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Background Recent studies highlight the regulatory role of arachidonate lipoxygenase5 (Alox5) and its metabolite 5‐hydroxyeicosatetraenoic acid (5‐HETE) in cancer tumorigenesis and progression. In this study, we analyzed the expression, biological function and the downstream signaling of Alox5 in gastric cancer. Methods Alox5 protein levels were measured using IHC and ELISA. Growth, migration and survival assays were performed. Phosphorylation of molecules involved in growth and survival signaling were analyzed by WB. Analysis of variance and t‐test were used for statistic analysis. Results Alox5 and 5‐HETE levels were upregulated in gastric cancer patients. ALOX5 overexpression or 5‐HETE addition activates gastric cancer cells and reduces chemotherapy’s efficacy. In contrast, ALOX5 inhibition via genetic and pharmacological approaches suppresses gastric cancer cells and enhances chemotherapy’s efficacy. In addition, Alox5 inhibition led to suppression of ERK‐mediated signaling pathways whereas ALOX5‐5‐HETE activates ERK‐mediated signaling in gastric cancer cells. Conclusions Our work demonstrates the critical role of ALOX5‐5‐HETE in gastric cancer and provides pre‐clinical evidence to initialize clinical trial using zileuton in combination with chemotherapy for treating gastric cancer., Our work demonstrates that the ALOX5‐5‐HETE axis promotes gastric cancer growth and alleviates chemotherapy toxicity via MEK/ERK activation and provides pre‐clinical evidence to initialize clinical trials using zileuton in combination with chemotherapy for the treatment of gastric cancer.

The nanoporous (NP) GaN wafers which were fabricated by electrochemical etching (EC) method were used as substrates to deposit Er-doped Ga2O3 epitaxial films by pulsed layer deposition (PLD). The epitaxial relationship between the GaN and Er doped β-Ga2O3 film was Ga2O3 (−201) ‖ GaN (0001) with Ga2O3 [010] ‖ GaN [-12-10]. Compared to the Er doped films on the epi-GaN wafers with the porosity of 0%, ~20% and ~60%, the β-Ga2O3 film deposited on the wafer with a porosity of ~40%, which has an energy bandgap of ~4.89 eV, has the best crystal quality and optoelectronic properties. The performance enhancement should be due to improved crystalline quality as a result of the existence of nanopores in the etched substrates. The excellent properties of Er doped Ga2O3 films indicated that the films have great potential to fabricate Ga2O3 optoelectronic devices.

Pulmonary hypertension due to left heart disease (PH-LHD) is the most prevalent type of pulmonary hypertension (PH). The hemodynamic diagnostic standard of pulmonary arterial wedge pressure (PAWP)15 mm Hg that is traditionally recommended by guidelines is being challenged.To address this problem, we analyzed the data of 154 patients with PH-LHD admitted to our center from April 2013 to March 2018. Pharmacological or nonpharmacological treatment of underlying left heart disease was offered to all 154 patients.In total, there were 24 patients (15.6%) with PAWP ≤15 mm Hg. Comparison of echocardiography and right heart catheterization parameters between the two groups (PAWP15 mm Hg and PAWP ≤15 mm Hg) showed that the group with PAWP ≤15 mm Hg had smaller left ventricular diameter, higher cardiac output, lower pressure and higher oxygen saturation in the pulmonary artery, right atrium, right ventricle, and superior vena cava. No significant difference was found regarding dilated cardiomyopathy, diabetes mellitus, hypertension, atrial fibrillation, and left heart valvular disease, but a significant difference was found for coronary heart disease (higher morbidity in group with PAWP ≤15 mm Hg) between the two groups.We found that 15.6% of the patients with PH-LHD under pharmacological or nonpharmacological treatment had PAWP ≤15 mm Hg. These results suggest that the diagnostic criterion of PAWP and the characteristics for this group of patients should be further investigated.HINTERGRUND: Eine pulmonale Hypertonie aufgrund einer Linksherzerkrankung (PH-LHD) stellt den Typ der pulmonalen Hypertonie (PH) mit der höchsten Prävalenz dar. Der bisher in Leitlinien empfohlene Standard der hämodynamischen Diagnostik mit einem pulmonalarteriellen Wedge-Druck (PAWP)15 mm Hg wird nun infrage gestellt.Zur Klärung dieser Frage wurden die Daten von 154 Patienten mit PH-LHD untersucht, die zwischen April 2013 und März 2018 in die Klinik der Autoren aufgenommen wurden. Allen 154 Patienten wurde eine pharmakologische oder nichtpharmakologische Therapie der zugrunde liegenden Herzerkrankung angeboten.Bei 24 Patienten (15,6%) lag ein PAWP ≤15 mm Hg vor. Im Vergleich von Parametern der Echokardiographie und der Rechtsherzkatheteruntersuchung zwischen den beiden Gruppen (PAWP15 mm Hg und PAWP ≤15 mm Hg) zeigte sich, dass die Gruppe mit PAWP ≤15 mm Hg einen kleineren linksventrikulären Durchmesser, höheren kardialen Output, niedrigeren Druck und höhere Sauerstoffsättigung in der Pulmonalarterie, im rechten Vorhof, rechten Ventrikel und der V. cava superior aufwies. Es bestand kein signifikanter Unterschied in Bezug auf dilatative Kardiomyopathie, Diabetes mellitus, Hypertonie, Vorhofflimmern und Linksherzklappenerkrankungen, aber es gab einen signifikanten Unterschied bei der koronaren Herzkrankheit (höhere Morbidität in der Gruppe mit PAWP ≤15 mm Hg) zwischen den beiden Gruppen.Es stellte sich heraus, dass 15,6% der Patienten mit PH-LHD unter pharmakologischer oder nichtpharmakologischer Therapie einen PAWP ≤15 mm Hg aufwiesen. Diese Ergebnisse sind ein Hinweis darauf, dass das diagnostische Kriterium des PAWP und die Eigenschaften dieser Patientengruppe weiter untersucht werden sollten.

Multiple sclerosis (MS) is a neurological disorder characterized by loss of the myelin sheath. Since the myelin sheath could insulate nerve fibers from the surrounding environment, its loss would result in dysfunction of the affected neurons in transmitting electrical signals, thus leading to sensation and motor disabilities. The treatment of MS is accompanied by a low treatment efficacy due to the existence of the blood-brain barrier (BBB) and occurrence of side effects due to a poor targeting efficacy. To overcome these obstacles of traditional MS treatment methods, nanomedicines have recently been employed to deliver MS therapeutic agents to the lesions. With deep BBB penetration and specific targeting, these nano-based interventions have received positively encouraging results and become another potential MS treatment method with better therapeutic outcomes. This review will focus on recent advances in nanomedicines for the treatment of MS by critically analyzing their strengths and weaknesses. We will propose perspectives on the development of these MS therapeutic nanomaterials.

