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FMS-like receptor tyrosine kinase 3 (Flt3) expression was reported to increase in the heart in response to pathological stress, but the role of Flt3 activation and its underlying mechanisms remain poorly elucidated. This study was designed to investigate the role of Flt3 activation in sympathetic hyperactivity-induced cardiac hypertrophy and its mechanisms through autophagy and mitochondrial dynamics. In vivo, cardiac hypertrophy was established by subcutaneous injection of isoprenaline (6 mg/kg·day) in C57BL/6 mice for 7 consecutive days. The Flt3-ligand intervention was launched 2 h prior to isoprenaline each day. In vitro, experiments of cardiomyocyte hypertrophy, autophagy, and mitochondrial dynamics were performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that the expression level of Flt3 protein was significantly increased in the hypertrophic myocardium provoked by isoprenaline administration. Flt3-ligand intervention alleviated isoprenaline-induced cardiac oxidative stress, hypertrophy, fibrosis, and contractile dysfunction. Isoprenaline stimulation impaired autophagic flux in hypertrophic mouse hearts, supported by the accumulation of LC3II and P62 proteins, while Flt3-ligand restored the impairment of autophagic flux. Flt3 activation normalized the imbalance of mitochondrial fission and fusion in the hearts of mice evoked by isoprenaline as evidenced by the neutralization of elevated mitochondrial fission markers and reduced mitochondrial fusion markers. In NRCMs, Flt3-ligand treatment attenuated isoprenaline-stimulated hypertrophy, which was abolished by a Flt3-specific blocker AC220. Activating Flt3 reversed isoprenaline-induced autophagosome accumulation and impairment of autophagic flux probably by enhancing SIRT1 expression and consequently TFEB nuclear translocation. Flt3 activation improved the imbalance of mitochondrial dynamics induced by isoprenaline in NRCMs through the SIRT1/P53 pathway. Activation of Flt3 mitigated ISO-stimulated hypertrophy probably involves the restoration of autophagic flux and balance of mitochondrial dynamics. Therefore, activation of Flt3 attenuates isoprenaline-induced cardiac hypertrophy in vivo and in vitro, the potential mechanism probably attributes to SIRT1/TFEB-mediated autophagy promotion and SIRT1/P53-mediated mitochondrial dynamics balance. These findings suggest that activation of Flt3 may be a novel target for protection against cardiac remodeling and heart failure during sympathetic hyperactivity.

Neointimal hyperplasia is the major cause of carotid stenosis after vascular injury, which restricts the long-term efficacy of endovascular treatment and endarterectomy in preventing stenosis. Ginsenoside Re (Re) is a major active ingredient of ginseng having multifaceted pharmacological effects on the cardiovascular system, and is a potential treatment for restenosis. In this study, we demonstrated that Re treatment significantly inhibited vascular injury-induced neointimal thickening, reduced the intimal area and intima/media (I/M) ratio, increased the lumen area, and inhibited pro-inflammatory cytokines. In cultured A7R5 cells, Re inhibited LPS-induced proliferation and migration as evidenced by suppressed colony formation and shortened migration distance, accompanied by the downregulated expression of pro-inflammatory cytokines. Re promoted VSMC apoptosis induced by balloon injury in vivo and LPS challenge in vitro. Moreover, Re inhibited autophagy in VSMCs evoked by balloon injury and LPS as supported by reduced LC3II and increased p62 expressions. Suppression of autophagy with the specific autophagy inhibitor spautin-1 efficiently inhibited LPS-induced cell proliferation and inflammation and promoted caspase-3/7 activities. Mechanistically, we found that Re attenuated Ras/ERK1/2 expression in VSMCs in vivo and in vitro. The MEK1/2 inhibitor PD98059 showed similar effects to Re on cell proliferation, migration, apoptosis, and the levels of autophagy and cytokines. In conclusion, we provided significant evidence that Re inhibited vascular injury-induced neointimal thickening probably by promoting VSMC apoptosis and inhibiting autophagy via suppression of the Ras/MEK/ERK1/2 signaling pathway.

