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Min Gao,1,2,* Wenhua Sang,1,3,4,* Kun Mi,1,3,4 Jiancong Liu,1,3,4 Yudong Liu,1,3,4 Wenge Zhen,1,3,4 Bang An2 1Department of Affective Disorders II, Hebei Provincial Mental Health Center, Baoding, People’s Republic of China; 2Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, People’s Republic of China; 4The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhua Sang, Department of Affective Disorders II, Hebei Provincial Mental Health Center, Hebei Key Laboratory of Major Mental and Behavioral Disorders, The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China, Email whsang997169@163.com Bang An, Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China, Email xyanbang@163.comObjective: Only about one-third of depressed patients respond to initial antidepressant treatment. Therefore, it is crucial to find effective predictors of antidepressants. The purpose of our study was to learn the relationship between EEG theta power, theta asymmetry, and the efficacy of escitalopram.Methods: The study included 34 patients with depression. Before and after each patient’s course of treatment, EEG data was gathered. Both the Hamilton Anxiety Scale (HAMA) and the 17-item Hamilton Depression Scale (HAMD-17) were evaluated simultaneously. The natural logarithm of right frontal theta power minus left frontal theta power was used to calculate inter-electrode theta asymmetry (AT).Results: First, our study found no statistically significant difference between intra-electrode theta power and inter-electrode AT before and after treatment (P ≥ 0.05). When we later looked at the data regarding treatment effects, the findings revealed that patients (n = 9) who did not respond to treatment had lower baseline theta power at C4 [6.190 (2.000, 12.990) vs 15.800 (7.255, 22.330), z = − 2.166, P = 0.030]. The two groups had no difference in other electrodes (P ≥ 0.05). The AT of C3/C4 in non-responders (n = 9) was lower [0.012 (0.795) vs 0.733 (0.539), t = − 3.224, P = 0.005]. However, there was no difference in inter-electrode AT between the two groups in F3/F4 and F7/F8 (P ≥ 0.05). We finally show that the theta power at C4 was negatively correlated with HAMD scores before treatment (r = − 0.346, P = 0.045).Conclusion: Our findings determined that increased theta power and positive asymmetry in the right frontal-central area correlate with favourable escitalopram treatment, providing a basis for finding predictive markers for antidepressants.Keywords: depression, EEG, theta power, theta asymmetry, treatment effect

Wanyue Sang,1,2,* Lu Wang,1,2,* Xiaoji Yan,3,* Huaxin Sun,1,2 Yafan Han,1,2 Feifei Wang,1,2 Baopeng Tang,1,2 Yaodong Li1,2 1Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Emergency, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaodong Li; Baopeng Tang, Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang, 830000, People’s Republic of China, Tel/Fax +86 15099538881 ; +86 9914362614, Email lyd123@xjmu.edu.cn; tangbaopeng1111@163.comObjective: Atrial fibrillation (AF) is a common tachyarrhythmia whose pathogenesis remains elusive. In the present study, we aimed to investigate the pathological mechanism of mitophagy and immunoinfiltration in AF.Methods: First, we identified differentially expressed mitophagy-related genes (DEMRGs) based on the GSE79768 and GSE115574 datasets, subjecting them to functional enrichment analysis. STRING, TRRUST, miRNet, miRwalk, and Cytoscape were used to explore the potential regulatory roles of downstream signaling pathways. Subsequently, the random forest method was used to construct the AF risk model, and the DEMRGs most correlated with AF risk were determined by combining the Gini index. ssGSEA algorithm, NMF algorithm, and unsupervised clustering were used to subdivide AF molecular types. We then studied the characteristics of mitophagy- and immune infiltration-related genes in AF. Ultimately, we detected the expression of key genes in canine atrial tissues and HL-1 cells by immunofluorescence and Western blot.Results: Mitophagy and immune infiltration were significantly enriched and activated in AF samples. Thirty-seven DEMRGs were screened, of which MAPK1, VDAC1, MAPK14, and MTERF3 were most associated with AF risk. The risk model based on these could identify patients at a high risk of AF. The infiltration of immunocells such as mast cells and neutrophils was significantly different among AF types. Finally, expression verification indicated that the expression trend of four key genes in canine atrial muscle tissue and HL-1 cells was consistent.Conclusion: We found that mitophagy may participate in AF progression through immune activation. In addition, the AF risk prediction model composed of VDAC1, MAPK1, MAPK14, and MTERF3 has a good AF prediction performance, which provides new ideas for the study of AF pathogenesis and potential therapeutic targets.Keywords: atrial fibrillation, mitophagy, molecular subtypes, immune infiltration, random forest