High recurrence and metastasis of triple-negative breast cancer (TNBC) after operation is a leading cause of breast cancer related death. The pre-metastatic niche (PMN) is an environment in a secondary organ conducive to the metastasis of a primary tumor. Herein, we identify exosomes from autologous breast cancer cells that show effective lung targeting ability. Based on this, we developed the biomimetic nanoparticles (cationic bovine serum albumin (CBSA) conjugated siS100A4 and exosome membrane coated nanoparticles, CBSA/siS100A4@Exosome) to improve drug delivery to the lung PMN. CBSA/siS100A4@Exosome self-assembled nanoparticles formed homogeneous sizes of ~200 nm, protected siRNA from degradation, and showed excellent biocompatibility. Further in vivo studies showed that CBSA/siS100A4@Exosome had a higher affinity toward lung in comparison to the CBSA/siS100A4@Liposome, and exhibited outstanding gene-silencing effects that significantly inhibited the growth of malignant breast cancer cells. Taken together, these results indicate that CBSA/siS100A4@Exosome self-assembled nanoparticles are a promising strategy to suppress postoperative breast cancer metastasis.

PurposeHeart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodeling and heart failure after MI, as well as the molecular mechanisms involved.MethodsMale C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilized to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0–3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analyzed by qRT–PCR, and protein expression changes were assessed by Western blotting.ResultsOur findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro.Conclusion CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer.

Coronary heart disease is a serious disease that endangers human health and life. In recent years, the incidence and mortality of coronary heart disease have increased rapidly. The quantification of the coronary artery is critical in diagnosing coronary heart disease. In this paper, we improve the coronary arteries segmentation performance from two aspects of network model and algorithm. We proposed a U-shaped network based on spatio-temporal feature fusion structure to segment coronary arteries from 2D slices of computed tomography angiography (CTA) heart images. The spatio-temporal feature combines features of multiple levels and different receptive fields separately to get more precise boundaries. It is easy to cause over-segmented for the small proportion of coronary arteries in CTA images. For this reason, a combo loss function was designed to deal with the notorious imbalance between inputs and outputs that plague learning models. Input imbalance refers to the class imbalance in the input training samples. The output imbalance refers to the imbalance between the false positive and false negative of the inference model. The two imbalances in training and inference were divided and conquered with our combo loss function. Specifically, a gradient harmonizing mechanism (GHM) loss was employed to balance the gradient contribution of the input samples and at the same time punish false positives/negatives using another sensitivity–precision loss term to learn better model parameters gradually. Compared with some existing methods, our proposed method improves the segmentation accuracy significantly, achieving the mean Dice coefficient of 0.87. In addition, accurate results can be obtained with little data using our method. Code is available at: https://github.com/Ariel97-star/FFNet-CoronaryArtery-Segmentation . Our method can intelligently capture coronary artery structure and achieve accurate flow reserve fraction (FFR) analysis. Through a series of steps such as CPR curved reconstruction, the detection of coronary heart disease can be achieved without affecting the patient’s body. In addition, our work can be used as an effective means to assist in the detection of stenosis. In the screening of coronary heart disease among high-risk cardiovascular factors, automatic detection of luminal stenosis can be performed based on the application of later algorithm transformation.

Mangiferin is the major bioactive ingredient in the leaves of Mangifera indica L., Aqueous extract of such leaves have been traditionally used as an indigenous remedy for respiratory diseases including cough and asthma in Traditional Chinese Medicine. Mangiferin was shown to exert its anti-asthmatic effect by modulating Th1/Th2 cytokines imbalance via STAT6 signaling pathway. However, compelling evidence indicated that subtypes of T helpers and regulatory T cells other than Th1/Th2 were also involved in the pathogenesis of asthma. In current study, we investigated the effects of mangiferin on the differentiation and function of Th9, Th17 and Treg cells in a chicken egg ovalbumin (OVA)-induced asthmatic mouse model. Mangiferin significantly attenuated the symptoms of asthma attacks, reduced the total number of leukocytes, EOS and goblet cells infiltration in lung. Simultaneously, treatment with mangiferin remarkably decreased the proportion of Th9 and Th17 cells; reduced the levels of IL-9, IL-17A; inhibited the expression of PU.1 and RORγt in lung. However, the proportion of Treg cells, the expression of IL-10, TGF-β1 and Foxp3 were increased by mangiferin. Our data suggest that mangiferin exerted anti-asthmatic effect through decreasing Th9 and Th17 responses and increasing Treg response in OVA-induced asthmatic mouse model.

Background Blood-brain barrier (BBB) disruption plays a key role in the pathophysiology of acute ischemic stroke. Matrix metalloproteinases-2/9 (MMP-2/9) have been shown to participate in the disruption of the BBB and hemorrhagic transformation after cerebral ischemia. Toll-like receptor 2 (TLR2) may also be correlated with endothelial cell injury during ischemia-reperfusion events. However, the correlation between MMP-2/9 and TLR2 on endothelial cells after ischemia has not yet been evaluated. The aim of the study was to evaluate the impact of TLR2 and MMP-2/9 on tight junction proteins (TJs) after oxygen–glucose deprivation and reoxygenation (OGDR). Materials and methods Rat primary brain microvascular endothelial cells (BMECs) were cultured. Quantitative real-time PCR and western blotting were used to measure the mRNA and proteins expression of TLR2 and MMP-2/-9. The protein expression of TJs was detected by western blotting and immunofluorescence. Results MMP-9 significantly increased after OGDR. Protein and mRNA expression of TLR2 was also upregulated. However, claudin-5, occludin, collagen-Ⅳ, and ZO-1 were decreased after OGDR. When monoclonal anti-TLR2 antibody (T2.5) was added to BMECs after OGDR, MMP-9 was significantly downregulated, whereas occludin and collagen-Ⅳ had a tendency to increase. Conclusion TLR2 antagonist T2.5 is able to downregulate the expression of MMP-9, and may constitute a therapeutic option for restoration of the BBB after OGDR.

