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Copper (Cu) homeostasis is attributed to a fine interplay among intake, transport, and clearance of the micronutrient in the governance of physiological processes. Cuproptosis, or Cu-induced cell death, develops as a result of intracellular Cu accumulation, and is dependent on mitochondrial respiration and tricarboxylic acid cycle to evoke protein lipidation, membrane permeabilization, cellular disruption, and cell death. Serum Cu level, which is often prognostic for disease prevalence, is closely associated with cardiometabolic risk factors, such as atherosclerosis, coronary heart disease, ischemic heart disease, heart failure, type 2 diabetes mellitus, and obesity. Preclinical evidence demonstrates that modulation of Cu intake, transport, and clearance can be harnessed for therapeutic purpose in cardiovascular and metabolic diseases. Copper (Cu) homeostasis is gaining increasing attention in human health as both Cu overload and deficiency evokes pathological changes including cardiovascular diseases (CVDs). Cu supplementation, nanocarriers, and chelators have all exhibited therapeutic promise in some human diseases, although how Cu dyshomeostasis and cuproptosis, a novel form of regulated cell death, contribute to CVD pathology remains elusive. Here, we discuss Cu dyshomeostasis and the potential role of cuproptosis in various CVDs. We evaluate underlying cellular mechanisms, aiming to provide some insights regarding the utility of targeting Cu dyshomeostasis and cuproptosis as a novel strategy in the management of CVDs. [ABSTRACT FROM AUTHOR]

Learning engagement is a crucial predictor of academic achievement. It is essential to understand the factors influencing learning engagement among nursing students, especially from the learner's perspective, which is notably scarce but vital for designing effective educational interventions. This study aims to investigate the mediating effect of self-efficacy on the relationship between professional identity and learning engagement for nursing students in higher vocational colleges. A cross-sectional electronic survey was conducted. The study was conducted in four higher vocational colleges located in Guangdong Province, China. A total of 944 first- and second-year nursing students participated in the study between October and November 2022. Data were collected with questionnaires on general information, professional identity, self-efficacy, and learning engagement and analyzed with SPSS 26.0 and PROCESS v4.1 (Model 4), exploring relationships among professional identity, self-efficacy, and learning engagement through Pearson correlations, multivariate regression, and mediation analysis with 5000 bootstrap samples. The participants exhibited moderate levels of professional identity (85.37 ± 13.52), self-efficacy (25.58 ± 5.74), and learning engagement (71.26 ± 16.17), which were all significantly correlated with each other (P < 0.01). In the model of the mediating effect, professional identity directly (β = 0.811, t = 27.484, P < 0.001) and indirectly [β = 0.112,95%CI (0.074–0.154)] significantly predicts college students' learning engagement; professional identity has a significant positive predictive effect on self-efficacy (β = 0.182, t = 14.459, P < 0.001) and self-efficacy significantly predicts learning engagement (β = 0.614, t = 8.292, P < 0.001). Furthermore, the direct effect of professional identity on learning engagement (0.699) and its mediating effect (0.112) account for 86.19 % and 13.81 % of the total effect (0.811), respectively. Participants exhibited moderate levels of professional identity, self-efficacy, and learning engagement. Professional identity and self-efficacy are interconnected and positively correlated, influencing learning engagement among nursing students, which highlights the need to foster these qualities to enhance education and future practice. • This study unveils the pivotal role of self-efficacy in mediating the impact of professional identity on the learning engagement of college nursing students for the first time. • Results reveal that nursing students demonstrated intermediate levels of professional identity, self-efficacy, and learning engagement. • Results reveal a significant positive correlation between professional identity, self-efficacy, and learning engagement. • This finding offers a new perspective for theoretical development and practical application to enhance the learning engagement of college nursing students. • The findings establish a foundational basis for the development of innovative strategies aimed at addressing the issue of diminished learning engagement among Chinese college nursing students. [ABSTRACT FROM AUTHOR]