Vascular tree disentanglement and vessel type classification are two crucial steps of the graph-based method for retinal artery-vein (A/V) separation. Existing approaches treat them as two independent tasks and mostly rely on ad hoc rules (e.g. change of vessel directions) and hand-crafted features (e.g. color, thickness) to handle them respectively. However, we argue that the two tasks are highly correlated and should be handled jointly since knowing the A/V type can unravel those highly entangled vascular trees, which in turn helps to infer the types of connected vessels that are hard to classify based on only appearance. Therefore, designing features and models isolatedly for the two tasks often leads to a suboptimal solution of A/V separation. In view of this, this paper proposes a multi-task siamese network which aims to learn the two tasks jointly and thus yields more robust deep features for accurate A/V separation. Specifically, we first introduce Convolution Along Vessel (CAV) to extract the visual features by convolving a fundus image along vessel segments, and the geometric features by tracking the directions of blood flow in vessels. The siamese network is then trained to learn multiple tasks: i) classifying A/V types of vessel segments using visual features only, and ii) estimating the similarity of every two connected segments by comparing their visual and geometric features in order to disentangle the vasculature into individual vessel trees. Finally, the results of two tasks mutually correct each other to accomplish final A/V separation. Experimental results demonstrate that our method can achieve accuracy values of 94.7%, 96.9%, and 94.5% on three major databases (DRIVE, INSPIRE, WIDE) respectively, which outperforms recent state-of-the-arts.

PurposeThe purpose of this study is to generate diversified results for temporally ambiguous queries and the candidate queries are ensured to have a high coverage of subtopics, which are derived from different temporal periods.Design/methodology/approachTwo novel time-aware query suggestion diversification models are developed by integrating semantics and temporality information involved in queries into two state-of-the-art explicit diversification algorithms (i.e. IA-select and xQuaD), respectively, and then specifying the components on which these two models rely on. Most importantly, first explored is how to explicitly determine query subtopics for each unique query from the query log or clicked documents and then modeling the subtopics into query suggestion diversification. The discussion on how to mine temporal intent behind a query from query log is also followed. Finally, to verify the effectiveness of the proposal, experiments on a real-world query log are conducted.FindingsPreliminary experiments demonstrate that the proposed method can significantly outperform the existing state-of-the-art methods in terms of producing the candidate query suggestion for temporally ambiguous queries.Originality/valueThis study reports the first attempt to generate query suggestions indicating diverse interested time points to the temporally ambiguous (input) queries. The research will be useful in enhancing users’ search experience through helping them to formulate accurate queries for their search tasks. In addition, the approaches investigated in the paper are general enough to be used in many domains; that is, experimental information retrieval systems, Web search engines, document archives and digital libraries.

We performed a meta-analysis to evaluate the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. A systematic literature search up to October 2021 was done and 12 studies included 3555 subjects with closed incisions in orthopaedic trauma surgery at the start of the study: 1833 of them were provided with negative pressure wound therapy and 1722 were conventional wound dressings. They were reporting relationships about the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery using the dichotomous and continuous methods with a random or fixed-effect model. Negative pressure wound therapy had significantly lower deep surgical site infection (OR, 0.65; 95% CI, 0.48-0.88, P = .005), superficial surgical site infection (OR, 0.23; 95% CI, 0.11-0.49, P = .31), and wound dehiscence (OR, 0.41; 95% CI, 0.21-0.80, P = .009) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. However, negative pressure wound therapy had no significant effect on the length of hospital stay (MD, 0.29; 95% CI, -2.00- 2.58, P = .80) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Negative pressure wound therapy had significantly lower deep surgical site infection, superficial surgical site infection, and wound dehiscence; however, negative pressure wound therapy had no beneficial effect on the length of hospital stay compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Further studies are required to validate these findings.

Sorafenib, a multi-kinase inhibitor, is recommended as a new standard therapy for advanced hepatocellular carcinoma (HCC); however, it also exhibits severe cardiotoxicity and the toxicity mechanisms are not completely elucidated. Recent studies suggested that sorafenib-enhanced ROS may partially contribute to its anti-HCC effect, which implies that redox mechanism might also be involved in sorafenib's cardiotoxicity. In this study, we aimed to investigate if sorafenib is able to induce oxidative stress and how this may impair cellular functions in cardiomyocyte, ultimately accounting for its cardiotoxicity. Our results showed that in isolated rat hearts, sorafenib caused ventricular arrhythmias and left ventricular dysfunction, which were alleviated by the antioxidant N-(2-mercaptopropionyl)-glycine (MPG). In isolated ventricular myocytes, sorafenib increased diastolic intracellular Ca2+ levels, decreased Ca transients and the occurrence of Ca2+ waves. These changes were eliminated by MPG, CaMKII inhibitor KN-93 and the mitochondrial permeability transition pore (mPTP)inhibitor cyclosporin A (CsA). Moreover, the levels of oxidized and phosphorylated CaMKII were significantly increased. Sorafenib elevated ROS levels, which was reversed by CsA and MPG; additionally, sorafenib reduced the activity of mitochondrial complex III and augmented mitochondrial ROS production. In vivo rats treated with sorafenib exhibited a reduction of antioxidant defence and abnormal histological alterations including hypertrophy, increased fibrosis, disordered myofibrils and damaged mitochondria, which were protected by MPG. We conclude that sorafenib induces the disruption of Ca2+ homoeostasis and cardiac injury via enhanced ROS potentially through inhibiting mitochondrial complex III, the opening of mPTP and overactivating CaMKII. These results provide a potential strategy for preventing or reducing cardiotoxicity of sorafenib.

