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Chengshuai Zhang,1,2,&ast; Juan Xu,1,&ast; Tingting Dong,1 Xin Gai,1 Hongmei Zhang,1 Yuanyuan Li1 1Department of Neurorehabilitation, Sheng Li Oilfield Central Hospital, Dongying, People’s Republic of China; 2Binzhou Medical University, Binzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Li, Department of Neurorehabilitation, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying, 257000, People’s Republic of China, Tel +86-18562058575, Email 15754308875@163.comBackground: This study aimed to examine the blood concentrations of selected heavy metals, their corresponding pulmonary functions, and their interrelationship with university students.Methods: This prospective study, conducted from September 2019 to September 2020, encompassed 593 university students. Participants completed self-administered questionnaires regarding demographic factors and underwent lung function testing and blood mercury analysis at two distinct intervals: an initial assessment and a follow-up examination. Pulmonary function was assessed using Forced Vital Capacity, Forced Expiratory Volume in one second, and Peak Expiratory Flow. The blood concentrations of various heavy metals were determined through inductively coupled plasma mass spectrometry.Results: Notable disparities in pulmonary function emerged among university students when categorized by gender, Body Mass Index, physical activity, and seafood consumption frequency, all showing statistical significance (p< 0.05). Blood levels of Pb, Mn, Co, and Ni exhibited diverse patterns and extents of correlation with pulmonary function (p< 0.05 in each instance). Specifically, a positive correlation was observed with blood Pb levels, while Mn, Co, and Ni levels were inversely correlated with pulmonary function (p< 0.01 for both observations).Conclusion: This study uncovered significant and complex relationships between the blood concentrations of individual heavy metals and pulmonary function in university students. These findings highlight the need for further research to elucidate these associations in greater detail.Keywords: heavy metal, pulmonary function, students

Zhihan Jiang,1,&ast; Yingying Dai,2,&ast; Jing Chang,2 Pingchao Xiang,3 Zhenyu Liang,4 Yan Yin,5 Yongchun Shen,6 Ruiying Wang,7 Bianba Qiongda,8 Hongling Chu,9 Nan Li,9 Xiaoyan Gai,1,10 Ying Liang,1,10 Yongchang Sun1,10 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, GuangZhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 9Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 10Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 13810964766 ; +86 13910979132, Fax +86 108 226 6989, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation.Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred.Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.Keywords: chronic obstructive pulmonary disease, COPD, pulmonary tuberculosis, tuberculosis-associated COPD, protocol

Xiaojing Wu,1,2 Xiaosong Gai,1,2 Hongyang Kou,3 Lili Xu,1 Fangqing Liu,4 Hong Wang1 1School of Psychology, Northeast Normal University, Changchun, Jilin Province, People’s Republic of China; 2Research Center of Mental Health Education in Northeast Normal University, Key Research Institute of Humanities and Social Science in Universities in Jilin Province, Changchun, Jilin Province, People’s Republic of China; 3Northeast Asian Studies College, Jilin University, Changchun, Jilin Province, People’s Republic of China; 4Institute of Mental Health, NanJing Xiaozhuang University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xiaosong Gai, School of Psychology, Northeast Normal University, No. 5268, Renmin Street, Changchun, Jilin Province, People’s Republic of China, Email gaixs669@nenu.edu.cnPurpose: Life satisfaction can predict students’ school engagement and academic performance, and has shown significant regional differences among adolescents. The predictive effect of economic factors as regional characteristics on adolescent life satisfaction has been extensively examined; however, the regional educational factors that could predict adolescent life satisfaction remain unknown. This study aimed to identify provincial-level educational factors that can predict adolescent life satisfaction.Methods: The participants comprised 16,737 students, aged 11– 16 years (Mage = 13.82; SDage = 0.77; 8767 girls, 7970 boys), from 31 provinces in China. Students completed measures on socioeconomic status and life satisfaction. Multilevel modeling was adopted in data analysis.Results: Adolescent life satisfaction was positively correlated with family socioeconomic status, and negatively associated with age and academic ranking. Life satisfaction was lower for girls than boys. Some regional education development indicators could predict adolescent life satisfaction: ratio of students to teachers, ratio of students to teachers with master’s degrees, and multimedia classroom size negatively correlated with adolescent life satisfaction; meanwhile per capita sports field area positively correlated with adolescent life satisfaction. Per capita education expenditure, classroom area, laboratory area, computer room area, language lab area, gymnasium area, green space area, sports field area, computers per student, number of books, and value of equipment and instruments could not significantly predict life satisfaction in this study.Conclusion: The findings suggest that the life satisfaction of female adolescents, those in older age groups, with lower academic rankings and socioeconomic status, and those residing in regions with underdeveloped educational systems was relatively poor. These groups of adolescents should therefore be given special attention. To enhance their life satisfaction, some certain provinces should consider implementing measures such as increasing the number of teachers, reducing class sizes, and providing more opportunities for physical activity among junior middle school students.Keywords: provincial-level, junior middle school students, life satisfaction, education, ecological systems theory