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight. [Display omitted] • Human A549 cells expressing UCP1 perform uncoupled respiration • KSP in the alginate-gelatin induces immunosuppression and ECM production • A549-UCP1 cells and the matrix form an energy-dissipating hybrid tissue • EDHT reduces fat and relieves obesity-associated pathological conditions Wang et al. show the construction of an energy-dissipating hybrid tissue (EDHT) in vivo. EDHT demonstrates high efficacy in managing body weight and safety in mice, representing another strategy for potential anti-obesity therapy. [ABSTRACT FROM AUTHOR]

• Three pigeons performed social cooperation tasks by using neural feedback training. • They can achieve cross-brain neural synchronization after training. • The intra- and inter-brain functional connectivity enhance with the training time. • This phenomenon is related to the promotion of social cooperation among pigeons. Multi-brain network, also known as social cooperative network, is formed by multiple animal or human brains, whose changes of functional connectivity in the intra- and inter-brain during construction are unclear at present. To investigate the intra- and inter-brain functional connectivity of pigeons while performing a social cooperation task, we designed an inter-brain synchronization task to train three pigeons to synchronize their neural activities using cross-brain neurofeedback. Then the neural signals of three pigeons were simultaneously recorded by using a hyperscanning approach, and inter-brain synchronization was calculated using the phase-locked value (PLV) online. Finally, the intra- and inter-brain functional connectivity of three pigeons were analyzed. We found that during long-term neurofeedback training, with the increase of the inter-brain synchronization of three pigeons, the intra- and inter-brain functional connectivity also enhance significantly. Moreover, we also found that the above phenomenon relies on the external visual cue. These results suggest that the promotion of social cooperation is the result of the modulation between the intra- and inter-brain, which may be an underlying neural mechanism of the communication and cooperation among individuals in social networks. [ABSTRACT FROM AUTHOR]

Steroidal saponins, one of the most diverse groups of plant-derived natural products, elicit biological and pharmacological activities; however, the genes involved in their biosynthesis and the corresponding biosynthetic pathway in monocotyledon plants remain unclear. This study aimed to identify genes involved in the biosynthesis of steroidal saponins by performing a comparative analysis among transcriptomes of Paris polyphylla var. chinensis (PPC), Ypsilandra thibetica (YT), and Polygonatum kingianum (PK). De novo transcriptome assemblies generated 57,537, 140,420, and 151,773 unigenes from PPC, YT, and PK, respectively, of which 56.54, 47.81, and 44.30% were successfully annotated, respectively. Among the transcriptomes for PPC, YT, and PK, we identified 194, 169, and 131; 17, 14, and 26; and, 80, 122, and 113 unigenes corresponding to terpenoid backbone biosynthesis; sesquiterpenoid and triterpenoid biosynthesis; and, steroid biosynthesis pathways, respectively. These genes are putatively involved in the biosynthesis of cholesterol that is the primary precursor of steroidal saponins. Phylogenetic analyses indicated that lanosterol synthase may be exclusive to dicotyledon plant species, and the cytochrome P450 unigenes were closely related to clusters CYP90B1 and CYP734A1, which are UDP-glycosyltransferases unigenes homologous with the UGT73 family. Thus, unigenes of β-glucosidase may be candidate genes for catalysis of later period modifications of the steroidal saponin skeleton. Our data provide evidence to support the hypothesis that monocotyledons biosynthesize steroidal saponins from cholesterol via the cycloartenol pathway. Unlabelled Image [ABSTRACT FROM AUTHOR]