Nanovesicles produced with lipids and polymers are promising devices for drug and bioactive delivery and are of great interest in pharmaceutical applications. These nanovesicles can be engineered for improvement in bioavailability, patient compliance or to provide modified release or enhanced delivery. However, their applicability strongly depends on the safety and low immunogenicity of the components. Despite this, the use of unsaturated lipids in nanovesicles, which degrade following oxidation processes during storage and especially during the proper routes of administration in the human body, may yield toxic degradation products. In this study, we used a biopolymer (chitosan) labeled with flavonoid (catechin) as a component over a lipid bilayer for micro- and nanovesicles and characterized the structure of these vesicles in oxidation media. The purpose of this was to evaluate the in situ effect of the antioxidant in three different vesicular systems of medium, low and high membrane curvature. Liposomes and giant vesicles were produced with the phospholipids DOPC and POPC, and crystalline cubic phase with monoolein/DOPC. Concentrations of chitosan–catechin (CHCa) were included in all the vesicles and they were challenged in oxidant media. The cytotoxicity analysis using the MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) revealed that concentrations of CHCa below 6.67 µM are non-toxic to HeLa cells. The size and zeta potential of the liposomes evidenced the degradation of their structures, which was minimized by CHCa. Similarly, the membrane of the giant vesicle, which rapidly deteriorated in oxidative solution, was protected in the presence of CHCa. The production of a lipid/CHCa composite cubic phase revealed a specific cubic topology in small-angle X-ray scattering, which was preserved in strong oxidative media. This study demonstrates the specific physicochemical characteristics introduced in the vesicular systems related to the antioxidant CHCa biopolymer, representing a platform for the improvement of composite nanovesicle applicability.

Abstract To gain insight into sialic acid biology and sialidase/neuraminidase (NEU) expression in mature human neutrophil (PMN)s, we studied NEU activity and expression in PMNs and the HL60 promyelocytic leukemic cell line, and changes that might occur in PMNs undergoing apoptosis and HL60 cells during their differentiation into PMN-like cells. Mature human PMNs contained NEU activity and expressed NEU2, but not NEU1, the NEU1 chaperone, protective protein/cathepsin A(PPCA), NEU3, and NEU4 proteins. In proapoptotic PMNs, NEU2 protein expression increased > 30.0-fold. Granulocyte colony-stimulating factor protected against NEU2 protein upregulation, PMN surface desialylation and apoptosis. In response to 3 distinct differentiating agents, dimethylformamide, dimethylsulfoxide, and retinoic acid, total NEU activity in differentiated HL60 (dHL60) cells was dramatically reduced compared to that of nondifferentiated cells. With differentiation, NEU1 protein levels decreased > 85%, PPCA and NEU2 proteins increased > 12.0-fold, and 3.0-fold, respectively, NEU3 remained unchanged, and NEU4 increased 1.7-fold by day 3, and then returned to baseline. In dHL60 cells, lectin blotting revealed decreased α2,3-linked and increased α2,6-linked sialylation. dHL60 cells displayed increased adhesion to and migration across human bone marrow-derived endothelium and increased bacterial phagocytosis. Therefore, myeloid apoptosis and differentiation provoke changes in NEU catalytic activity and protein expression, surface sialylation, and functional responsiveness.