Metformin, a clinical agent of type 2 diabetes, is reported as a potential geroprotector. Viral infection induces phenotypes of senescence in human T cells, and polyinosinic:polycytidylic acid (poly I:C), a viral mimic, induces upregulation of senescence-associated beta-galactosidase (SA-β-gal) activity in the ovary of the annual fish Nothobranchius guentheri. However, the effects and mechanisms of metformin on poly I:C-induced aging-like phenomena are poorly understood in vertebrates. In this study, the activity of SA-β-gal increased in the gut of 12-month-old fish and poly I:C-injected 6-month-old fish, compared to 6-month-old control fish, indicating that poly I:C induces aging-like phenomena in the gut of the fish. Metformin supplementation retarded accumulation of SA-β-gal in the gut of old fish and poly I:C-treated young fish. The results of qPCR analysis showed that metformin reduced NF-κB-mediated inflammatory response including the decreased level of proinflammatory cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in the gut of the fish with natural aging and poly I:C-injected 6-month-old fish. Metformin also exhibited antioxidant effects, as it reduced reactive oxygen species production that is associated with the upregulation of FoxO3a and PGC-1α in the gut of 6-month-old fish with poly I:C injection. Expression of AMPK and SIRT1 was reduced in the gut of 6-month-old fish with poly I:C treatment, and feeding metformin reversed these declines. Taken together, the present study suggested that poly I:C injection led to aging-like phenomena in the gut and metformin activated AMPK and SIRT1 to reduce NF-κB-mediated inflammation and resist oxidative stress via enhanced expression of FoxO3a and PGC-1α and finally delayed gut aging in vertebrates.

Cognitive impairment is one of the primary features of vascular dementia (VD). However, the specific mechanism underlying the regulation of cognition function in VD is not completely understood. The present study aimed to explore the effects of microRNA (miR)-150 on VD. To determine the effects of miR-150 on cognitive function and hippocampal neurons in VD model rats, rats were subjected to intracerebroventricular injections of miR-150 antagomiR. The Morris water maze test results demonstrated that spatial learning ability was impaired in VD model rats compared with control rats. Moreover, compared with antagomiR negative control (NC), miR-150 antagomiR alleviated cognitive impairment and enhanced memory ability in VD model rats. The triphenyltetrazolium chloride, Nissl staining and immunohistochemistry results further demonstrated that miR-150 knockdown improved the activity of hippocampal neurons in VD model rats compared with the antagomiR NC group. To validate the role of miR-150 in neurons in vitro, the PC12 cell line was used. The flow cytometry and Hoechst 33342/PI double staining results indicated that miR-150 overexpression significantly increased cell apoptosis compared with the mimic NC group. Moreover, the dual-luciferase reporter gene assay results indicated that miR-150 targeted HOXA1 and negatively regulated HOXA1 expression. Therefore, the present study indicated that miR-150 knockdown ameliorated VD symptoms by upregulating HOXA1 expression in vivo and in vitro.

Acute gut graft-versus-host disease (aGVHD) is a leading threat to the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Abnormal gut microbiota is correlated with poor prognosis in allo-HSCT recipients. A disrupted intestinal microenvironment exacerbates dysbiosis in GVHD patients. We hypothesized that maintaining the integrity of the intestinal barrier may protect gut microbiota and attenuate aGVHD. This hypothesis was tested in a murine aGVHD model and an in vitro intestinal epithelial culture. Millipore cytokine array was utilized to determine the expression of proinflammatory cytokines in the serum. The 16S rRNA sequencing was used to determine the abundance and diversity of gut microbiota. Combining Xuebijing injection (XBJ) with a reduced dose of cyclosporine A (CsA) is superior to CsA alone in improving the survival of aGVHD mice and delayed aGVHD progression. This regimen also reduced interleukin 6 (IL-6) and IL-12 levels in the peripheral blood. 16S rRNA analysis revealed the combination treatment protected gut microbiota in aGVHD mice by reversing the dysbiosis at the phylum, genus, and species level. It inhibited enterococcal expansion, a hallmark of GVHD progression. It inhibited enterococcal expansion, a hallmark of GVHD progression. Furthermore, Escherichia coli expansion was inhibited by this regimen. Pathology analysis revealed that the combination treatment improved the integrity of the intestinal tissue of aGVHD mice. It also reduced the intestinal permeability in aGVHD mice. Besides, XBJ ameliorated doxorubicin-induced intestinal epithelial death in CCK-8 assay. Overall, combining XBJ with CsA protected the intestinal microenvironment to prevent aGVHD. Our findings suggested that protecting the intestinal microenvironment could be a novel strategy to manage aGVHD. Combining XBJ with CsA may reduce the side effects of current aGVHD prevention regimens and improve the quality of life of allo-HSCT recipients.

Cognitive decline is a common clinical symptom in Parkinson's disease (PD) patients. Fluoxetine (FLU), a selective serotonin reuptake inhibitor, can improve cognitive deficits in demented patients. The present study investigated the effects of FLU on spatial learning and memory cognitions in 6-OHDA lesioned rats. Morris water maze (MWM) test showed that FLU significantly improved spatial cognitive deficits in rats with unilateral 6-OHDA injection at 4 and 7 weeks after 6-OHDA injection. Electrophysiological recordings demonstrated that the number and duration of high voltage spindles(HVSs)in the ipsilateral hippocampus of 6-OHDA lesioned rats were decreased by the administration of FLU. Furthermore, the spectral analysis of per frequency revealed increases in δ and θ rhythm power and decreases in α, β and γ rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats in contrast to the saline-treated rats. Acute FLU treatment can reduce δ and θ rhythm power, and enhance α, β and γ rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats. These findings suggest that FLU improves impaired cognition by tuning oscillatory activities in the hippocampus of 6-OHDA lesioned rats.

Hyperspectral imaging (HSI) emerges as a non-destructive and rapid analytical tool for assessing food quality, safety, and authenticity. This work aims to investigate the potential of combining the spectral and spatial features of HSI data with the aid of deep learning approach for the pixel-wise classification of food products. We applied two strategies for extracting spatial-spectral features: (1) directly applying three-dimensional convolution neural network (3-D CNN) model, (2) first performing principal component analysis (PCA) and then developing 2-D CNN model from the first few PCs. These two methods were compared in terms of efficiency and accuracy, exemplified through two case studies, i.e., classification of four sweet products and differentiation between white stripe (&ldquo, myocommata&rdquo, ) and red muscle (&ldquo, myotome&rdquo, ) pixels on salmon fillets. Results showed that combining spectral-spatial features significantly enhanced the overall accuracy for sweet dataset, compared to partial least square discriminant analysis (PLSDA) and support vector machine (SVM). Results also demonstrated that spectral pre-processing techniques prior to CNN model development can enhance the classification performance. This work will open the door for more research in the area of practical applications in food industry.