Background: Previous findings on the association between serum 25(OH)D level and stroke have been controversial. We aimed to examine whether these controversial findings could be possibly due to difference in study participant characteristics, especially age and gender differences in these studies, by analyzing the data from a representative sample of the general US population.Methods: Data of 13,642 adults 20 years or older who participated in the 2001-2006 National Health and Nutrition Examination Survey were analyzed in this study. Serum 25(OH)D was used to reflect vitamin D status. Stroke history was self-reported using questionnaires. Unadjusted and adjusted logistic regression models were fitted using SAS survey procedures to investigate the associations between 25(OH)D level and stroke for the pooled sample and age-gender subgroups (men versus women, <50 years old versus ≥50 years old), respectively.Results: After adjusting for demographic and lifestyle covariates, vitamin D deficiency (defined as serum 25(OH)D < 12 ng/mL) was significantly associated with increased risk of stroke (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.11, 2.36), and higher vitamin D levels were significantly associated with reduced risk of stroke (adjusted OR = .70, 95% CI = .51, .96). The association between high levels of serum 25(OH)D and stroke was particularly evident among young females (age ≤20 years to <50 years) (adjusted OR = .26, 95% CI = .14, .49).Conclusions: The findings add to the evidence suggesting maintaining ideal 25(OH)D levels may reduce the risk of stroke among US adults, particularly in adult women younger than 50 years. [ABSTRACT FROM AUTHOR]

Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potential mechanisms of protective effects of rutin against cardiomyocyte death. We analyzed cardiac tissues at the time point of 8 weeks after doxorubicin treatment. The results by echocardiography, TUNEL staining, Masson's trichrome staining as well as Western blot analysis revealed that doxorubicin induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were alleviated by rutin treatment. Western blot analysis indicated that the underlying mechanisms included inhibition excessive autophagy and apoptosis mediated by Akt activation. Collectively, our findings suggest that suppression of autophagy and apoptosis by administration of rutin could attenuate doxorubicin-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating this devastating side effect induced by doxorubicin. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang. [ABSTRACT FROM AUTHOR]

Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca 2+ anomalies in N G -nitro- l -arginine methyl ester ( l -NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that l -NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. l -NAME compromised cardiomyocyte contractile and intracellular Ca 2+ properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca 2+ , elevated baseline and peak intracellular Ca 2+ . These l -NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by l -NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against l -NAME. These findings suggested that metallothionein protects against l -NAME-induced myocardial anomalies possibly through restoration of autophagy. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress, together with the unfolded protein response (UPR), is initially considered an adaptive response aiming at maintenance of ER homeostasis. Nonetheless, ER stress, when in excess, can eventually trigger cell apoptosis and loss of function. UPR is mediated by three major transmembrane proteins, including inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor (ATF) 6. A unique role has been speculated for ER stress in the pathogenesis of diabetes mellitus (DM) and its complications. Recent studies have shown that ER stress is an early event associated with diabetic cardiomyopathy, and may be triggered by hyperglycemia, free fatty acids (FFAs) and inflammation. In this mini-review, we attempted to discuss the activation machinery for ER stress in response to these triggers en route to disrupted ER function and cellular autophagy or apoptosis, ultimately insulin resistance and development of diabetic cardiomyopathy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial. Background: pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial. Methods: Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Results: Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p < 0.001) in minor adverse events (32 vs. 7), quantity of blood transfused, duration of the procedure, median hospital stay, median intensive care unit stay, median hospitalization cost, and median blood loss. During a median follow-up of 2 years, the left ventricular end-diastolic dimension of both groups returned to normal and there was no difference in closure rate, adverse events, and complications between groups. Conclusions: Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799) [Copyright &y& Elsevier]

Highlights: [•] We examined the effect of metallothionein on ER stress-induced heart dysfunction. [•] Metallothionein rescues against ER stress-induced cardiac dysfunction. [•] The beneficial effect of metallothionein was related to attenuated autophagy. [Copyright &y& Elsevier]

The ability of the 10-23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the Ktrans in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients. [ABSTRACT FROM AUTHOR]