Bo Pu,1,2,* Wenyuan Sang,2 Juan Yang,3,* Siyu Ji,2 Zhiwei Tang1 1School of Public Affairs and Administration, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2School of Business and Tourism, Sichuan Agricultural University, Chengdu, 611830, People’s Republic of China; 3School of Economics and Management, Southwest Jiaotong University, Chengdu, 610031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Pu; Wenyuan Sang Email ppuubo@hotmail.com; lynnnnyy@163.comBackground: This study explores the causal relationship between entrepreneurial leadership and employees’ tacit knowledge sharing in start-ups. Construct a moderated mediation model to test the mediating role of affective commitment and the moderating role of career growth opportunities.Methods: A questionnaire was used to collect data, and 485 samples of employees in Chinese start-ups were collected. Regression analysis and structural equation model were used to analyze data and verify hypotheses.Results: The study shows that entrepreneurial leadership has a significant positive effect on employees’ affective commitment and tacit knowledge sharing. Affective commitment plays a mediating effect between entrepreneurial leadership and employees’ tacit knowledge sharing. Career growth opportunities play a positive moderating role in the impact of entrepreneurial leadership on affective commitment and tacit knowledge sharing, and positively moderate the indirect effect of entrepreneurial leadership on tacit knowledge sharing through affective commitment.Conclusion: The research illustrates that the managers of start-ups can improve employees’ affective commitment by giving full play to entrepreneurial leadership and combining the career growth opportunities provided by the organization. Employees’ tacit knowledge sharing behavior is stimulated, providing guiding value for knowledge management and the human resource management of start-ups.Keywords: entrepreneurial leadership, tacit knowledge sharing, affective commitment, career growth opportunities

Abstract We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.

Ziyuan Shen,1,&ast; Fei Wang,2,&ast; Chenlu He,1,&ast; Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM).Methods: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival.Results: The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cut-off point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan–Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (< 2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis.Discussion: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.Keywords: diffuse large B-cell lymphoma, prognostic nutrition index, propensity score matched, prognosis

Background: Outcomes in rectal cancer are dependent on tumor height. Modalities for assessing tumor height include MRI, endoscopy, and digital rectal exam (DRE). We seek to identify correlations between these modalities. Methods: Retrospective analysis of 120 rectal cancer patients at a single institution. Correlation coefficients and distance of the tumor to anal verge between MRI, endoscopy, and DRE were compared by region. Results: The distances of tumor (cm) from anal verge were: MRI: 6.2 ± 3.0, endoscopy: 5.9 ± 2.9, DRE: 5.4 ± 2.4 (p = 0.238). Endoscopy and DRE strongly correlated with MRI (spearman coefficient 0.899 and 0.842, respectively). Endoscopy and DRE also strongly correlated (spearman coefficient 0.876). Correlation coefficients were highest in the middle rectum, weak in the low rectum, and non-correlated in the upper rectum. Conclusions: MRI, endoscopy, and DRE strongly correlated overall. DRE demonstrated the lowest average distance. Correlations differed by region, suggesting high or low rectal tumors are difficult to characterize.

In previous work, we showed that cancer cells do not depend on glycolysis for ATP production, but they do on fatty acid oxidation. However, we found some cancer cells induced cell death after glucose deprivation along with a decrease of ATP production. We investigated the different response of glucose deprivation with two types of cancer cells including glucose insensitive cancer cells (GIC) which do not change ATP levels, and glucose sensitive cancer cells (GSC) which decrease ATP production in 24 h. Glucose deprivation-induced cell death in GSC by more than twofold after 12 h and by up to tenfold after 24 h accompanied by decreased ATP production to compare to the control (cultured in glucose). Glucose deprivation decreased the levels of metabolic intermediates of the pentose phosphate pathway (PPP) and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) in both GSC and GIC. However, glucose deprivation increased reactive oxygen species (ROS) only in GSC, suggesting that GIC have a higher tolerance for decreased NADPH than GSC. The twofold higher ratio of reduced/oxidized glutathione (GSH/GSSG) in GIS than in GSC correlates closely with the twofold lower ROS levels under glucose starvation conditions. Treatment with N-acetylcysteine (NAC) as a precursor to the biologic antioxidant glutathione restored ATP production by 70% and reversed cell death caused by glucose deprivation in GSC. The present findings suggest that glucose deprivation-induced cancer cell death is not caused by decreased ATP levels, but rather triggered by a failure of ROS regulation by the antioxidant system. Conclusion is clear that glucose deprivation-induced cell death is independent from ATP depletion-induced cell death.