Ke Yin,1 Qiong Wu,2 Xiaosong Gai1 1School of Psychology, Northeast Normal University, Changchun, People’s Republic of China; 2Faculty of Education, Northeast Normal University, Changchun, People’s Republic of ChinaCorrespondence: Qiong Wu, Tel +86 13504314652, Fax +86 85683180, Email wuq936@nenu.edu.cnPurpose: The purpose of this study was to examine differences between directly measured and parent-evaluated executive function in predicting children’s academic achievement and social development, and to explore the mediating roles of peer status and social competence in the effects of executive function on social behavior.Patients and Methods: The study followed 106 first-grade children in an elementary school in China for one year. Regression and mediation analyses were conducted using SPSS 26.0 and AMOS 21.0 to test the hypotheses.Results: First, in a comparison of the predictive role of directly measured and parent-evaluated executive function, directly measured executive function played a more important role in predicting academic achievement, while parent-evaluated executive function played a greater role in predicting social development. Second, parent-evaluated executive function influenced social behavior primarily through social competence and peer status, with social competence playing a more significant mediating role than peer status.Conclusion: Compared with previous studies, the results of the present study provide more direct evidence for the relationship and differences between directly measured and parent-evaluated executive function, further suggesting that they have different efficacy and predictive goals, while the present study also describes the pathways through which executive function influences social behavior: the mediating role of peer status and social competence. This suggests that, on the one hand, educators or researchers need to choose appropriate measures of executive function for their own purposes and, on the other hand, in order to promote the development of children’s social behavior, they need to focus on the development of children’s executive function, social competence and peer relationships.Keywords: peer status, social behavior, social competence, cognitive control, measurement

