantel Medical, France). UBM bag/balloon technology was applied to measure the central anterior chamber depth (ACD) and lens vault (LV) in horizontal and vertical orientation in sitting and supine positions, angle opening distance (AOD500), trabecular iris angle (TIA) and iris lens angle (ILA) in four quadrants: superior, inferior, nasal, and temporal.Results: We found no significant difference in ACD between sitting and supine positions (p = 0.053); LV was significantly greater in the supine position (p < 0.001); AOD500 in superior and inferior quadrants were significantly longer in the sitting position (p = 0.001; p < 0.001); TIA in superior and inferior quadrants was significantly greater in the sitting position (p < 0.001; p < 0.001), and TIAmax-min was significantly smaller in the sitting position (p = 0.001); ILA in temporal quadrant was significantly larger in the sitting position (p = 0.015) and ILAmax-min was significantly smaller in the sitting position (p < 0.001).Conclusion: The anterior chamber angle was narrower and the lens was positioned more anteriorly in the supine than in the sitting position in cortical age-related cataract. Different positions may affect the angle configuration and the relative space of lens through different directions of mechanics and modes of action.Keywords: angle configuration, body position, ultrasound biomicroscopy, cortical age-related cataract

Yan Li,1,2 Xiaopeng Chen,1,3 Rujuan Zhou,2 Wu Xu,2 Xiaorong Wang,2 Wa Chao,1 Shouru Xue1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The Taixing People’s Hospital, Taixing, People’s Republic of China; 3Department of Neurology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Shouru Xue, Department of Neurology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, 215006, People’s Republic of China, Tel +86-18962133036, Fax +86-512-65223637, Email xueshouru@suda.edu.cnPurpose: This study aimed to investigate the relationship between cognitive impairment and homocysteine (Hcy) and S100B protein in patients with progressive ischemic stroke (PIS).Patients and Methods: A total of 158 patients with PIS hospitalized in the Department of Neurology in Taixing People’s Hospital from January 2020 to March 2022 were enrolled in the study. After 90 days of follow-up, the patients were divided into two groups according to the MoCA score— 99 cases with cognitive impairment group (observation group) and 59 cases with cognitive normal group (control group). Causal diagram was drawn to assess the association between risk factors and PIS with observation group. The risk factors indicators of cognitive impairment in patients with PIS were screened. The related predictive indicators were screened by multivariate logistic regression analysis, and Pearson correlation analysis. The predictive value was analyzed by Receiver Operating Characteristic (ROC) curve.Results: Multivariate logistic regression analysis showed that age, hypertension, lesion position, Hcy and S100B protein were related risk factors for cognitive impairment in patients with PIS. Pearson correlation analysis was conducted between Hcy and S100 B protein and MoCA score, and revealed that Hcy and S100 B protein were negatively correlated with MoCA score. ROC curve analysis showed that the Area Under the Curve (AUC) of S100 B protein and Hcy in identifying cognitive impairment after PIS was 0.709 and 0.673, respectively, and the combined AUC of Hcy and S100B protein in predicting cognitive impairment after PIS was 0.739.Conclusion: Hcy and S100B protein are related risk factors for cognitive impairment in patients with PIS, and may be used as in a prediction model to predict cognitive impairment after PIS in the future.Keywords: progressive ischemic stroke, cognitive impairment, homocysteine, S100B protein

Shuang Xue,1,2 Michelle R Kaufman,3 Xing Zhang,4 Shunan Xia,5 Chengcheng Niu,6 Rui Zhou,7 Wenjian Xu1,2 1Department of Sociology & Psychology, School of Public Administration, Sichuan University, Chengdu, People’s Republic of China; 2Institute of Psychology, Sichuan University, Chengdu, People’s Republic of China; 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 4School of Psychology, Jiangxi Normal University, Nanchang, People’s Republic of China; 5School of Social Development and Public Policy, Fudan University, Shanghai, People’s Republic of China; 6Faculty of Psychology, Southwest University, Chongqing, People’s Republic of China; 7College of Marxism, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wenjian Xu; Rui Zhou, Email xuwenjian@scu.edu.cn; ruizhou_283@163.comPurpose: Suffering during events such as the COVID-19 pandemic threatens university students’ physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation.Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior.Results: Pearson’s correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students’ prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts.Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students’ prosocial behavior.Keywords: COVID-19, resilience, social support, prosocial behavior, mediation and moderation