Background: The root and canal morphology of maxillary first permanent molars (MFPMs) is a very widely studied issue in endodontics. However, only one study has been conducted to date on this issue using cone-beam computed tomography (CBCT) in India, and the sample consisted of extracted teeth. Aim: To investigate the root and canal morphology of MFPMs in an Indian population, by using CBCT. Methods and Material: 487 bilateral MFPMs (974 teeth) were assessed and the root and canal morphology were determined according to Vertucci's classification. In addition, the prevalence of a second mesiobuccal canal in the mesiobuccal root (MB2) was correlated with gender, age and arch side. Results: Three roots were most commonly found in the MFPMs regardless of gender (P > 0.05), but this prevalence varied according to the side of the dental arch (P < 0.05). MB2 was present in 77.5% of 3-rooted teeth. Patients above 60 years had a higher incidence of these canals (84.7%) (P < .05). The occurrence of bilateral MB2 was 71.8% in 3-rooted MFPMs. Gender had no significant impact on the occurrence of bilateral MB2 in 3-rooted MFPMs (P > .05). The most common canal configuration was type IV (46.5%) and I (98.9%) in the mesiobuccal and distobuccal roots, respectively (P < .05). The prevalence of MB2 in 3-rooted MFPMs was higher in patients above 60 years of age. Conclusions: The root and canal morphology of MFPMs in an Indian population may have significant variations depending on the dental arch side and patient age.

Purpose: Debate exists regarding the optimal management for patients with stage III non-small-cell lung cancer (NSCLC). Recent inclusion of chemotherapeutic data in the Surveillance, Epidemiology, and End Results (SEER) database has made it possible to identify patients with NSCLC who received chemotherapy. We hypothesized that patients with stage III NSCLC experience improved overall survival from trimodality therapy (TMT) versus definitive chemoradiation therapy (CRT) alone. Materials and Methods: We analyzed the overall survival of stage III NSCLC patients based on the receipt of TMT versus CRT alone. This included crude and adjusted univariate models as well as crude and doubly robust adjusted multivariable analyses, both utilizing propensity score matching and inverse probability of treatment weighting. Factors included in the multivariable analyses included: age, sex, marital status, income, date of diagnosis, primary site, histology, grade, T stage, N stage, and intended treatment. Planned subset analyses were performed for stage III(N2) patients. Results: Adult patients with stage III NSCLC (N = 9008) from the SEER database were included in our analyses. In our univariate analyses, an overall survival benefit was observed for TMT versus CRT (CrudeHR = 0.58, 95% CI = 0.55–0.61, p

Background:. We describe our experience with bidirectional forehead narrowing and eyebrow lifting (BiNaLi), a surgical technique we have been practicing for several years to correct facial esthetic issues of patients such as long forehead, high hairline, and low eyebrow level, which helps us achieve forehead height reduction with eyebrow lifting, using 1 incision line in a one-stage procedure. Methods:. We divided 576 patients who visited our institution between March 2014 and February 2019 into 4 groups: long forehead only (group I), low eyebrow level (groups II and IV), and M-shaped hairline (groups III and IV); BiNaLi operation was performed as appropriate for each group. Results:. The preoperative length of the median area of the forehead was 7.3 cm, and the mean postoperative change in the length of the same was 1.4 cm. The lateral forehead length was also measured for groups III and IV. The mean preoperative length was 7.7 cm, and the mean postoperative change in the length was 1.7 cm. Eyelid length was also measured for groups II and IV. The mean preoperative length was 0.7 cm, and the mean postoperative change in the length was 0.3 cm. More than 90% of the patients gave a score of 4.0 or higher for esthetic satisfaction. Conclusions:. We designed a BiNaLi technique to satisfy patients’ facial esthetic needs using changes in flap movement direction, adjustment in the range of skin excision, and differences in flap dissection. A single operation can have various effects, including achieving forehead shortening, clear double-fold line through eyebrow lifting, and correction of a mild M-shaped hairline.

Microfluidics is an emerging technology that can be employed as a powerful tool for designing lipid nano-microsized structures for biological applications. Those lipid structures can be used as carrying vehicles for a wide range of drugs and genetic materials. Microfluidic technology also allows the design of sustainable processes with less financial demand, while it can be scaled up using parallelization to increase production. From this perspective, this article reviews the recent advances in the synthesis of lipid-based nanostructures through microfluidics (liposomes, lipoplexes, lipid nanoparticles, core-shell nanoparticles, and biomimetic nanovesicles). Besides that, this review describes the recent microfluidic approaches to produce lipid micro-sized structures as giant unilamellar vesicles. New strategies are also described for the controlled release of the lipid payloads using microgels and droplet-based microfluidics. To address the importance of microfluidics for lipid-nanoparticle screening, an overview of how microfluidic systems can be used to mimic the cellular environment is also presented. Future trends and perspectives in designing novel nano and micro scales are also discussed herein.