Dannuo Lyu,1 Xiaosong Gai,1,2 Yanfeng Zhong3 1School of Psychology, Northeast Normal University, Changchun, Jilin Province, People’s Republic of China; 2Research Center of Mental Health Education in Northeast Normal University, Key Research Institute of Humanities and Social Science in Universities in Jilin Province, Changchun, Jilin Province, People’s Republic of China; 3Changchun Sixth Hospital, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Xiaosong Gai, Northeast Normal University, Nanling Street, Changchun City, Jilin Province, 130024, People’s Republic of China, Tel +86 186 4307 2597, Email gaixs669@nenu.edu.cnPurpose: Although previous studies have confirmed that purpose in life may negatively predict depressive symptoms, focusing on the intensity of purpose without focusing on content may ignore significant individual differences. This study explores differences in purpose orientations between depressive patients and healthy population to examine the relationship between the purpose content and self-esteem, one of the symptoms of depression. In addition, the moderating role of purpose orientations in the relationship between depression and self-esteem was analyzed to verify the protective effect of purpose orientation on self-esteem.Patients and Methods: The study utilized the questionnaire approach. The Purpose Orientation Scale (Self and Forced Rating) and the Rosenberg Self-Esteem Scale were administered to the participants. The study recruited 73 depressive patients using convenience sampling. Moreover, using random sampling, 146 participants matched based on depressive patients’ demographics were selected as a healthy population in a 1:2 ratio.Results: The results showed that: 1) depressive patients valued all four types of purpose orientations to a lesser extent compared to healthy population, both depressive patients and healthy population valued family well-being and personal growth to a greater extent than personal well-being and social promotion. 2) Depressive patients reported lower self-esteem than healthy people. 3) All four types of Purpose orientations positively correlated with self-esteem in depressive patients, while only personal well-being positively correlated with self-esteem in healthy population. Family well-being and social promotion moderated the predictive effect of depression on self-esteem.Conclusion: The above results imply that prosocial purpose orientations may attenuate the harmful effects of depression on self-esteem. Additionally, intervention focusing on enhancing depressive patients’ purpose in life (especially prosocial purpose) could be helpful.Keywords: purpose in life, meaning in life, self-esteem, hopelessness, prosocial

Hong Wang,1 Xiaosong Gai,1,2 Songliang Li1 1School of Psychology, Northeast Normal University, Changchun, Jilin Province, People’s Republic of China; 2Research Center of Mental Health Education in Northeast Normal University, Key Research Institute of Humanities and Social Science in Universities in Jilin Province, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Xiaosong Gai, School of Psychology, Northeast Normal University, No. 5268, Renmin Street, Changchun, Jilin Province, People’s Republic of China, Email gaixiaosong@126.comIntroduction: Purpose orientation has an important impact on the development of adolescence. An effective instrument is needed to describe the purpose orientation of youth. The aim of this research is to develop a reliable and valid scale to measure life purpose orientations of youth.Methods: Study 1 established a preliminary pool of items based on a literature review, an open-form questionnaire, and some expert opinions. Study 2 used exploratory factor analysis and performed internal consistency and reliability tests. The sample consisted of 442 young Chinese students, divided into males (49.3%) and females (50.7%) with an age range of 13 to 22 years. Study 3 performed confirmatory factor analysis and tested the scale’s calibration validity and test-retest reliability. The confirmatory sample comprised 91,635 young Chinese students, divided into males (43.2%) and females (56.5%) with an age range of 12 to 23 years. The calibration validity sample consisted of 572 participants, aged 12 to 22. The test-retest reliability sample consisted of 200 participants.Results: Through exploratory factor analysis, the four-factor structure revealed contains personal growth, social promotion, family well-being, and personal well-being purpose orientations. This four factor-structure revealed a 65.26% cumulative variance. The four factors’ alpha reliability was 0.89 for personal growth, 0.87 for social promotion, 0.86 for family well-being, and 0.87 for personal well-being, respectively. Confirmatory factor analysis showed that the model fitting index had a good four-factor structure. The calibration validity and test-retest reliability were acceptable.Conclusion: These findings demonstrated that the 19-item findings demonstrated that the Youth Purpose Orientation Scale is a valid and reliable measure. In future research, it can be used to measure purpose orientation in youth.Keywords: purpose, purpose orientation, youth, factor analysis