This study was aimed to explore the anti-oxidative effect of active peptide (T8) isolated from yak milk residue on H 2 O 2 -induced damage in HUVEC cells. The results showed that peptide T8 increased superoxide dismutase (SOD) and glutathione reductase (GR) activities while decreased malondialdehyde (MDA) content and ROS of HUVEC cells in the H 2 O 2 -induced damage model. Flow cytometry assays showed that peptide T8 reduced H 2 O 2 -induced cell apoptosis. The protein expression levels of PARP and cleaved-Caspase 9 was increased by Western blot analysis in the H 2 O 2 -induced HUVEC cells. The ratio of Bax/Bcl-2 was increased, suggesting peptide T8 inhibits H 2 O 2 -induced in mitochondrial-dependant death. The protein expression levels of p-Nrf2 was increased in HUVEC cells and the expressions of Nrf2 target genes Keap1, Nrf2, HO-1 and NQO1 were modulated by peptide T8 treatments. Blocking Nrf2 activation by inhibitor ML385, the protective effect of peptide T8 on the H 2 O 2 -induced injury was partially reversed. Our results indicate that peptide T8 ameliorate H 2 O 2 -induced oxidative stress via Nrf2 pathway in HUVEC cells. [Display omitted] • The strong antioxidative peptide T8 was isolated from yak milk residue. • Peptide T8 reduced H 2 O 2 -induced damage in HUVEC cells. • Peptide T8 regulated antioxidation-related gene expressions via Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Background: Perimembranous ventricular septal defects (pmVSDs) are one of the most common forms of congenital cardiac malformation in children. Results of transcatheter pmVSD closure remain debatable, prompting the need for further evaluation with regard to the safety and efficacy of this procedure. The aim of the study was to analyze the safety, efficacy, and long-term follow-up data associated with transcatheter closure of pmVSDs in children using symmetric occluders. Methods: From December 2002 to October 2011, 525 children with pmVSDs between 2 and 12 years of age underwent transcatheter closure at three major heart centers in northwest China with symmetric pmVSD occluders. All patients were followed up until October 2011 with electrocardiogram and transthoracic echocardiography. Adverse events were recorded and evaluated. Results: There were 252 male and 273 female patients with an average weight of 21.5 kg. The mean age at the time of transcatheter closure was 5.6 years, and the average ratio of pulmonic to systemic blood flow was 2.5. Transcatheter intervention was successfully performed in 502 patients (95.6%). The median device size implanted was 6.5 mm (range, 4 to 18 mm). During a median 45-month follow-up period, no mortality occurred. A total of three major adverse events (0.6%) were reported; two were valve-related. Meanwhile, 104 minor adverse events were detected during the entire follow-up period. All individuals experiencing major adverse events were younger than 3 years of age. The incidence of major adverse events in patients younger than 3 years old was significantly higher than that of patients older than 3 years old (3.75% versus 0.00%; Fisher''s exact test p = 0.004). Conclusions: Data from the current study suggest that transcatheter pmVSD closure using symmetric occluders displayed an excellent success rate and long-term follow-up results. The transcatheter approach provides a less-invasive alternative to open surgery and displays some promise in the treatment of pmVSDs in certain patient populations. [Copyright &y& Elsevier]

Objectives: To evaluate the cerebral and myocardial protective effects of hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery bypass graft surgery. Design: A prospective, randomized, single-blinded study including patients scheduled for elective on-pump or off-pump surgery between December 2007 and February 2009. Setting: A tertiary care university teaching hospital. Participants: Forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients. Interventions: Patients were randomized to either the control (15 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) groups. Patients in the HBO groups underwent preconditioning for 5 days before surgery. Measurements and Main Results: On-pump coronary artery bypass graft surgery patients preconditioned with HBO had significant decreases in S100B protein, neuron-specific enolase, and troponin I perioperative serum levels compared with the on-pump control group. Postsurgically, patients in the on-pump HBO group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs. Serum catalase activity 24 hours postoperatively was significantly increased compared with the on-pump control group. In the off-pump groups, there was no difference in any of the same parameters. Conclusions: Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing on-pump coronary artery bypass graft surgery. No protective effects were noted in off-pump coronary artery bypass graft surgery. [ABSTRACT FROM AUTHOR]