Xiaopeng Chen,1,2 Guoqiang Ren,3 Yan Li,1,4 Wa Chao,1 Siyuan Chen,2 Xuezhong Li,2 Shouru Xue1 1Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Neurology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Radiology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Department of Neurology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of ChinaCorrespondence: Shouru Xue, Department of Neurology, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, Jiangsu Province, 215006, People’s Republic of China, Tel +86-18962133036, Fax +86-512-65223637, Email xueshouru@suda.edu.cnPurpose: We evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer’s disease (AD).Patients and Methods: One hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman’s rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD.Results: The levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%.Conclusion: The results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.Keywords: Alzheimer’s disease, long non-coding RNA, receiver operating characteristic, biomarker

Wei Tang,1,&ast; Qian Lv,1,&ast; Xiao Huang,2,&ast; Yuzhen Li,2 JunJie Zou,1 Jiaoyang Zheng,1 Liangliang Sun,1 Yi Bao,1 Haiyan Chen,1 Tuo Li,1 Bei Zhang,1 Song Xue,1 Yan Song,1 Xingxing Zhang,1 Xiangfang Chen,1 Jiping Cai,2 Yongquan Shi1 1Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfang Chen; Yongquan Shi, Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, People’s Republic of China, Email chenxiangfang@smmu.edu.cn; young.stone@smmu.edu.cnObjective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation.Methods: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice.Results: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO.Conclusion: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.Keywords: thyroid-associated ophthalmopathy, miR-143, thyroid-stimulating hormone receptor, insulin-like growth factor 1 receptor, NLRP3

Li Gu,1 Song Xue2 1Department of Endocrinology, People’s Hospital of Gaochun, Nanjing, 211300, People’s Republic of China; 2Department of Pathology, People’s Hospital of Gaochun, Nanjing, 211300, People’s Republic of ChinaCorrespondence: Li GuDepartment of Endocrinology, People’s Hospital of Gaochun, No. 53 Maoshan Road, Gaochun District Economic Development Zone, Nanjing, 211300, People’s Republic of ChinaTel +86 13851529447Email Rougu_doct@163.comPurpose: Red cell distribution width (RDW) has been evidenced to be related to various diabetes-associated macrovascular and microvascular complications. However, the studies on the association between RDW and diabetic chronic kidney disease (CKD) are still scarce. The aim of the study is to explore whether there is any association between RDW and the severity of diabetic CKD.Patients and Methods: The study recruited 396 patients diagnosed with diabetic CKD at People’s Hospital of Gaochun from January 2006 to April 2021. Baseline characteristics were gathered and laboratory tests were performed to measure clinical indexes. Patients were also categorized into three groups based on their CKD stages. Correlation analysis and multivariate ordinal logistic regression were performed to investigate the association between RDW and the severity of diabetic CKD. The risk size was described as odds ratio (OR) and 95% confidence interval (CI).Results: We found a significant association between RDW and the severity of CKD, with a correlation coefficient of 0.32 (P < 0.01). We used three models for multivariate ordinal logistic regression to investigate the relationship between RDW and the severity of CKD. Results showed that RDW is an independent and significant risk factor of diabetic CKD after adjustment for demographic data, physiological indexes, and drug history [Model 3 OR (95% CI) = 1.225 (1.023– 1.467)]. In subgroup analysis, RDW remained a significant risk factor in all three models for patients who had diabetes of 5– 10 years [Model 3 OR (95% CI) = 1.480 (1.067– 2.052)] and had a HbA1c level > 7% [(Model 3 OR (95% CI) = 1.478 (1.184– 1.845)].Conclusion: RDW is significantly associated with the disease stages of diabetic CKD, and the risk is higher for people with 5– 10 years of diabetes and for those who do not control the HbA1c level well. This study has implications for the diagnosis, monitoring, and timely treatment of the diabetic CKD.Keywords: red cell distribution width, diabetic chronic kidney disease, correlation, inflammation