The fast-developing information technology has imposed urgent need for effective solutions to overcome the increasing power density in further scaled electronic devices and systems. The tunnel fiel...

Background This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). Methods Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden’s Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. Results For Golden’s interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden’s Stroop RT disappeared, but differences in Golden’s Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. Conclusions Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.

Highlights • We provide the possible methods for psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai. As we mentioned: an effective PCI surely requires the two-pronged approaches, online and onsite psychotherapy are recommended ., Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.

AIM FMS-like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action. METHODS In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL/6 mice. Flt3-specific ligand (FL) was administered intraperitoneally every two days (5 µg/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector-mediated overexpression of Flt3. RESULTS Our results demonstrated that following chronic Ang II infusion for 4 weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II-treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3-overexpressed H9c2 cells, FL attenuated Ang II-induced pathological autophagy and inactivated AMPK/mTORC1/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II. CONCLUSION Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK/mTORC1/FoxO3a-mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.

CT images scanned in arterial and venous phases have been demonstrated to provide complementary information for accurate pancreas segmentation. In this paper, we propose a novel multi-phase and multi-level selective feature fusion network (MMNet) with a core component named adaptive cross refinement (ACR) module. Specifically, MMNet adopts two parallel encoders to extract features of the two phases respectively, which are then fused by ACR to excel each complementarity advantage. Unlike most existing fusion methods which only exchange and combine features of a single level with the same resolution between two phases/modalities, ACR module intelligently aggregates features of all levels in one phase as a multi-level prior, and then adaptively selects the most effective information from the multi-level prior to refine features at each level of the other phase. Such multi-phase, multi-level selective feature exchange and fusion strategy is bi-directional to mutually benefit segmentation of both phases. Experimental results on 141 cases of our private dataset demonstrate the effectiveness of our ACR module and superior performance to the state-of-the-art fusion methods.

A series of mesoporous nano-MgO-ZrO2 with various Mg:Zr atomic ratios were prepared via simple co-precipitation process without addition of a template. It was demonstrated by XRD, N2 adsorption-desorption and TEM that these samples still kept well mesoporous structure even after calcination at 600 °C. During the preparation process, divalent Mg2+ ions could be incorporated into tetragonal ZrO2 lattice to form a solid solution. More important, the surface basic density of these catalysts closely depended on their Mg content. Then, the resulting MgO-ZrO2 catalysts were used as basic catalysts for the dipropyl carbonate (DPC) synthesis via transesterification of n-propanol and dimethyl carbonate. The relationship between the basic property of solid base and their catalytic performance was clarified in detail. Among all the materials, the catalyst with Mg:Zr atomic ratio = 0.5 showed the best catalytic performance. Under the suitable reaction conditions, the yield of DPC could reach 98.5% with 100% selectivity. In addition, based on the reusability test and catalyst characterization, this catalyst exhibited extraordinary structure stability and it could be reused at least four times without obvious loss of reactivity.

TiO2 compact layer (c-TiO2) is generally applied for high-efficiencies perovskite solar cells (MPSCs), but it shows a relatively low electron mobility, which may restrict some performance of the MPSCs. Herein, we demonstrated SnO2 compact layer (c-SnO2), which prepared by spray pyrolysis using a solution of dibutyltin bisacetylacetonate in ethanol, could be an excellent alternative compact layer for efficient hole-conductor-free printable MPSCs. The best device with such a c-SnO2 has achieved an efficiency of 13.77%, which is very comparable to that obtained by the device based on c-TiO2. Furthermore, the device with c-SnO2 showed less pronounced hysteresis effect, probably because of the higher electron mobility of SnO2 and less charge accumulation at the interfaces. The simple preparation process and improved hysteretic behavior pave the way for industrialization of PSCs.