Background: Cardiac ischemia-reperfusion injury after cardiopulmonary bypass contributes to postoperative morbidity and mortality in patients with open-heart surgery. This randomized controlled trial was designed to address the protective effects of electroacupuncture (EA) pretreatment on myocardial injury in patients undergoing heart valve replacement surgery. Methods: Sixty patients with acquired heart valve disease were randomly allocated to the EA pretreatment group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC 6), Lieque (LU 7), and Yunmen (LU 2) for 30 minutes each day for five consecutive days before surgery. Hemodynamic data, mechanical ventilation time, inotropic drug use in the intensive care unit, serum cardiac troponin I concentrations, morbidities, and mortalities were compared between the two groups. This trial is registered with ClinicalTrials.gov, number NCT00732459. Results: At 6 hours, 12 hours, and 24 hours after reperfusion, levels of serum cardiac troponin I were significantly decreased in the EA group (5.74 ± 0.67, 6.22 ± 0.66, and 5.21 ± 0.58) compared with that in the control group (7.89 ± 0.74, 8.34 ± 1.08, and 7.57 ± 0.89, p < 0.05). The EA pretreatment significantly reduced overall serum troponin I release at 6 hours, 12 hours, and 24 hours after aortic cross-clamp removal. Meanwhile, EA pretreatment also reduced the inotrope score at 12 hours, 24 hours, and 48 hours after the intensive care unit arrival and shortened intensive care unit stay time (p < 0.05). Conclusions: The present study demonstrated that EA pretreatment may alleviate cardiac ischemia-reperfusion injury in adult patients undergoing heart valve replacements. This simple and convenient treatment has the potential to be used in the clinic for reducing myocardial injury in patients with heart valve replacement surgery. [Copyright &y& Elsevier]

When an electrode (negative/positive) with excellent capacity matches a counter electrode with relatively low capacity or a pair of excellent electrodes cannot match each other, overall performance of the constructed supercapacitors (SCs) will be limited. Here, we report a novel electrode material 1,5-diamino-4,8-dihydroxyanthraquinone (DHAQ) grafted nitrogen-doped graphene aerogel (DHAQ-NGA) prepared by simple hydrothermal method. Since DHAQ molecule contains –C(=O)− and −NH−/−OH groups, the DHAQ-NGA composite can act as both the negative and positive electrode materials for a supercapacitor in ionic liquid electrolyte to improve capacity by faradaic reactions on these two electrodes. In addition, the intramolecular hydrogen bonding of DHAQ can improve the stability of the material. Therefore, DHAQ-NGA displays an enhanced specific capacity of 410 C g−1 for the positive electrode and 454 C g−1 for the negative electrode material. The assembled device can deliver a high energy density of 117 Wh kg−1 at a power density of 822 W kg−1. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Objectives: The purpose of this study was (1) to compare the fluoride release profile of an experimental composite to commercial GICs, resin-modified GICs, and composite resins; (2) to assess the fluoride release process. Methods: Commercial materials (n=3) were prepared according to manufacturers'' directions. The experimental composite (n=3) consisted of 78wt% filler and 22wt% resin. The resin consisted of 19wt% BisGMA, 38wt% UDMA, 19wt% TEGDMA, and 24wt% HEMA. Disc specimens were placed into 25ml of deionized water in sealed polyethylene vials and shaked at 1.4Hz at 37°C. Fluoride release was measured using a fluoride-ion specific electrode at different time intervals up to 284 days. Results: The fluoride release rate of the experimental composite demonstrated the highest rate of release within the first day (p=0.05), but decreased significantly by day 7. Release rates of the commercial glass-ionomer cements and resin-modified glass-ionomer cements thereafter were significantly higher than the experimental and commercial composites at p=0.05. Among the materials studied, cumulative fluoride release is adequately described by a two-term equation consisting of an initial fluoride release via a rapid dissolution process followed by a long-term diffusive release. Significance: An increase in the hydrophilicity of the polymer matrix through the introduction of HEMA improved the fluoride release over the short term during which dissolution occurs. Such a release behavior could be beneficial if it results in a fluoride reservoir that could be maintained by a prolonged slower release thereafter. [Copyright &y& Elsevier]