Time series spectral imaging facilitates a comprehensive understanding of the underlying dynamics of multi-component systems and processes. Most existing classification strategies focus exclusively on the spectral features and they tend to fail when spectra between classes closely resemble each other. This work proposes a hybrid approach of principal component analysis (PCA) and deep learning (i.e., long short-term memory (LSTM) model) for incorporating and utilizing the combined multi-temporal and spectral information from time series spectral imaging datasets. An example data, consisting of times series spectral images of casein-based biopolymers, was used to illustrate and evaluate the proposed hybrid approach. Compared to using partial least squares discriminant analysis (PLSDA), the proposed PCA-LSTM method applying the same spectral pretreatment achieved substantial improvement in the pixel-wise classification (i.e., accuracy increased from 59.97% of PLSDA to 85.73% of PCA-LSTM). When projecting the pixel-wise model to object-based classification, the PCA-LSTM approach produced an accuracy of 100%, correctly classifying the whole 21 film samples in the independent test set, while PLSDA only led to an accuracy of 80.95%. The proposed method is powerful and versatile in utilizing distinctive characteristics of time dependencies from multivariate time series dataset, which could be adapted to suit non-congruent images over time sequences as well as spectroscopic data. ispartof: ANALYTICA CHIMICA ACTA vol:1143 pages:9-20 ispartof: location:Netherlands status: published

Legumes are the second most important family of crop plants. One defining feature of legumes is their unique ability to establish a nitrogen-fixing root nodule symbiosis with soil bacteria known as rhizobia. Since domestication from their wild relatives, crop legumes have been under intensive breeding to improve yield and other agronomic traits but with little attention paid to the belowground symbiosis traits. Theoretical models predict that domestication and breeding processes, coupled with high-input agricultural practices, might have reduced the capacity of crop legumes to achieve their full potential of nitrogen fixation symbiosis. Testing this prediction requires characterizing symbiosis traits in wild and breeding populations under both natural and cultivated environments using genetic, genomic, and ecological approaches. However, very few experimental studies have been dedicated to this area of research. Here, we review how legumes regulate their interactions with soil rhizobia and how domestication, breeding and agricultural practices might have affected nodulation capacity, nitrogen fixation efficiency, and the composition and function of rhizobial community. We also provide a perspective on how to improve legume-rhizobial symbiosis in sustainable agricultural systems.

Dendritic polymers have highly branched three-dimensional architectures, the fourth type apart from linear, cross-linked, and branched one. They possess not only a large number of terminal functional units and interior cavities, but also a low viscosity with weak or no entanglement. These features endow them with great potential in various biomedicine applications, including drug delivery, gene therapy, tissue engineering, immunoassay and bioimaging. Most review articles related to bio-related applications of dendritic polymers focus on their drug or gene delivery, while very few of them are devoted to their function as cancer diagnosis agents, which are essential for cancer treatment. In this review, we will provide comprehensive insights into various dendritic polymer-based cancer diagnosis agents. Their classification and preparation are presented for readers to have a precise understanding of dendritic polymers. On account of physical/chemical properties of dendritic polymers and biological properties of cancer, we will suggest a few design strategies for constructing dendritic polymer-based diagnosis agents, such as active or passive targeting strategies, imaging reporters-incorporating strategies, and/or internal stimuli-responsive degradable/enhanced imaging strategies. Their recent applications in in vitro diagnosis of cancer cells or exosomes and in vivo diagnosis of primary and metastasis tumor sites with the aid of single/multiple imaging modalities will be discussed in great detail. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Diagnostic Tools > in vitro Nanoparticle-Based Sensing.

Purpose To investigate the effect of biospray dressing on the extent of eosinophil infiltration in the nasal mucosa and the level of serum IgE in experimental allergic rhinitis with nasal provocation. Method Twenty-four BALB/c mice were randomly divided into the normal control group, allergic rhinitis (AR) group, dexamethasone (DEX) treatment group, and biospray dressing (BD) group. The mice in the latter 3 groups were prepared for animal models of AR according to standard protocols. Mice in the BD group were administered a nasal spray before the nasal provocation, and those in the DEX group were administered an intraperitoneal injection of DEX. The nasal mucosa and serum were collected from each group. Nasal mucosa eosinophil infiltration was evaluated using hematoxylin and eosin staining, and enzyme-linked immunosorbent assay (ELISA) was performed to analyze the serum IgE expression. Results Eosinophil infiltration (AR vs BD P = .009) in the nasal mucosa and serum IgE expression (AR vs BD P = .001) were significantly lower in the BD group than in the AR group. There were no significant differences in the extent of eosinophil infiltration in the nasal mucosa or serum IgE expression between the BD and DEX groups. Conclusion Biospray dressings can significantly reduce allergen provocation in the nasal cavity and have a protective effect on the nasal mucosa. They can be used for the prevention and treatment of AR.

Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of C. albicans in kidneys. Although XBJ did not inhibit the growth and the virulence of C. albicans in vitro, it enhanced the viability of 293T cells upon C. albicans insults. Further RNA-seq analysis revealed that XBJ activated the endoplasmic reticulum (ER) stress pathway upon C. albicans infection. Western blot confirmed that XBJ maintained the expression of GRP78 in the presence of C. albicans. Interestingly, key active ingredients in XBJ (C0127) mirrored the effects of XBJ. C0127 not only rescued mice from lethal Candida sepsis and prevented the colonization of C. albicans in kidneys, but also sustained the survival of kidney epithelial cells partially by maintaining the expression of GRP78. These results suggested that XBJ may prevent fungal infection in sepsis patients. Pre-activation of ER stress pathway is a novel strategy to control C. albicans infection. Network pharmacology may accelerate drug development in the field of infectious diseases.

Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R) was positively correlated with decreased WM volume in the bilateral SMAs, whereas illness duration was negatively correlated with WM volume reduction in the right SMA. This study provides a thorough profile of WM volume loss in ALS and robust evidence that ALS is a multisystem neurodegenerative disease that involves a variety of subcortical WM tracts extending beyond motor cortex involvement.

According to the Chinese Pharmacopoeia (2015 edition), human physiology and drug administration are the major factors related to adverse reactions to traditional Chinese medicine (TCM). To promote the research and supervision of TCM, particularly the toxic medicines, the risk factors of the two aspects were first summarized. Risk factors from a drug and its administration include misidentification of herbs, improper processing, overdose, long duration of administration, inappropriate diagnosis, inappropriate combining of herbs, and contamination from microorganisms/heavy metals. Risk factors from the human body involve physiology, pathology, and genetics. The authors analyzed the positive and negative effects from classic applications of toxic Chinese herbs (e.g., Aconite spp., Aristolochia spp., Polygonum multiflorum, Realgar spp., and Tripterygium wilfordii). Furthermore, for the rational use of these toxic Chinese medicines, some common chemical substances were discussed as well as the associated toxic mechanisms of them, and then summarized the traditional and modern methods of effective detoxification. It was reported that alkaloids, glycosides, toxic proteins, polypeptides, amino acids, tannins, anthraquinones, phenols, organic acids, terpenes, lactones, and heavy metal contamination were related to TCM toxicity. Meanwhile, some methodological studies (represented by network pharmacology and network toxicology) on the toxicity of TCM were discussed. Finally, a systematic evaluation strategy for toxic Chinese medicines was proposed. Overall, once the clinical side effects of herbal medicine are discovered and validated, a systematic study from the chemical substances to the toxicological mechanism should be conducted to solve the toxicity problems.