Wei Xiong,1 Wei Sang,1 Ke Gang Linghu,1 Zhang Feng Zhong,1 Wai San Cheang,1 Juan Li,2 Yuan Jia Hu,1 Hua Yu,1,3,4 Yi Tao Wang1 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China; 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, China; 3Hong Kong Baptist University Shenzhen Research Center, Shenzhen, Guangdong, China; 4School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China Introduction: Berberine (BBR) is a plant-derived benzylisoquinoline alkaloid and has been demonstrated to be a potential treatment for various chronic diseases. The poor water solubility and P-glycoprotein (Pgp)-mediated drug efflux are the main challenges for its further application in a clinical setting. Materials and methods: In this study, a Brij-S20 (BS20)-modified nanocrystal formulation (BBR-BS20-NCs) has been developed and investigated with the purpose of improving the intestinal absorption of BBR. The physicochemical properties of the developed BBR-BS20-NCs were characterized and the enhancement of the BBR-BS20-NCs on BBR absorption were investigated both in vitro and in vivo. Results: The results indicated that BS20 could significantly enhance the intracellular uptake of BBR in MDCK-MDR1 cells via a short-term and reversible modulation on the Pgp function, accompanied by a marked increase in Pgp mRNA expression but without significant influence on the Pgp protein expression. Moreover, the morphology of the prepared BBR-BS20-NCs was observed to be prism-like, with a smooth surface and an average diameter of 148.0 ± 3.2 nm. Compared to raw BBR and physical mixture, BBR-BS20-NCs facilitated the dissolution rate and extent of release of BBR in aqueous solution, and further increased the absorption of BBR in MDCK-MDR1 monolayer by overcoming the Pgp-mediated secretory transport (Papp[BL-AP] values of 2.85 ± 0.04 × 10-6 cm/s, 2.21 ± 0.14 × 10-6 cm/s, and 2.00 ± 0.07 × 10-6 cm/s for pure BBR, physical mixture, and BBR-BS20-NCs, respectively). Significant improvements in the maximum concentration observed (Cmax) and area under drug concentration-time curve (AUC0–t) of BBR-BS20-NCs were obtained in pharmacokinetic studies compared to pure BBR, and the relative bioavailability of BBR-BS20-NCs to pure BBR was 404.1%. Conclusion: The developed BBR-BS20-NCs combine the advantages of nanocrystal formulation and functional excipient. The novel pharmaceutical design provides a new strategy to improve the oral bioavailability of those drugs with both poor water solubility and Pgp-mediated efflux. Keywords: berberine, poor water solubility, Pgp-mediated drug efflux, Brij, nanocrystals

The sonocatalytic activity of nano-sized ZnO powder was studied via the degradation of the Direct Blue 71 azo dye. The nano-sized ZnO powder that was selected was the same as that which was synthesized and characterized in our previous study. The influences of six operational parameters including the initial pH, the initial concentration, the dose of sonocatalyst, the ultrasound frequency, the ultrasound power, and the process time were investigated on the basis of process efficiency and energy consumption. The design of experiments was applied and the experiments were conducted according to the design. The experiments were carried out in a batch reactor. The experimentally obtained dye removal percent (DR%) and the energy consumption per mass ranged from 0.03–100 and 0.19–1273 (wh/g), respectively. The data were used for modelling by using reduced quadratic multiple regression models and the artificial neural network (ANN). Multi-objective optimization of DR% and EPM was applied by using the genetic algorithm (GA) over the outperformed ANN models. The mineralization was studied using total organic carbon analysis. The study indicated promising results in the application of both the novel sonocatalyst and the Artificial Intelligent Approaches.