Due to the highly complex biological formation procedure, tumor is still difficult to be treated efficiently and always associated with proliferation, migration and inflammation during treatment. Herein, a novel strategy of boosted photocatalytic activity induced NAMPT-regulating therapy is used for tumors inhibition based on FK866 loaded bismuth-humic acids heterojunction (Bi-HA/FK866). With the reduction function of HA, Bi (Ⅲ) can be reduced to elemental Bi, which can be excited by NIR laser to form electron-hole pair due to the narrow bandgap. Moreover, the coated HA and Bi could form a heterojunction structure, which could decrease the electron–hole recombination, and further boost the photocatalytic activity, leading to highly efficient ROS generation and GSH depletion. The resulted ROS could induce DNA damage of the tumor cells, thus enhancing the sensitivity to the inhibitor of NAMPT (FK866) to downregulate NAD/ERK/NF-κB signal pathways, and eventually simultaneously prevent cancer progression. Moreover, the decreased NAD could downregulate NADPH and further suppress the innate antioxidant defense system by inhibiting reduction of GSSG. The boosted photocatalytic activity induced NAMPT-regulating therapy offers a promising way to address the important issue of penetration depth limitation induced cancer relapse and migration, providing more possibilities toward successful clinical application. [ABSTRACT FROM AUTHOR]

• The coupling of the Hp-NCL significantly increased in the slow gamma-band. • The coupling of the Hp-NCL only occurs in the turning area. • The interactions between the Hp and the NCL exist in the goal-directed behavior. • The predominant direction of information flow is from the Hp to the NCL. Avian hippocampus (Hp) and nidopallium caudolaterale (NCL) are believed to play key roles in goal-directed behavior. However, it is still unclear whether there are interactions between the two brain regions in the goal-directed behavior of pigeons. To investigate the interactions between the Hp and the NCL in the goal-directed behavior, we recorded local field potential (LFP) signals from the two regions simultaneously when the pigeons performed a goal-directed decision-making task. Amplitude-amplitude coupling analysis revealed that the coupling value between the LFP recorded from the Hp and that from the NCL increased significantly (P < 0.05) in slow gamma-band (40–60 Hz) during the turning area. In addition, the LFP functional network analysis demonstrated the LFP functional connections between the Hp and the NCL increased significantly (P < 0.05) in the turning area. The result of partial directed coherence (PDC) analysis showed that the predominant direction of information flow is thought to be from the Hp to the NCL. These findings suggest that there are causal functional interactions between the Hp and the NCL by which information is transmitted between the two regions relevant to goal-directed behavior. [ABSTRACT FROM AUTHOR]

Music emotion recognition (MER) is an important topic in music understanding, recommendation, retrieval and human computer interaction. Great success has been achieved by machine learning methods in estimating human emotional response to music. However, few of them pay much attention in semantic interpret for emotion response. In our work, we first train an interpretable model between acoustic audio and emotion. Filter, wrapper and shrinkage methods are applied to select important features. We then apply statistical models to build and explain the emotion model. Extensive experimental results reveal that the shrinkage methods outperform the wrapper methods and the filter methods in arousal emotion. In addition, we observed that only a small set of the extracted features have the key effects to arousal. While, most of our extracted features have small contribution to valence music perception. Ultimately, we obtain a higher average accuracy rate in arousal, compared to that in valence. [ABSTRACT FROM AUTHOR]

Abstract: An 8-year-old boy with a 3.8 mm perimembranous ventricular septal defect (PmVSD) and abnormal inferior vena cava return was attempted cardiac catheterization to occlude the VSD. Through the right jugular vein and right femoral artery approach, an 8 mm Amplatzer VSD occluder was successfully deployed under fluoroscopic and echocardiographic guidance. After a 2 year follow-up, the patient is symptom-free. Our report offers a new perspective to percutaneous treatment of PmVSD with abnormal inferior vena cava return. [Copyright &y& Elsevier]