Danyang Li,1 Tong Wang,2 Qianli Ma,3 Lu Zhou,1 Yanqing Le,1 Yafei Rao,1 Liang Jin,1 Yuqiang Pei,1 Yaning Cheng,4 Chen Huang,5 Xiaoyan Gai,1 Yongchang Sun1 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Thoracic Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 5Center of Basic Medical Research, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xiaoyan Gai; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email gxy81wfl79@163.com; suny@bjmu.edu.cnBackground: It has been reported that a disintegrin and metalloproteinase 9 (ADAM9) is involved in the pathogenesis of cigarette smoke (CS)-associated chronic obstructive pulmonary disease (COPD). But how CS exposure leads to upregulation of ADAM9 remains unknown.Methods: Patients who underwent lobectomy for a solitary pulmonary nodule were enrolled and divided into three groups: non-smokers with normal lung function, smokers without COPD and smoker patients with COPD. Immunoreactivity of interleukin (IL)-17A and ADAM9 in small airways and alveolar walls was measured by immunohistochemistry. Wild-type and Il17a−/− C57BL/6 mice were exposed to CS for six months, and ADAM9 expression in the airway epithelia was measured by immunoreactivity. In addition, the protein and mRNA expression levels of IL-17A and ADAM9 were assessed in CS extract (CSE) and/or IL-17A-treated human bronchial epithelial (HBE) cells.Results: The immunoreactivity of ADAM9 was increased in the airway epithelia and alveolar walls of patients with COPD compared to that of the controls. The expression of IL-17A was also upregulated in airway epithelial cells of patients with COPD and correlated positively with the level of ADAM9. The results from the animal model showed that Il17a−/− mice were protected from emphysema induced by CS exposure, together with a reduced level of ADAM9 expression in the airway epithelia, suggesting a possible link between ADAM9 and IL-17A. Consistently, our in vitro cell model showed that CSE stimulated the expression of ADAM9 and IL-17A in HBE cells in a dose- and time-dependent manner. Recombinant IL-17A induced ADAM9 upregulation in HBE cells and had a synergistic effect with CSE, whereas blocking IL-17A inhibited CSE-induced ADAM9 expression. Further analysis revealed that IL-17A induced c-Jun N-terminal kinase (JNK) phosphorylation, thereby increasing ADAM9 expression.Conclusion: Our results revealed a novel role of IL-17A in CS-related COPD, where IL-17A contributes to ADAM9 expression by activating JNK signaling.Keywords: chronic obstructive pulmonary disease, a disintegrin and metalloproteinase 9, interleukin-17A, airway epithelium

Mingyu Gu,1,2,&ast; Yi Lin,2,&ast; Xianying Gai,3,&ast; Xiaohui Wei,2 Chunhua Lu,4 Yufan Wang,2 Xiaoying Ding,2,&ast; Yongde Peng,1,2 Yuhang Ma2 1Department of Endocrinology and Metabolism, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China; 2Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Endocrinology, Shanghai Sijing Hospital, Shanghai, 201601, People’s Republic of China; 4Community Health Service Center of Sijing, Shanghai, 201601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongde Peng, Department of Endocrinology and Metabolism, Shanghai General Hospital of Nanjing Medical University, 100 Haining Road, Shanghai, 200080, People’s Republic of China, Email pengyongde0908@126.com Yuhang Ma, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, People’s Republic of China, Email mayuhang5992@163.comObjective: To explore the relationship between the level of fatty acid-binding protein 4 (FABP4) and reversion from prediabetes to normal glucose tolerance (NGT).Methods: A two-year retrospective cohort study was conducted on 398 participants with complete information. These 398 participants were divided into an NGT group and an abnormal glucose metabolism (AGM) group after 2 years of follow-up. The baseline level of FABP4 was determined, and the role of FABP4 in predicting reversion from prediabetes to NGT was investigated using an unconditional logistic regression model.Results: Over the two-year follow-up period, 37.4% (149/398) of the participants reverted from prediabetes to NGT. The participants with AGM had a higher baseline level of FABP4 than those with NGT. The baseline level of FABP4 was significantly negatively correlated with reversion from prediabetes to NGT. After adjusting for age, sex, body mass index and waist-to-hip ratio, the level of fasting blood glucose (FBG) [odds ratio (OR) 0.336, 95% confidence interval (CI) (0.196– 0.576)], 2-h post-challenge blood glucose (2hBG) [OR 0.697, 95% CI (0.581– 0.837)], and FABP4 [OR 0.960, 95% CI (0.928– 0.993)] at baseline were significant independent predictors of reversion from prediabetes to NGT. The area under the curve (AUC) value of the receiver operating characteristic curve for FABP4 was 0.605 (95% CI: 0.546– 0.665), and the AUC for FABP4 combined with FBG and 2hBG was 0.716 (95% CI: 0.663– 0.769).Conclusion: A higher baseline level of FABP4 was positively correlated with an adverse profile of diabetes risk factors and negatively correlated with reversion from prediabetes to NGT. FABP4, FBG and 2hBG were predictors of reversion from prediabetes to NGT.Keywords: fatty acid-binding protein 4, FABP4, prediabetes, normal glucose tolerance, abnormal glucose metabolism