Functionalized nanofluidics devices have recently emerged as a powerful platform for applications of energy conversion. Inspired by biological cells, we theoretically studied the effect of the interaction between the nanoparticle and the plate which formed the brush layer modified by functional zwitterionic polyelectrolyte (PE) on the bulk charge density of the nanoparticle brush layer, and the charge/discharge effect when the distance between the particle and the plate was changed. In this paper, The Poisson–Nernst–Planck equation system is used to build the theoretical model to study the interaction between the nanoparticle and the plate modified by the PE brush layer, considering brush layer charge regulation in the presence of multiple ionic species. The results show that the bulk charge density of the brush layer decreases with the decrease of the distance between the nanoparticle and the flat substrate when the interaction occurs between the nanoparticle and the plate. When the distance between the particle and the plate is about 2 nm, the charge density of the brush layer at the bottom of the particle is about 69% of that at the top, and the electric field energy density reaches the maximum value when the concentration of the background salt solution is 10 mm.

The rebound of impinging droplets is a defining characteristic of superhydrophobic surfaces; yet, such an intriguing interfacial phenomenon can be effectively suppressed by adding a tiny amount of flexible polymers to induce non-Newtonian viscoelastic properties. In this work, however, we demonstrate the promoting effects of surface heating on the rebound of impinging viscoelastic droplets on superhydrophobic surfaces. The underlying mechanism for the promotion is that the local heat transfer at the liquid–solid interface causes the fast evaporation of the liquid and thus the breakup of the formed viscoelastic filaments, which hinder droplet recoiling. Therefore, the lower threshold velocity for rebound increases while the upper threshold velocity for rebound suppression decreases with increasing surface temperature, resulting in a wider regime for droplet rebound in the impact phase diagram. The surface heating effect on liquid–solid interactions also leads to a nontrivial dependence of the contact time on the impact velocity and a linear decrease of the restitution coefficient with the Weber number for diverse bouncing viscoelastic droplets, which can be rationalized by coupling the interfacial force and energy analyses. We envision that these findings would be useful in technological processes requiring control the retention of viscoelastic liquids on solid surfaces.

Brain age estimation from anatomical features has been attracting more attention in recent years. This interest in brain age estimation is motivated by the importance of biological age prediction in health informatics, with an application to early prediction of neurocognitive disorders. It is well-known that normal brain aging follows a specific pattern, which enables researchers and practitioners to predict the age of a human's brain from its degeneration. In this paper, we model brain age predicted by cortical thickness data gathered from large cohort brain images. We collected 2,911 cognitively normal subjects (age 45–91 years) at a single medical center and acquired their brain magnetic resonance (MR) images. All images were acquired using the same scanner with the same protocol. We propose to first apply Sparse Group Lasso (SGL) for feature selection by utilizing the brain's anatomical grouping. Once the features are selected, a non-parametric non-linear regression using the Gaussian Process Regression (GPR) algorithm is applied to fit the final age prediction model. Experimental results demonstrate that the proposed method achieves the mean absolute error of 4.05 years, which is comparable with or superior to several recent methods. Our method can also be a critical tool for clinicians to differentiate patients with neurodegenerative brain disease by extracting a cortical thinning pattern associated with normal aging.

Objective: Although there is strong evidence that childhood trauma is associated with the development of depression and anxiety, relatively few studies have explored potential mediating factors for this relationship. The present study aimed to evaluate the mediating role of rumination in the link between childhood trauma and mood status such as depression, anxiety and affective lability.Materials and Methods: Two hundred and seven non-clinical participants completed the Childhood Trauma Questionnaire, the Ruminative Response Scale, the Beck Depression Inventory, the State Anxiety Inventory, and the Affective Lability Scale. Structural equation modeling was used to evaluate the results.Results: Our results supported that rumination is a meaningful mediator between childhood trauma and depression/anxiety in non-clinical participants. The mediation model indicated that childhood trauma and its subtypes are linked to depression and anxiety through three subtypes of rumination, thereby supporting a significant indirect relationship (Standardized coefficient [SC] = 0.56, p < 0.001 for the path from trauma to rumination; SC = 0.67, p < 0.001, from rumination to mood). The direct relationship between childhood trauma and mood symptoms was also significant in a model including rumination (SC = 0.68, p < 0.001). The mediation effect of rumination in the relationship between childhood trauma and mood was more predominant in female participants.Conclusions: The present study found that rumination mediates the influence of childhood trauma on the development of mood symptoms in non-clinical participants. Childhood trauma appears to be a critical determinant for developing symptoms of depression and anxiety.