BACKGROUND Compared with demography and symptomatology of schizophrenia, the treatment strategies1 and quality of life (QOL) for patients are of more urgent concern for the therapeutic alliance. OBJECTIVE The study aims to investigate the current situation and correlation of metabolic characteristics of male schizophrenics by measuring serum concentrations of cortisol and testosterone related with metabolic abnormalities in male schizophrenics. METHODS The 174 patients were grouped based on their risk of metabolic syndrome (MetS),into Non-MetS, High-risk-MetS (HR-MetS), or MetS groups. Multiple linear regression analysis was used to associate the correlations between WHO Quality of Life-BREF (WHOQOL-BREF) score and five metabolic indices (Body mass index (BMI), Mean arterial pressure (MAP), Cholesterol, Triglyceride and Fasting blood glucose (FBG)). Metabolic diseases were associated with cortisol and testosterone levels using Pearson’s correlations. RESULTS Compared to HR-MetS and MetS groups, the WHOQOL-BREF score in Non-MetS group has statistical difference. Multiple linear regression via stepwise analysis eventually constructed a regression model of WHOQOL-BREF score with four variables including MAP, IQ, FBG and age. The triglyceride level was positively correlated with the cortisol level while all the five metabolic indices were negatively correlated with the testosterone level. CONCLUSIONS In the five metabolic indices, the risks of hyperglycemia and hypertension are correlated with the quality of life in male schizophrenics rather than those of obesity or hyperlipidemia. The correlation analysis then showed that there was a weak linear correlation between testosterone level and all of the five metabolic indices.

OBJECTIVE: To characterize the traits of neuropsychological functioning deficits in patients with attention-deficit/ hyperactivity disorder (ADHD) with comorbid disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Twenty out-patients with ADHD, 20 with ADHD with comorbid DICCD, and 20 with DICCD, all aged 6-16 years, were enrolled in this study, with 20 healthy subjects matched for age, gender and IQ serving as the healthy controls. The patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Revision (DSM-5). All the subjects were assessed with Golden Stroop test and emotional Stroop test to evaluate their response inhibition and emotional responding. RESULTS: In Golden Stroop test, the interference scores (IGs) of errors and reaction time both differed significantly among the groups (P < 0.05), and were the highest in patients with ADHD only. In emotional Stroop test, the mean reaction time (MRT) showed significant differences among the groups (P < 0.05); the MRT of positive- congruent trials in ADHD with comorbid DICCD group was shorter than that in ADHD group but longer than that in group DICCD; the MRT in the 3 case groups were all longer than that in the control group. The MRT of both positive-incongruent trials and negative-congruent trials in ADHD with comorbid DICCD group and DICCD group was shorter than that in ADHD group but longer than that in the control group. The MRT of negative- incongruent trials in DICCD group was shorter than that in ADHD group and ADHD with comorbid DICCD group but longer than that in the control group. CONCLUSIONS: The response inhibition deficit and abnormal emotional responding are the core symptoms of ADHD. Bias emotional stimuli may render response inhibitory dysfunction in patients with DICCD with callous-unemotional traits of emotional responding disorder, especially in dealing with negative emotional trials, while the comorbidity of ADHD and DICCD tends to have the emotional response trait of DICCD.

A compact-layer-free, hole-conductor-free, fully printable mesoscopic perovskite solar cell presents a power conversion efficiency of over 13%, which is comparable to that of the device with a TiO2 compact layer. The different wettability of the perovskite precursor solution on the surface of FTO and TiO2 possesses a significant effect on realizing efficient mesoscopic perovskite solar cell. This result shows a promising future in printable solar cells by further simplifying the fabrication process and lowering the preparation costs.

To meet the challenge of continuously increasing global energy demands, organic-inorganic halide based perovskite solar cells (PSCs) have garnered great attention from the photovoltaic research community for their low cost and high efficiency. The efficiency of perovskite-based mesoscopic solar cells increases rapidly, from 3.8% in 2009 to 22.1% in 2016. N-type metal-oxide electron transport layer, as one of the important components in mesoscopic PSCs (MPSCs), acts as not only a scaffold layer for the growth of perovskite crystals, but also a layer to supply transfer pathways for electrons injected from perovskites. In this review, we discussed recent published reports of MPSCs with the focus on n-type metal-oxide electron transport layer in MPSCs. The scaffold materials, scaffold nanostructure, and scaffold/perovskite interface engineering are considered, and the effects of these modifications of scaffolds on the performance of MPSCs are summarized in this review.

A printing process for the fabrication of perovskite solar cells (PSCs) exhibits promising future application in the photovoltaic industry due to its low-cost and eco-friendly preparation. In mesoscopic carbon-based PSCs, however, compared to conventional ones, the hole-transport-layer-free PSCs often lead to inefficient hole extraction. Here, we used liquid metal (LM, Galinstan) as an interface modifier material in combination with a carbon electrode. Considering the high conductivity and room-temperature fluidity, it is found that LMs are superior in improving hole extraction and, more importantly, LMs tend to be reserved at the interface between ZrO2 and carbon for enhancing the contact property. Correspondingly, the carrier transfer resistance was decreased at the carbon/perovskite interface. As optimized content, the triple mesoscopic PSCs based on mixed-cation perovskite with a power conversion efficiency of 13.51% was achieved, involving a 26% increase compared to those without LMs. This work opens...