In order to explore the effect of the C-terminal loop domain of Penicillium expansum lipase (PEL) on its regioselectivity and activity, homologous substitution and site-directed saturation mutagenesis were used. Two mutants PEL-loopAO and M234F were selected to catalyze the hydrolysis of tricaprylin and the molar ratios of 1,2-dicaprylin to 1,3-dicaprylin in the products were 25.57 and 8.57 respectively, showing obvious sn -1,3 regioselectivity of the mutants. Bioinformatics analysis showed that the structures of the substrate binding pocket of the mutants changed significantly. Moreover, due to the different positions of sn -1(3) and sn -2 ester bonds in the substrate molecule, it is easier for the substrate molecule to adapt to the significant changes in the substrate binding pocket and form the correct sn -1(3) catalytic conformation instead of sn -2 catalytic conformation, which makes the mutants exhibit apparent sn -1,3 position selectivity. In addition, the decrease of hydrophobicity of C-terminal loop domain will cause the decrease of lipase activity, whereas maintaining or improving the hydrophobicity can maintain or improve the activity. These findings are of great value in elucidating the relationship between the C-terminal loop domain of the lipase and its regioselectivity and activity, and also provide some reliable clues for obtaining lipases with better regioselectivity. [Display omitted] • Engineering PEL to obtain 1,3-positional selectivity. • C-terminal loop domain significantly affects enzyme activity. • Relationship between the loop domain and regioselectivity was researched. [ABSTRACT FROM AUTHOR]

• A fast hybrid dimensionality reduction method for classification is proposed. • Multi-strategy based feature selection is used to filter out irrelevant features. • Grouped feature extraction is used to remove redundancy among features. • The proposed method shows excellent efficiency and competitive classification performance. Dimensionality reduction is one basic and critical technology for data mining, especially in current "big data" era. As two different types of methods, feature selection and feature extraction each have their pros and cons. In this paper, we combine multi-strategy feature selection and grouped feature extraction and propose a novel fast hybrid dimension reduction method, incorporating their advantages of removing irrelevant and redundant information. Firstly, the intrinsic dimensionality of the data set is estimated by the maximum likelihood estimation method. Fisher Score and Information Gain based feature selection are used as multi-strategy methods to remove irrelevant features. With the redundancy among the selected features as clustering criterion, they are grouped into a certain amount of clusters. In every cluster, Principal Component Analysis (PCA) based feature extraction is carried out to remove redundant information. Four classical classifiers and representation entropy are used to evaluate the classification performance and information loss of the reduced set. The runtime results of different methods show that the proposed hybrid method is consistently much faster than the other three in almost all of the sets used. Meanwhile, the proposed method shows competitive classification performance, which has no significant difference basically compared with the other methods. The proposed method reduces the dimensionality of the raw data fast and it has excellent efficiency and competitive classification performance compared with the contrastive methods. [ABSTRACT FROM AUTHOR]

Several reports have demonstrated that Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1), which is transferred by extracellular vesicles (EVs) or exosomes, can promote cancer progression. However, its mechanism is still not fully understood. In the present study, we demonstrated that EV packaged LMP1 can activate normal fibroblasts (NFs) into cancer-associated fibroblasts (CAFs). The NF-κB p65 pathway is the key signal that promotes the activation of NFs to CAFs in nasopharyngeal carcinoma (NPC). In activated CAFs, aerobic glycolysis and autophagy were increased. Moreover, glucose uptake and lactate production were decreased, and mitochondrial activity in tumor cells was enhanced, which supported the Reverse Warburg Effect (RWE). During this process, upregulation of MCT4 in CAFs and MCT1 in tumor cells was observed. The NF-κB p65 pathway also plays an important role in the regulation of MCT4. Furthermore, co-culture with CAFs promoted the proliferation, migration and radiation resistance of NPC cells. And EV packaged LMP1 promoted tumor proliferation and pre-metastatic niche formation by activating CAFs in vivo. Our findings indicate that EV packaged LMP1-activated CAFs promote tumor progression via autophagy and stroma-tumor metabolism coupling. [ABSTRACT FROM AUTHOR]

Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells. [ABSTRACT FROM AUTHOR]

As one of important indicators of atherosclerosis (AS), excess homocysteine (Hcy), could cause oxidation stress, thus leading to inflammation and tissue damage. Hypochlorous acid/hypochlorite (HOCl/OCl−), as an important reactive oxygen species, is speculated to be an indicator of AS caused by Hcy-inducated. Here, a fluorescence nanoprobe LR NPs based on the assembly of pluronic F-127 and probe TR was developed for ClO− detection and imaging during Hcy stress. As expected, LR NPs showed good selectivity and sensitivity for ClO− detection. LR NPs can visualize the fluxes of HClO/ClO− during the stimulation of Hcy induce AS in real time, which demonstrated HClO/ClO− could be performed as an indicator of AS. [Display omitted] • A nano-fluorescent probe (LR NPs) with high sensitivity and selectivity to ClO− was designed and synthesized. • LR NPs was applied to detect endogenous and exogenous ClO− in living cells. • The fluorescent imaging of ClO− caused by Hcy-induced was reported for the first time. [ABSTRACT FROM AUTHOR]

[Display omitted] Starting with our previously reported work, a novel series of 3,4-dihydro-2 H -[1,4]oxazino[2,3- f ]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC 50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC 50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC 50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents. [ABSTRACT FROM AUTHOR]

We conducted this research to explore the role of latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) in modulating the DNA damage response (DDR) and its regulatory mechanisms in radioresistance. Our results revealed that LMP1 repressed the repair of DNA double strand breaks (DSBs) by inhibiting DNA-dependent protein kinase (DNA-PK) phosphorylation and activity. Moreover, LMP1 reduced the phosphorylation of AMP-activated protein kinase (AMPK) and changed its subcellular location after irradiation, which appeared to occur through a disruption of the physical interaction between AMPK and DNA-PK. The decrease in AMPK activity was associated with LMP1-mediated glycolysis and resistance to apoptosis induced by irradiation. The reactivation of AMPK significantly promoted radiosensitivity both in vivo and in vitro. The AMPKα (Thr172) reduction was associated with a poorer clinical outcome of radiation therapy in NPC patients. Our data revealed a new mechanism of LMP1-mediated radioresistance and provided a mechanistic rationale in support of the use of AMPK activators for facilitating NPC radiotherapy. [ABSTRACT FROM AUTHOR]

Unified venue representation is typically generated by integrating multi-modal information of micro-videos. It is also important to achieve reliable multi-modal fusion. In prior works, the reliability of decisions from multiple modalities is limited without the uncertainty estimation, which indicates whether or to what extent such decisions can be trusted. To this end, in this paper an attention-enhanced and trusted multimodal learning (AETML) model is proposed to achieve reasonable multimodal decision fusion for micro-video venue recognition. Specifically, a domain-adaptive visual transformer (VT) is used as the robust visual feature extractor. Denoise autoencoder and sentence2vector methods are applied to extract acoustic and textural features. Then, attention nets are devised to enhance the extracted features, and output class probabilities of each modality. An uncertainty estimation network is constructed to dynamically assess the reliability of such decisions, which are transformed into Dirichlet distribution for modeling the uncertainty. Lastly, trusted prediction results are yielded by integrating the adjusted distributions with uncertainty estimations according to the Dempster–Shafer evidence theory. The experimental results on a public micro-video dataset show that the proposed model outperforms the state-of-the-art methods. Further studies validate the effectiveness and robustness brought by the uncertainty estimation. [Display omitted] [ABSTRACT FROM AUTHOR]