Sijia Ma,1 Mingming Zhao,1 Jiao Fan,1 Meiying Chang,1 Zhiyu Pan,1 Ziyan Zhang,1 Shunxuan Xue,1 Qi Li,2 Yu Zhang1 1Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yu Zhang Email zhangyu8225@126.comIntroduction: Renal clear cell carcinoma (ccRCC) is a common tumor of the urinary system, most of which are primary malignant tumors with high metastatic rate and remaining incurable. Ferroptosis is a newly discovered form of iron-dependent programmed cell necrosis in recent years, which is inextricably linked to the occurrence and development of tumors progression. Due to the complexity of the interaction between genes in ccRCC, the research on the pathogenesis of ccRCC is still not remarkably accurate. Therefore, whether ferroptosis-related genes (FRGs) can play a role in predicting prognosis in ccRCC needs to be discussed.Methods: We entered the Cancer Genome Mapping Project (TCGA) database and downloaded the relevant genes and clinical research data of ccRCC patients. Lasso Cox regression was used to construct a multi-gene prognostic model in the TCGA cohort. R language software was used for drawing pictures related to our study.Results: Most of the genes involved in ferroptosis (86.2%) existing differences between the tumor and normal tissues in the TCGA public gene database. In terms of univariate Cox regression analysis, 20 differentially expressed genes (DEGs) were associated with prognosis and survival (P< 0.05). A prognostic model of 12 FRGs was constructed, and patients were segmented into two different groups depending on how risky they are. Considering overall survival, the high-risk group is dramatically lower than the low-risk group (P< 0.001). In multivariate Cox regression analysis, risk scores and stage turned out be an independent prognostic factor (P< 0.001). GO and KEGG analysis and ssGSEA analysis of DEGs revealed that these genes were related to immune-related pathways (P< 0.05).Conclusion: This study established and identified the changes in FRGs expression and prognostic factors of ccRCC, which can be helpful for prognosis evaluation and clinical treatment of this disease.Keywords: renal clear cell carcinoma, ferroptosis, TCGA database, the prognosis

Guomei Shi,1,2,&ast; Wenxiu Chen,3,&ast; Pengyu Gong,4 Meng Wang,4 Junshan Zhou,4 Xiaorong Wang,1 Minwang Guo,1 Jingye Lu,1 Yan Li,1 Hongxuan Feng,2,5 Xuetao Fu,2,6 Rujuan Zhou,1 Shouru Xue2 1Department of Neurology, The Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, People’s Republic of China; 6Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rujuan Zhou; Shouru Xue Tel +86-13951158499; +86-18962133036Email zhourujuan123@163.com; xueshouru@suda.edu.cnBackground: Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7– 38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP.Methods: Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP.Results: Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (P=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%.Conclusion: Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.Keywords: acute ischemic stroke, YKL-40, stroke-associated pneumonia

Lei Yang, Song Xue, Mingjun Du, Feng Lian Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Feng Lian Email dr.lianfeng@hotmail.comIntroduction: The reprogramming of induced cardiomyocytes (iCMs) is of particular significance in regenerative medicine; however, it remains a great challenge to fabricate an efficient and safe gene delivery system to induce reprogramming of iCMs for therapeutic applications in heart injury. Here, we report branched polyethyleneimine (BP) coated nitrogen-enriched carbon dots (BP-NCDs) as highly efficient nanocarriers loaded with microRNAs-combo (BP-NCDs/MC) for cardiac reprogramming.Methods: The BP-NCDs nanocarriers were prepared and characterized by several analytical techniques.Results: The BP-NCDs nanocarriers showed good microRNAs-combo binding affinity, negligible cytotoxicity, and long-term microRNAs expression. Importantly, BP-NCDs/MC nanocomplexes led to the efficient direct reprogramming of fibroblasts into iCMs without genomic integration and resulting in effective recovery of cardiac function after myocardial infarction (MI).Conclusion: This study offers a novel strategy to provide safe and effective microRNAs-delivery nanoplatforms based on carbon dots for promising cardiac regeneration and disease therapy.Keywords: nitrogen-enriched carbon dots, branched polyethyleneimine, microRNAs, direct reprogramming, induced cardiomyocytes