Epidermal growth factor (EGF), which promotes epidermal regeneration and wound closure, is important for the proliferation and differentiation of epidermal and epithelial tissues in animals. Exogenous EGF is a promising therapeutic agent for wound healing, but its general use is restricted by the limited availability of this protein. In this work, we show that the transfection of mouse BALB/MK keratinocytes, which are totally dependent on EGF for growth and migration, with mature cDNA for human EGF via a retroviral vector abolished the cells requirement for exogenous EGF. The transformed cells had normal morphology and a growth rate that varied according to the source of the retroviral vector used. Keratinocyte transfection with EGF cDNA provides a time- and cost-efficient means of culturing keratinocytes and yields cells that may be useful for skin grafting.

Depletion of alloreactive T-lymphocytes from allogeneic bone marrow tansplants may prevent graft-versus-host disease (GVHD) without impairing donor cell engraftment, immunity, and the graft-versus-leukemia (GVL) effect. Alloreactive T-cells may be identified by their expression, upon activation, of CD137, a costimulatory receptor and putative surrogate marker for antigen-specific effector T-cells. In this context, we tested the use of anti-CD137-saporin immunotoxin to selectively deplete mouse and human alloreactive T-cells. Anti-CD137 antibodies were internalized by cells within 4 h of binding to the cell surface CD137, and anti-CD137-saporin immunotoxin effectively killed polyclonally activated T-cells or antigen-stimulated T-cells. Transfer of donor T-cells after allodepletion with anti-CD137-saporin immunotoxin failed to induce any evident expression of GVHD; however, a significant GVL effect was observed. Targeting of CD137 with an immunotoxin was also effective in killing polyclonally activated or alloreactive human T-cells. Our results indicate that anti-CD137-saporin immunotoxin may be used to deplete alloreactive T-cells prior to bone marrow transplantation and thereby prevent GVHD and the relapse of leukemia.

PURPOSE: To compare the accuracy of estimating prostatic volume with digital rectal examination (DRE) by urological staffs with different experiences. Measurement of prostatic volume with transrectal ultrasonography (TRUS) serves as the reference standard. MATERIALS AND METHODS: Thirty-nine consecutive male patients admitted with acute urinary retention had their prostatic volume estimated with DRE by a urology junior trainee, a urology higher trainee and a trained urologist. All patients had TRUS to measure their prostatic volumes. Pearson correlation coefficients (r) were used to assess the relationships between the prostatic volume measured with TRUS and that estimated with DRE by the 3 urological staffs. Wilcoxon signed ranks tests were used to compare the discrepancies between the prostatic volume measured with TRUS and that estimated with DRE for the 3 Urological staffs, and to assess the inter-observer differences of these discrepancies. RESULTS: The correlation coefficients for the 3 urological staffs were r = 0.573 for the urology junior trainee, r = 0.541 for the urology higher trainee, and r = 0.640 for the trained urologist. The median discrepancies between the prostatic volume measured with TRUS and that estimated with DRE were -9.1 mL for the urology junior trainee, -1.3 mL for the urology higher trainee and 0.9 mL for the trained urologist. These discrepancies were statistically significant only in the case of urology junior trainee (p = 0.015, Wilcoxon signed ranks test). The difference in these discrepancies was statistically significant only between the urology junior trainee and the trained urologist (p = 0.003, Wilcoxon signed ranks test). CONCLUSIONS: The trained urologist was more accurate in estimating prostatic volume with DRE than the urology junior trainee.

4-1BB (CD137, TNFRSF9), a member of the activation-induced tumor necrosis factor receptor family, is a powerful T-cell costimulatory molecule. It generally enhances CD8(+) T responses and even breaks the tolerance of CD8(+) T cells in an antigen-specific manner. In the present study we found that it was expressed in the placentas of pregnant mice and that its expression coincided with that of the immunesuppressive enzyme indoleamine 2,3-dioxygenase (IDO). Therefore, we investigated whether 4-1BB signaling is involved in fetal rejection using agonistic anti-4-1BB mAb and 4-1BB-deficient mice. Treatment with agonistic anti-4-1BB mAb markedly increased the rate of rejection of allogeneic but not syngeneic fetuses, and this was primarily dependent on CD8(+) T cells. Complement component 3 (C3) seemed to be the effector molecule because 4-1BB triggering resulting in accumulation of C3 in the placenta, and this accumulation was also reversed by anti-CD8 mAb treatment. These findings demonstrate that 4-1BB triggering breaks the tolerance of CD8(+) T cells to alloantigens in the placenta. Moreover, triggering 4-1BB protected the pregnant mice from Listeria monocytogenes (LM) infection, but led to rejection of semi-allogeneic fetuses. Therefore, given the cross-recognition of alloantigen by pathogen-reactive CD8(+) T cells, the true function of 4-1BB may be to reverse the hypo-responsiveness of pathogen-reactive CD8(+) T cells in the placenta in cases of infection, even if that risks losing the fetus.