The poor outcomes in ovarian cancer necessitate new treatments. Strategies to interfere with oxidative phosphorylation have been recently highlighted for the treatment of ovarian tumors. Atovaquone, an approved antimicrobial drug, has demonstrated anti-cancer potential and ability in disrupting mitochondrial function. Here, we investigated the efficacy of atovaquone as single drug and its combination with cisplatin in ovarian cancer. We show that atovaquone at clinically achievable concentrations is active against ovarian cancer bulky and stem-cell like cells via inhibiting growth and colony formation, and inducing caspase-dependent apoptosis. In contrast, atovaquone either does not or inhibits normal cells in a less extent than in ovarian cancer cells. Mechanism studies using multiple independent approaches demonstrate that atovaquone acts on ovarian cancer cells via decreasing mitochondrial complex III which results in mitochondrial respiration inhibition, energy reduction and oxidative stress. In line with in vitro findings, atovaquone alone at non-toxic dose is effective in inhibiting ovarian cancer growth in vivo, and its combination with cisplatin is synergistic. Our study suggests that atovaquone is a promising candidate to the treatment of ovarian cancer. Our work also supports the notion that mitochondrial respiration is a therapeutic target in ovarian cancer.

Epilepsy is a chronic neurological disorder affecting approximately 0.5-2% of the population worldwide. Gentamicin (GM) is an aminoglycoside antibiotic used to treat several types of bacterial infections. We investigate whether the administration of GM can reduce seizures in temporal lobe epilepsy (TLE).The animal model of temporal lobe epilepsy (TLE) was established by kainic acid (KA) intrahippocampal injection. Behavioral test and Electroencephalography (EEG) recordings were performed to detect the effects of GM on the seizures triggered by KA injection in rats. Furthermore, immunofluorescence was used to investigate the influence of GM on the c-fos expression in the hippocampus. Here we found that the intracerebroventricular administration of GM is able to prevent the seizures induced by intrahippocampal kainic acid (KA) injection. Behaviorally, the latent period to the first seizure was significantly prolonged by GM. GM can totally abolish the occurrence of stage IV or V seizures and prominently reduce the total seizure duration. Electrographic recording showed that the latent period to the first seizure, the number and duration of high-amplitude, high-frequency discharges were remarkably reduced by GM. Additionally, the expression of c-fos was significantly decreased in the ipsilateral hippocampus of KA-injected rats treated with GM compared with KA-injected rats treated with saline. These findings could promote the understanding of the pharmacological effects of GM, enriching the application of gentamicin in clinical practice.

We investigated the feasibility and potentiality of presymptomatic detection of tobacco disease using hyperspectral imaging, combined with the variable selection method and machine-learning classifiers. Images from healthy and TMV-infected leaves with 2, 4, and 6 days post infection were acquired by a pushbroom hyperspectral reflectance imaging system covering the spectral range of 380–1023 nm. Successive projections algorithm was evaluated for effective wavelengths (EWs) selection. Four texture features, including contrast, correlation, entropy, and homogeneity were extracted according to grey-level co-occurrence matrix (GLCM). Additionally, different machine-learning algorithms were developed and compared to detect and classify disease stages with EWs, texture features and data fusion respectively. The performance of chemometric models with data fusion manifested better results with classification accuracies of calibration and prediction all above 80% than those only using EWs or texture features; the accuracies were up to 95% employing back propagation neural network (BPNN), extreme learning machine (ELM), and least squares support vector machine (LS-SVM) models. Hence, hyperspectral imaging has the potential as a fast and non-invasive method to identify infected leaves in a short period of time (i.e. 48 h) in comparison to the reference images (5 days for visible symptoms of infection, 11 days for typical symptoms).

Focal ischemic stroke can lead to brain damage and cause human disability and death. Increased excitatory transmission and reduced neuronal inhibition are important pathological alterations in the cerebral ischemia, which can induce abnormal brain excitability. Nav1.6 is a key determinant of neuronal excitability in the nervous system. Here we investigate the expression of Nav1.6 at protein and mRNA levels in the rats subjected to middle cerebral artery occlusion (MCAO). Nav1.6 expression at mRNA levels in the ischemic and contralateral hemispheres of MCAO rats were persistently decreased at 6h, 12h and 24h after reperfusion compared to the sham-operated rats. However, a prominent, dynamic increase of Nav1.6 immunoreactivity in reactive astrocytes was observed in the genu of corpus callosum (GCC) of MCAO rats in the acute phase, reaching the peak at 6h after reperfusion, rapidly dropping at 12h and 24h after reperfusion. Furthermore, the upregulation of Nav1.6 expression was strongly correlated with the severity of reactive astrogliosis. Collectively, these findings suggest that this upregulated astrocytic sodium channel expression in the GCC of MCAO rats may contribute to the functional roles of reactive astrocytes in response to brain ischemia.

Background: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

// Yan Lv 1, * , Meng Si 2, * , Nannan Chen 3, * , Ya Li 3, * , Xingkai Ma 4 , Huijun Yang 4 , Ling Zhang 1 , Hongyan Zhu 1 , Guang-yin Xu 1, 3 , Ge-ping Wu 1, 4 and C. Cao 3 1 Center of Translational Medicine, The First People Hospital of Zhangjiagang City, Soochow University, Suzhou, China 2 Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China 3 Institute of Neuroscience, Soochow University, Suzhou, China 4 Department of Otolaryngology, The First People Hospital of Zhangjiagang City, Soochow University, Suzhou, China * These authors have contributed equally to this work Correspondence to: Ge-ping Wu, email: gordon-wu@qq.com C. Cao, email: caocong@suda.edu.cn Guang-yin Xu, email: guangyinxu@suda.edu.cn Keywords: TBX2, nasopharyngeal cancer, invasion, proliferation, siRNA Received: December 06, 2016 Accepted: March 12, 2017 Published: April 13, 2017 ABSTRACT TBX2 is a member of the T box transcription factor family. Its expression and potential biological functions in nasopharyngeal cancer (NPC) cells are studied here. We showed that TBX2 mRNA and protein expression was significantly elevated in multiple human NPC tissues, as compared with that in adjacent normal tissues. Knockdown of TBX2 by targeted-siRNA significantly inhibited proliferation and invasion of NPC cells (CNE-1 and HONE-1 lines). Meanwhile, TBX2 knockdown also induced G1-phase cell cycle arrest. At the molecular level, we discovered that expressions of several tumor suppressor genes, including p21, p27, phosphatase with tensin homology (PTEN) and E-Cadherin , were increased dramatically after TBX2 knockdown in above NPC cells. Collectively, our results imply that TBX2 over-expression promotes NPC cell proliferation and invasion, possibly via silencing several key tumor suppressor genes.