Sufang Xue,1,* Yi Yang,1,* Pengyu Li,2 Ping Liu,3 Xiangying Du,2 Xin Ma1 1Neurology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Radiology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Neurology Department of Hejian People’s Hospital, Cangzhou, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin MaNeurology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-135-0139-0691Email maxin118@hotmail.comObjective: Vertebral artery dissection (VAD) combined with congenital craniovertebral junction malformation (CVJM) is rare. This study aimed to analyze the etiology, clinical and imaging features, treatment, and prognosis of VAD with CVJM.Methods: Four new cases of VAD with congenital CVJM and 28 similar cases found in the literature were included. Detailed clinical data from all cases were retrospectively analyzed.Results: A total of 32 patients (28 men, four women; mean age 19.01± 12.53 years) were included. Seventeen of 32 cases (53.1%) had had multiple ischemic episodes. The most common neurological symptoms were limb numbness/weakness (20/32), ataxia (15/32), and dizziness/vertigo (12/32). In sum, 31 of 32 cases had multiple infarcts scattered throughout the posterior circulation area on cranial computed tomography or resonance imaging. Dissection had occurred in the V3 segment of the VA in 29/31 cases (93.5%). The most common congenital CVJMs were atlantoaxial dislocation and atlantoaxial subluxation (found in 20/32 cases [62.5%]), while 27/32 cases (84.3%) had multiple combined abnormalities. Seven of eleven cases (63.6%) with initial antiplatelet treatment and one of eleven (9.1%) with initial anticoagulation treatment experienced stoke recurrence. Fusion or vertebral fixation was performed in 16 patients and aneurysm resection in one patient. There was no reported recurrence after surgery in 13 patients with follow-up data.Conclusion: Underlying CVJM is a rare but overlooked etiology in VAD, and is prone to induce recurrent ischemic stroke. Patients with VAD, especially that localized in the V3 segment, should be examined for CVJM. Timely assessment is critical for determining the specific cause and to provide targeted intervention.Keywords: vertebral artery dissection, craniovertebral junction malformation, clinical and imaging features, treatment, prognosis

Background: Red-skin root of Asian ginseng (Panax ginseng) significantly reduces the quality and limits the production of ginseng in China. The disease has long been thought to be a noninfectious physiological disease, except one report that proved it was an infectious disease. However, the causal agents have not been successfully determined. In the present study, we were to reveal the pathogens that cause red-skin disease. Methods: Ginseng roots with red-skin root symptoms were collected from commercial fields in Northeast China. Fungi were isolated from the lesion and identified based on morphological characters along with multilocus sequence analyses on internal transcription spacer, β-tubulin (tub2), histone H3 (his3), and translation elongation factor 1α (tef-1α). Pathogens were confirmed by inoculating the isolates in ginseng roots. Results: A total of 230 isolates were obtained from 209 disease samples. These isolates were classified into 12 species, including Dactylonectria sp., D. hordeicola, Fusarium acuminatum, F. avenaceum, F. solani, F. torulosum, Ilyonectria mors-panacis, I. robusta, Rhexocercosporidium panacis, and three novel species I. changbaiensis, I. communis, and I. qitaiheensis. Among them, I. communis, I. robusta, and F. solani had the highest isolation frequencies, being 36.1%, 20.9%, and 23.9%, respectively. All these species isolated were pathogenic to ginseng roots and caused red-skin root disease under appropriate condition. Conclusion: Fungal complex is the causal agent of red-skin root in P. ginseng. Keywords: Cylindrocarpon, Fusarium, Ilyonectria, Panax ginseng, Root disease