Objectives. This paper aims to analyze the feasibility and safety of single-incision laparoscopic colectomy (SILC) and its potential benefits. Methods. Systematic review was performed for the years 1983–August 2011 to retrieve all relevant literature. A total of 21 studies with 477 patients undergoing SILC were selected. Results. Range of operative times and estimated blood losses were 75–229 min and 0–100 mL, respectively. Overall conversion rate was 5.9% (28/477) and an additional laparoscopic port was used in 4.9% (16/329) cases. Range of lymph node number for malignant cases was 12–24.6 and surgical margins were all negative. Overall mortality and morbidity rate was 0.4% (2/477) and 11.7% (43/368), respectively. The length of hospital stay (LOS) varied across reports (2.7–9.2 days). Among 6 case-matched studies, one showed less blood loss in SILC as compared to LAC and 2 showed shorter LOS after SILC versus HALC or LAC/HALC groups. In addition, one study reported maximum pain score on postoperative days 1 and 2 was lower in SILS compared to LAC and HALC. Conclusions. SILC procedure is feasible and safe when performed by surgeons highly skilled in laparoscopy. In spite of technical difficulties, there may be potential benefits associated with SILC over LAC/HALC.

Vascular smooth muscle cells (VSMC) are ideal for systemic gene therapy because of their proximity to blood vessels and they have demonstrated long-term exogenous gene expression in vivo. However, the procedure generally followed to seed the transduced VSMC onto arteries denuded of endothelial cells usually induces stenosis and thrombosis, with a consequent high risk for use in humans. We demonstrate here that the vascular adventitia is a suitable place to introduce transduced VSMC and to secrete therapeutic proteins into the blood stream by a simple procedure, avoiding postoperative vascular complications. Transduced VSMC, with the retroviral vectors carrying the human growth hormone gene (hGH), were seeded into the adventitia of the rat abdominal aorta by single injection of a cell suspension. Based on the hGH and anti-hGH production in serum and on histological analysis of the removed aortas, we demonstrated hGH production over the 2-month experimental period. None of the animals used in the experiment showed stenosis, thrombosis, or other vascular or visible physiological abnormalities.

Questions: All else being equal, populations of dioecious species with a 50:50 sex ratio have only half the effective reproductive population size of bisexual species of equal abundance. Consequently, there is a need to explain how dioecious and bisexual species coexist. Increased mean individual seed mass, fecundity, and population density have all been proposed as attributes of unisexual individuals or populations that may contribute to the persistence or resilience of dioecious species. To date, no studies have compared sympatric dioecious and cosexual species with respect to all three components of fitness. In this study, we sought evidence for these compensatory advantages (higher seed mass, greater seed production per unit basal area, and higher population density) in dioecious species. Location: Five 20–25 ha forest dynamic plots spanning a latitudinal gradient in China, including two temperate, two subtropical, and one tropical forest. Methods: We used a phylogenetically corrected generalized linear modelling approach to assess the phylogenetic dependence and joint evolution of sexual system, seed mass and production, and ecological abundances among 48–333 species and 32,568–136,237 individuals per forest. Results: Across all five forests, we detected no consistent advantage for dioecious relative to sympatric cosexual species with respect to mean individual seed mass, seed production or the density of stems in any size class. Conclusions: Our study suggests that seed traits may provide compensatory mechanisms in some forests, but most often the coexistence of sexual systems cannot be explained by advantages of dioecy related to seed quality and demographic parameters. Future investigations of the factors that promote coexistence may increase our understanding by expanding the search to include attributes such as lifespan and tolerance or resistance to herbivores.