Lu Zhou,1 Yanqing Le,1 Jieyu Tian,2 Xia Yang,2 Rong Jin,3 Xiaoyan Gai,1 Yongchang Sun1 1Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China; 2Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 3Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China Background and purpose: Cigarette smoke (CS) induces alveolar destruction through overproduction of proteinases including matrix metalloproteinase (MMP)-9 by alveolar macrophages (AMs). Receptor activator of nuclear factor-κB ligand (RANKL) functions in immune regulation and cytokine secretion; whether it is involved in CS-induced MMP-9 expression is unknown. The purpose of our study was to investigate the expression and functional role of RANKL pathway in MMP-9 production pertaining to the pathogenesis of COPD. Materials and methods: We first localized RANKL and its receptor RANK in the lungs of mice exposed to long-term CS exposure. Next, we studied RANKL and RANK expression under CS extract (CSE) stimulation in vitro. Lastly, we studied the in vitro biological function of RANKL in CS-induced production of MMP-9. Results: Both RANKL and RANK were highly expressed in AMs in CS-exposed mice, but not in the control mice. In vitro, CSE increased the expressions of RANKL and RANK in macrophages. AMs responded to CSE and RANKL stimulation by overexpressing MMP-9, and CSE-induced MMP-9 expression was partly blocked by using monoclonal anti-RANKL antibody. Conclusion: RANKL/RANK pathway mediates CS-induced MMP-9 expression in AMs, suggesting a novel mechanism for CS-associated emphysema. Keywords: COPD, receptor activator of nuclear factor-κB ligand, RANK, alveolar macrophages, MMP-9

Qi Li,1 Fen Chen,2 Yun Liu,1 Shihui Yu,1 Xiumei Gai,1 Mingzhu Ye,1 Xinggang Yang,1 Weisan Pan1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110016, People’s Republic of China Background: The objective of this study was to develop a more bio-available and safe nanosuspension of meloxicam (MX), which could dramatically improve inflammation targeting. Methods and results: MX-loaded bovine serum albumin (BSA) nanosuspensions were prepared using acid–base neutralization in aqueous solution and the prepared nanosuspensions were characterized. The results obtained showed that the prepared nanosuspensions had a narrow size distribution with a mean particle size of 78.67±0.22 nm, a polydispersity index of 0.133±0.01, and a zeta potential of -11.87±0.91 mV. The prepared MX nanosuspensions were spherically wrapped by BSA with a smooth surface as shown by transmission electron microscopy. Stability studies showed that the nanosuspensions were physically stable at 4°C with a shelf life of at least 6 months. In the in vitro dissolution test, the MX-loaded BSA nanosuspension (MX-BSA-NS) exhibited sustained release. In addition, an in vivo pharmacokinetic study in rats following intravenous injection showed that the half-life (t1/2), mean residence time (MRT), and area under the concentration–time curve (AUC0–∞) of MX-BSA-NS was increased by 169.83%, 150.13%, and 148.80%, respectively, in comparison with MX conventional solution (MX solution). Furthermore, results from inflammation targeting studies showed that the concentration of MX increased significantly in inflamed tissues but was reduced in normal tissues compared with the MX solution group after injection of MX-BSA-NS. Conclusion: The prepared MX-BSA-NS significantly increased the inflammation-targeting properties and bioavailability of MX, suggesting its potential as a promising formulation for the targeted drug delivery of MX in future clinical applications. Keywords: nanosuspensions, inflammation targeting, BSA, meloxicam, acid–base neutralization