Aiming at the high failure rate of gearbox-main components of wind turbine and the limitation of single diagnosis method, this paper proposes a fault diagnosis method based on the generalized set of the fuzzy set-the vague set, which combines the vague set and the fault tree. It is introduced into the fault tree model. The triangular Vague set defined on [0], [1] is used to describe the normal, failure and abnormal behavior of bottom events. Based on the fault tree model of the vague set, the qualitative and quantitative analysis of system faults is made. The vague fuzzy operator is used to calculate the importance of each bottom event and judge the weak links of the system. Finally, a wind power gearbox fault example is simulated. The simulation results show that the proposed method is more flexible and practical than the fuzzy fault tree model.

Background Alpha-Tocopherol (α-TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of α-TCP in treating allergic rhinitis remains unclear. Objective In this study we examined the inhibitory function of α-TCP in a mouse model of allergic rhinitis. Methods Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot. Results Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by α-TCP in mast cells. Conclusions Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of α-TCP.

Cognitive impairment is one of the common non-motor symptoms in Parkinson's disease (PD). The hippocampus is a critical structure for learning and memory processes. The abnormal synaptic plasticity in the hippocampus is suggested to be associated with cognitive dysfunction in PD. Voltage gated sodium channels (VGSCs) are key molecules involved in synaptic transmission in the nervous system. Here, the expression patterns of VGSC subtypes Nav1.1, Nav1.3, Nav1.6 in the hippocampus of 6-hydroxydopamine (6-OHDA) lesioned rats were investigated at different time points after 6-OHDA injection. The results showed that the expression of Nav1.1 was remarkably increased in reactive astrocytes at 28days, whereas was sharply reduced at 49days after 6-OHDA injection. However, the expression of Nav1.6 was not different from the control hippocampus at 28days, but was abundantly increased in neurons of the contralateral and ipsilateral hippocampus at 49days after 6-OHDA injection. Moreover, Nav1.3, a subtype predominantly expressed at embryonic stage, was scatteredly re-expressed in neurons of the CA area in the contralateral and ipsilateral hippocampus at 49days after 6-OHDA injection. Furthermore, spatial learning and memory in 6-OHDA lesioned rats were effectively improved by acute treatment with a VGSCs blocker, phenytoin. These findings suggested that VGSCs may play an important role in the genesis of cognitive deficits in PD.

Arterial stiffness indices measured by pulse wave velocity and pulse wave analysis have been widely studied in different populations. Only a few small studies have been reported regarding these two measurement methods. Therefore, the aim of our study was to compare the arterial stiffness indices measured by pulse wave velocity and pulse wave analysis in a randomly selected Chinese population.A total of 4285 subjects were recruited from Gaoyou County, Jiangsu Province, China. There were 2017 (47.1%) participants with hypertension. Pulse wave velocity was assessed by using a VP-1000 Automatic Arteriosclerosis Measurement System. Large artery elasticity and small artery elasticity were measured by pulse wave analysis with an HDI/PulseWave CR-2000 Research CardioVascular Profiling System using the modified Windkessel model.Brachial-ankle pulse wave velocity, large artery elasticity and small artery elasticity were all significantly associated with the Framingham risk score (r = 0.588, -0.387, -0.448; p .001). Brachial-ankle pulse wave velocity was correlated with both large artery elasticity (r = -0.486, p.001) and small artery elasticity (r = -0.455, p .001). In the receiver operating characteristic analysis, brachial-ankle pulse wave velocity [0.834, 95% confidence interval (0.821-0.845)] had a significantly larger area under the curve than both large artery elasticity [0.701, (0.684-0.715)] and small artery elasticity [0.696, (0.678-0.709)].Brachial-ankle pulse wave velocity is significantly correlated with both large artery elasticity and small artery elasticity. The brachial-ankle pulse wave velocity measurement has a better predictive value for hypertension than the large artery elasticity and small artery elasticity measurements. What is new? We investigated the associations between brachial-ankle pulse wave velocity, large artery elasticity and small artery elasticity and compared the values of these indices for predicting hypertension for the first time in a randomly selected large population. What is relevant? Brachial-ankle pulse wave velocity was closely associated with large artery elasticity and small artery elasticity. The brachial-ankle pulse wave velocity measurement was a sensitive test for predicting hypertension in the study population when compared to large artery elasticity and small artery elasticity readings.The present study confirms that brachial-ankle pulse wave velocity is significantly correlated with small and large arterial compliance and is a superior method of diagnosing hypertension compared to large artery elasticity and small artery elasticity.

Alport syndrome (AS) is a rare and inherited renal disorder with an autosomal recessive mode of inheritance. AS patients usually manifest with hematuria and progressive renal disorder also occasionally accompanied by hearing loss and ophthalmic disease. Germline variants in collagen type IV α-4 (COL4A4) gene lead to autosomal recessive Alport syndrome. In the present study, we investigated a Chinese family with Alport syndrome. The index patient is a 24-year-old Chinese woman who has been suffering from proteinuria. Renal biopsy and renal pathology were performed and found focal segmental glomerulosclerosis (FSGS) like lesion in the index patient. The index patient also presented with binocular edema and blurred vision. However, binocular edema dissipated gradually without any further treatment. Unlikely, the index patient was not diagnosed with hearing impairment. Index patient's parents are phenotypically normal. Targeted next generation sequencing and Sanger sequencing was performed. A novel heterozygous single nucleotide insertion, c.4760_4761insC and a previously reported likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC in the COL4A4 gene were identified in the index patient. The novel heterozygous single nucleotide insertion (c.4760_4761insC) leads to a frameshift which eventually results in the formations of a truncated COL4A4 protein. In addition, the other heterozygous likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC, has been already identified with causing AS an autosomal recessive mode of inheritance. Sanger sequencing confirmed that these two variants were inherited in the index patient from her father and mother, respectively. These two variants were not found in 100 normal control individuals. In conclusion, our present finding emphasizes the significance of high throughput targeted next generation sequencing technology for rapid and cost-effective genetic screening which allows us easy and accurate clinical diagnosis of AS patients.