Minmin Yu,1,2,* Baozhen Xu3,*, Hui Yang4,*, Songlin Xue,2 Rong Zhang,2 Hongmei Zhang,5 Xiaoyan Ying,1 Zhiqin Dai61Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing Lishui People’s Hospital, Nanjing 211200, People’s Republic of China; 4Department of Obstetrics and Gynecology, Huaian Maternal and Child Health Care Hospital, Huaian 223002, People’s Republic of China; 5Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 6Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing 210009, People’s Republic of China*These authors contributed equally to this workBackground: Cervical cancer is one of the most lethal malignancies among women in the world. Every year about 311,365 women die because of cervical cancer. Chemo-resistance is the main reason of the lethal malignancies, and the mechanism of chemo-resistance in cervical cancer still remains largely elusive.Purpose: Previous studies reported that microRNAs played important biological roles in the chemo-resistance in many types of cancers, in the present study we tried to investigate the biological roles of microRNA-218 in chemo-resistance in cervical cancer cells.Results: Real-time PCR results indicated microRNA-218 was downregulated in cisplatin-resistant HeLa/DDP and SiHa/DDP cells compared with the mock HeLa and SiHa cells. CCK-8 assay results showed upregulation of microRNA-218 enhanced the cisplatin sensitivity of cervical cancer cells; while downregulation of microRNA-218 decreased the cisplatin sensitivity of cervical cancer cells. Dual-luciferase assay indicated survivin was a direct target of microRNA-218. Western blotting and PCR results indicated the expression of survivin in HeLa/DDP and SiHa/DDP cells was significantly increased compared with HeLa and SiHa cells. Further study indicated induction of microRNA-218 decreased the expression of survivin while inhibition of microRNA-218 increased the expression of survivin in cervical cancer cells. Cell apoptosis results indicated induction of microRNA-218 induced the cell apoptosis in cervical cancer cells.Conclusion: Our data revealed microRNA-218 enhanced the cisplatin sensitivity in cervical cancer cells through regulation of cell growth and cell apoptosis, which could potentially benefit to the cervical cancer treatment in the future.Keywords: miR-218, cervical cancer, cisplatin resistant, apoptosis, survivin

Jinming Li,* Yuanyuan Wang,* Shanshan Xue, Jinghua Sun, Wei Zhang, Ping Hu, Liangnian Ji, Zongwan Mao MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: In recent years, lung cancer has become one of the fastest growing cancers in the world. Thus, the development of efficient combination therapy to treat lung cancer has attracted significant attention in the cancer therapy field. In this article, we developed a single vehicle drug delivery system, based on quantum dot (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and different anticancer drugs (carboplatin, paclitaxel, and doxorubicin) simultaneously for treating A549 lung cancer cells efficiently by combination therapy. The QD nanoparticles were conjugated with L-arginine (L-Arg) and different kinds of hydroxypropyl-cyclodextrins (HP-α-CDs, HP-β-CDs, and HP-γ-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers). They were able to not only bind and transport the siRNA through electrostatic interactions with L-Arg residues but also accommodate various disparate anticancer drugs using different HP-CD modifications. Compared with free drug treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different anticancer drugs simultaneously exerted a threefold to fourfold increase in cytotoxicity in A549 cells, which greatly improved the treatment efficacy through combined action. Furthermore, the QD nanocarriers could be used as a probe for real-time imaging of the drug delivery and release because of their strong fluorescence properties. These findings indicate that multifunctional QD nanocarriers hold great promise as a powerful tool for combination therapy for lung cancer. Keywords: combination therapy, lung cancer cells, Bcl-2 siRNA, anticancer drugs, quantum dot nanocarriers

Sihan Xue,1 Yao Wang,1 Mengxing Wang,2 Lu Zhang,1 Xiaoxia Du,2 Hongchen Gu,1 Chunfu Zhang1,31School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 2Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, 3State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaAbstract: In this study, a novel magnetic resonance imaging (MRI)/computed tomography (CT)/fluorescence trifunctional probe was prepared by loading iodinated oil into fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (i-fmSiO4@SPIONs). Fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) were prepared by growing fluorescent dye-doped silica onto superparamagnetic iron oxide nanoparticles (SPIONs) directed by a cetyltrimethylammonium bromide template. As prepared, fmSiO4@SPIONs had a uniform size, a large surface area, and a large pore volume, which demonstrated high efficiency for iodinated oil loading. Iodinated oil loading did not change the sizes of fmSiO4@SPIONs, but they reduced the MRI T2 relaxivity (r2) markedly. I-fmSiO4@SPIONs were stable in their physical condition and did not demonstrate cytotoxic effects under the conditions investigated. In vitro studies indicated that the contrast enhancement of MRI and CT, and the fluorescence signal intensity of i-fmSiO4@SPION aqueous suspensions and macrophages, were intensified with increased i-fmSiO4@SPION concentrations in suspension and cell culture media. Moreover, for the in vivo study, the accumulation of i-fmSiO4@SPIONs in the liver could also be detected by MRI, CT, and fluorescence imaging. Our study demonstrated that i-fmSiO4@SPIONs had great potential for MRI/C/fluorescence trimodal imaging.Keywords: multifunctional probe, SPIONs, mesoporous silica, iodinated oil

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.