Yan Di,1 Ting Li,1 Zhihong Zhu,1 Fen Chen,2 Lianqun Jia,2 Wenbing Liu,3 Xiumei Gai,1 Yingying Wang,1 Weisan Pan,1 Xinggang Yang1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 2Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 3Key Laboratory of Structure-Based Drug Design & Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang, China Abstract: The aim of this study was to simultaneously introduce pH sensitivity and folic acid (FA) targeting into a micelle system to achieve quick drug release and to enhance its accumulation in tumor cells. Paclitaxel-(+)-α-tocopherol (PTX-VE)-loaded mixed micelles (PHIS/FA/PM) fabricated by poly(ethylene glycol) methyl ether-poly(histidine) (MPEG-PHIS) and folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) were characterized by dynamic light scattering and transmission electron microscopy (TEM). The mixed micelles had a spherical morphology with an average diameter of 137.0±6.70 nm and a zeta potential of -48.7±4.25 mV. The drug encapsulation and loading efficiencies were 91.06%±2.45% and 5.28%±0.30%, respectively. The pH sensitivity was confirmed by changes in particle size, critical micelle concentration, and transmittance as a function of pH. MTT assay showed that PHIS/FA/PM had higher cytotoxicity at pH 6.0 than at pH 7.4, and lower cytotoxicity in the presence of free FA. Confocal laser scanning microscope images demonstrated a time-dependent and FA-inhibited cellular uptake. In vivo imaging confirmed that the mixed micelles targeted accumulation at tumor sites and the tumor inhibition rate was 85.97%. The results proved that the mixed micelle system fabricated by MPEG-PHIS and FA-PEG-VE is a promising approach to improve antitumor efficacy. Keywords: pH sensitive, folic acid targeting, mixed micelles, drug delivery, in vivo antitumor activity

Geologic reservoirs containing gas hydrate occur beneath permafrost environments and within marine continental slope sediments, representing a potentially vast natural gas source. Numerical simulators provide scientists and engineers with tools for understanding how production efficiency depends on the numerous, interdependent (coupled) processes associated with potential production strategies for these gas hydrate reservoirs. Confidence in the modeling and forecasting abilities of these gas hydrate reservoir simulators (GHRSs) grows with successful comparisons against laboratory and field test results, but such results are rare, particularly in natural settings. The hydrate community recognized another approach to building confidence in the GHRS: comparing simulation results between independently developed and executed computer codes on structured problems specifically tailored to the interdependent processes relevant for gas hydrate-bearing systems. The United States Department of Energy, National Energy Technology Laboratory, (DOE/NETL), sponsored the first international gas hydrate code comparison study, IGHCCS1, in the early 2000s. IGHCCS1 focused on coupled thermal and hydrologic processes associated with producing gas hydrates from geologic reservoirs via depressurization and thermal stimulation. Subsequently, GHRSs have advanced to model more complex production technologies and incorporate geomechanical processes into the existing framework of coupled thermal and hydrologic modeling. This paper contributes to the validation of these recent GHRS developments by providing results from a second GHRS code comparison study, IGHCCS2, also sponsored by DOE/NETL. IGHCCS2 includes participants from an international collection of universities, research institutes, industry, national laboratories, and national geologic surveys. Study participants developed a series of five benchmark problems principally involving gas hydrate processes with geomechanical components. The five problems range from simple geometries with analytical solutions to a representation of the world's first offshore production test of methane hydrates, which was conducted with the depressurization method off the coast of Japan. To identify strengths and limitations in the various GHRSs, study participants submitted solutions for the benchmark problems and discussed differing results via teleconferences. The GHRSs evolved over the course of IGHCCS2 as researchers modified their simulators to reflect new insights, lessons learned, and suggested performance enhancements. The five benchmark problems, final sample solutions, and lessons learned that are presented here document the study outcomes and serve as a reference guide for developing and testing gas hydrate reservoir simulators.