The neuroimaging literature provides compelling evidence for functional dysconnectivity in people with psychosis. However, it is likely that at least some of the observed alterations represent secondary effects of illness chronicity and/or antipsychotic medication. In addition, the extent to which these alterations are specific to psychosis or represent a transdiagnostic feature of psychiatric illness remains unclear. The aim of this study was therefore to examine the diagnostic specificity of functional dysconnectivity in drug-naïve first-episode psychosis (FEP). We used resting-state functional magnetic resonance imaging and functional connectivity analysis to estimate network-level connectivity in 50 patients with FEP, 50 patients with major depressive disorder (MDD), 50 patients with post-traumatic stress disorder (PTSD), and 122 healthy controls (HCs). The FEP, MDD, and PTSD groups showed reductions in intranetwork connectivity of the default mode network relative to the HC group (p

BACKGROUND Syncytin-1, a cell membrane-localizing fusogen, is abnormally expressed in several cancers, including endometrial cancer, breast cancer, and leukemia. Although abnormal syncytin-1 expression has been detected in two-thirds of leukemia blood samples, its expression profile in acute leukemia patients has not yet been analyzed. MATERIAL AND METHODS Bone marrow samples from 50 acute myelogenous leukemia (AML) cases and 14 B-cell acute lymphocytic leukemia (B-cell ALL) patients were subjected to flow cytometry to assess leukocyte type distributions and leukocytic syncytin-1 surface expression. RT-PCR was applied to assess leukocytic syncytin-1 mRNA expression. Statistical analysis was applied to compare syncytin-1 expression between AML and B-cell ALL patients across blasts, granulocytes, lymphocytes, and monocytes as well as to determine clinical factors statistically associated with changes in syncytin-1 expression. RESULTS The leukocyte type distributions of the AML and B-cell ALL cohorts highly overlapped, with an observable difference in blast distribution between the 2 cohorts. The AML cohort displayed significantly greater syncytin-1 surface and mRNA expression (p

In this work, we address the problem of tracking multiple acoustic sources by using an array of microphones in reverberant and noisy environments. Generally, the time difference of arrival (TDOA) measurements are obtained by the peak extraction of the Generalized Cross Correlation (GCC) function, and then used to update source states in the framework of target tracking. In adverse environments, due to the possible false alarms, the missed detections and the poor observability resulting from the unfavorable microphone-source geometry, some microphone pairs may fail to provide efficient measurements. To improve the quality of the measurements and the performance of tracking, two adaptive methods are developed to associate TDOAs across microphone pairs to obtain the position estimates which serve as the pseudo-measurements for the following filtering step. One method is based on the robust least squares, which can associate the TDOAs by assigning TDOAs with different weights adaptively and produce better position estimates. Another method is derived from the idea of microphone selection, which aims to select a subset of microphones rather than using all the microphones. Besides, we develop the multiple targets tracking method and utilize the filter states to predict the source-nearby microphone pairs to avoid the brute-force searching. Experimental results demonstrate that, by introducing the adaptive fusion of TDOAs, performance improvements can be made in both the state and the number estimation.

Different varieties and geographical origins of walnut usually lead to different nutritional values, contributing to a big difference in the final price. The conventional analytical techniques have some unavoidable limitations, e.g., chemical analysis is usually time-expensive and labor-intensive. Therefore, this work aims to apply Fourier transform mid-infrared spectroscopy coupled with machine learning algorithms for the rapid and accurate classification of walnut species that originated from ten varieties produced from four provinces. Three types of models were developed by using five machine learning classifiers to (1) differentiate four geographical origins, (2) identify varieties produced from the same origin, and (3) classify all 10 varieties from four origins. Prior to modeling, the wavelet transform algorithm was used to smooth and denoise the spectrum. The results showed that the identification of varieties under the same origin performed the best (i.e., accuracy = 100% for some origins), followed by the classification of four different origins (i.e., accuracy = 96.97%), while the discrimination of all 10 varieties is the least desirable (i.e., accuracy = 87.88%). Our results implicated that using the full spectral range of 700&ndash, 4350 cm&minus, 1 is inferior to using the subsets of the optimal spectral variables for some classifiers. Additionally, it is demonstrated that back propagation neural network (BPNN) delivered the best model performance, while random forests (RF) produced the worst outcome. Hence, this work showed that the authentication and provenance of walnut can be realized effectively based on Fourier transform mid-infrared spectroscopy combined with machine learning algorithms.

Walnut intake is considered a healthy dietary approach worldwide, particularly as a nutritional tool for the management of obesity and cardiometabolic disorders. Among these lines, leptin and adiponectin, as well as glycemic biomarkers, deserve further attention. We aimed to examine the impact of walnut intake on circulation levels of leptin and adiponectin through a systematic review and meta-analysis of randomized clinical trials (RCTs); secondarily, assessing the glycemic profile as well.The literature search was implemented in four following databases: Web of Science, Scopus, PubMed/Medline, and Google Scholar, thus, determining studies that measured the effects of walnut consumption on adiponectin, leptin, and glycemic biomarkers levels from 2004 up to December 2019.Fourteen trials were include in the meta-analysis, with an intervention period ranging from 5 weeks to 12 months.Walnut intake increased leptin (weighted mean difference (WMD): 2.502 ng/mL; 95 % CI: 2.147-2.856, p 0.001) and adiponectin (WMD: 0.440 ng/mL; 95 % CI: 0.323 to 0.557, p 0.001) levels. Pertaining to glycemic biomarkers, neither overall analyses nor sub-analyses corroborated with changes in fasting blood glucose (WMD: 0.500 mg/dL, 95 % CI: -0.596, 1.596, p = 0.371), insulin (WMD: -0.21 mg/dL, 95 % CI: -0.67, 0.24, p = 0.367), and glycated hemoglobin (WMD: 0.004 mg/dL, 95 % CI: -0.041, 0.049, p = 0.870) concentrations.Walnut intake may increase leptin and adiponectin levels but does not improve glycemic biomarkers.

In this paper, we address the multiple sound source localization problem using time differences of arrival (TDOAs) of sound sources to a microphone array. Typically, TDOAs are estimated based on the peak extraction of the generalized crosscorrelation function. In multi-source cases, for any given microphone pair, it is hard to tell the correspondence between the sound sources and the extracted peaks. In this work, we develop a novel localization approach based on data association which combines multiple TDOAs from the same source across different microphone pairs. Firstly, the generalized cross correlation-phase transform (GCC-PHAT) function is evaluated and multiple peaks of the GCC function indicating candidate TDOAs are extracted for each pair of microphones. Next, we employ the multi-dimensional assignment algorithm to associate multiple TDOAs from the same source. Finally, multiple sound source localization is carried out based on the obtained TDOA associations across different microphone pairs. Experimental results show the proposed method achieves superior performance for multiple sound source localization compared to the competing algorithm, especially in noisy environments.