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10-3, two-tailed Fisher's exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10-2, two-tailed Fisher's exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10-4, two-tailed Fisher's exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS.

ECH was observed to inhibit [Ca2+]cyt increase in NE-induced PASMCs in a concentration-dependent manner, effectively reducing abnormal cell proliferation. It also reduced the expression of Transient receptor potential channel (TRPC) 1 (TRPC1), TRPC4, TRPC6, and calmodulin in PASMCs. In vivo studies demonstrated that ECH lowered the expression of these proteins in lung tissues of HPH rats, significantly decreased mean pulmonary artery pressure, and mitigated PVR.

Abstract Quality teacher–child interaction is considered one of the primary mechanisms through which educational experience fosters the development of children’s competencies. Teachers’ self-efficacy and beliefs about developmentally appropriate practices influence the quality of classroom interaction. However, the findings are mixed, and more research must be done within the preschool teacher population. The present study investigated teacher-related factors influencing teacher–child interaction quality with preschool children. Two rating scales and one observation measure were used to survey and observe 55 preschool teachers in preschool centres of Arba Minch town, Ethiopia. Statistically significant positive correlations were found between teacher factors (i.e., teacher belief, self-efficacy, teaching experience) and teacher–child interaction quality (emotional support, classroom organization, and instructional support). Teacher belief significantly predicted teachers’ emotional support and classroom organization, while teaching experience significantly predicted instructional support. The findings of this study have implications for concerned bodies striving to achieve the 2030 sustainable development goals aimed at increasing the supply of qualified teachers to ensure all girls and boys have access to quality early childhood development and care so that they are ready for primary education, especially in the least developed countries.

The new energy is connected to the distribution network in the form of distributed generation, which brings uncontrollability, randomness and volatility to the system. With the help of modern power electronics, information and communication and automatic control technologies, the active distribution network with flexibility and controllability has become a development trend. The active distribution network planning is one of the major research fields in recent years. Based on the research results in this field at home and abroad, the research contents and methods of active distribution network planning were summarized, analyzed and prospected. The basic structure of the active distribution network was described, and the characteristics of the components of the distribution network were introduced. According to the different control variables, the planning models of active distribution network were classified, the optimization objectives in the model were summarized. The commonly used model solving algorithms and their advantages and disadvantages were analyzed and summarized. Through the discussion of key issues, the development trend of active distribution network in the future was analyzed.

We investigated correlated photon-pair generation via spontaneous four-wave mixing in an integrated chalcogenide Ge11.5As24Se64.5 photonic nanowire. The coincidence to accidental ratio, a key measurement for the quality of correlated photon-pair sources, was measured to be only 0.4 when the photon pairs were generated at 1.9 THz detuning from the pump frequency due to high spontaneous Raman noise in this regime. However, the existence of a characteristic low-Raman window at around 5.1 THz in this material's Raman spectrum and dispersion engineering of the nanowire allowed us to generate photon pairs with a coincidence to accidental ratio of 4.5, more than 10 times higher than the 1.9 THz case. Through comparing the results with those achieved in chalcogenide As2S3 waveguides which also exhibit a low Raman-window but at a larger detuning of 7.4 THz, we find that the position of the characteristic low-Raman window plays an important role on reducing spontaneous Raman noise because the phonon population is higher at smaller detuning. Therefore the ultimate solution for Raman noise reduction in Ge11.5As24Se64.5 is to generate photon pairs outside the Raman gain band at more than 10 THz detuning. [ABSTRACT FROM AUTHOR]