Introduction Studies using voxel-based morphometry report variable and inconsistent abnormalities of gray matter volume (GMV) and white matter volume (WMV) in brains of preterm-born adolescents (PBA). In such circumstances a meta-analysis can help identify the most prominent and consistent abnormalities. Method We identified 9 eligible studies by systematic search of the literature up to October 2017. We used Seed-based d Mapping to analyze GMV and WMV alterations between PBA and healthy controls. Results In the GMV meta-analysis, PBA compared to healthy controls showed: increased GMV in left cuneus cortex, left superior frontal gyrus, and right anterior cingulate cortex; decreased GMV in bilateral inferior temporal gyrus (ITG), left superior frontal gyrus, and right caudate nucleus. In the WMV meta-analysis, PBA showed: increased WMV in right fusiform gyrus and precuneus; decreased WMV in bilateral ITG, and right inferior frontal gyrus. In meta-regression analysis, the percentage of male PBA negatively correlated with decreased GMV of bilateral ITG. Interpretation PBA show widespread GMV and WMV alterations in the default mode network, visual recognition network, and salience network. These changes may be causally relevant to socialization difficulties and cognitive impairments. The meta-regression results perhaps reveal the structural underpinning of the cognition-related sex differences in PBA.

Brachial-ankle pulse wave velocity (baPWV) can be easily measured in an observer-independent way, but lacks robust population-based validation in terms of fatal combined with nonfatal outcomes.To address this issue, we studied 4251 Chinese randomly recruited Gaoyou County (54.1% women; mean age, 52.1).In the whole study population, mean values were 102.4 mmHg for mean arterial pressure (MAP), 51.1 mmHg for pulse pressure, and 14.8 m/s for baPWV. Over 4.4 years (median), 74 participants experienced a fatal or nonfatal cardiovascular event and 44 a stroke. In multivariable-adjusted Cox regression, standardized hazard ratios expressing the risk of a composite cardiovascular endpoint were 1.77 (95% confidence interval, 1.43-2.20), 1.37 (1.14-1.64) and 1.50 (1.26-1.78) for MAP, PP and baPWV, respectively; the corresponding hazard ratios for stroke were 1.82 (1.39-2.38), 1.39 (1.12-1.74) and 1.53 (1.25-1.89). baPWV did not add to the prediction of cardiovascular events or stroke by MAP (hazard ratios for baPWV, 1.25 and 1.27, respectively; P ≥ 0.053) but refined models including PP (hazard ratios, 1.42 and 1.45; P ≤ 0.0033). The optimized baPWV threshold, obtained by maximizing Youden's index (16.7 m/s), increased the integrated discrimination improvement over and beyond MAP (+1.27%; P = 0.021) and PP (+1.37%; P = 0.038) for the cardiovascular outcome, but not stroke, and increased the net reclassification improvement for both endpoints (≥42.2%; P ≤ 0.004).With fatal and nonfatal cardiovascular and cerebrovascular endpoints as outcome, baPWV marginally increases risk stratification over and beyond MAP, but is a better predictor than PP. A threshold of 16.7 m/s might be used in Chinese populations.

Auto-tuning magnet girder is one of the key technolo-gies to be solved for HEPS-TF (Test Facility of High Ener-gy Photon Source). The girder should have high adjusting accuracy, high stability and can be beam-based aligned, to obtain the stability requirements of beam orbit. There are two girders developed, and the tests have been done. The accuracy of girder motion is within 10 microns while the adjusting range is 1 mm and the resolution is better than 1 microns, the natural frequency is higher than 24 Hz., Proceedings of the 9th Int. Particle Accelerator Conf., IPAC2018, Vancouver, BC, Canada

Population-specific brain templates that provide detailed brain information are beneficial to both structural and functional neuroimaging research. However, age-specific MRI templates have not been constructed for Chinese or any Asian developmental populations. This study developed novel T1-weighted average brain and head templates for Chinese children from 7 to 16 years of age in two-year increments using high quality magnetic resonance imaging (MRI) and well-validated image analysis techniques. A total of 138 Chinese children (51 F/87 M) were included in this study. The internally and externally validated registrations show that these Chinese age-specific templates fit Chinese children's MR images significantly better than age-specific templates created from U.S. children, or adult templates based on either Chinese or North American adults. It implies that age-inappropriate (e.g., the Chinese56 template, the US20–24 template) and nationality-inappropriate brain templates (e.g., U.S. children's templates, the US20–24 template) do not provide optimal reference MRIs for processing MR brain images of Chinese pediatric populations. Thus, our age-specific MRI templates are the first of the kind and should be useful in neuroimaging studies with children from Chinese or other Asian populations. These templates can also serve as the foundations for the construction of more comprehensive sets of nationality-specific templates for Asian developmental populations. These templates are available for use in our database.

In the presence of strong noise or reverberation, the acoustic source localization and tracking problem is confronted with severe challenges. One of them is that the maximal peak of the localization function may not be generated by the real source. In this paper, the stochastic region contraction (SRC) is adopted to search for multiple peaks of the localization function rather than the maximal one only, so as to provide sufficient pseudo-measurement information. A mixed distribution model is used to describe the pseudo-measurement likelihood function within the particle filter framework, where the mixing weight is evaluated based on the idea of probability data association (PDA) by incorporating the dynamic information of the sound source. Simulation results demonstrate that the proposed approach can effectively improve the ability of anti-noise and anti-reverberation of the acoustic target tracking system.

This paper addresses the problem of joint detection and estimation fusion when sensor quantized data are correlated in the distributed system. The traditional methods to handle this joint problem tend to treat the detection and estimation tasks separately, which put more emphasis on the detection part but treat the estimation part sub-optimally. In this work, the joint detection and estimation fusion model is described based on the idea of multi-objective optimization, providing attainable flexibility between the detection and estimation performance. There into, the critical joint likelihood function for multi-sensor correlated data is evaluated based on the Copula theory. Simulation results show that the copula-based joint model outperforms the dependency-ignoring model. Further, the proposed approach is superior to the comparative GLRT (Generalized likelihood ratio test) and NP (Neyman-Pearson) in term of the average estimation cost.

Purpose To use diffusion-tensor (DT) imaging and graph theory approaches to explore the brain structural connectome in pediatric posttraumatic stress disorder (PTSD). Materials and Methods This study was approved by the relevant research ethics committee, and all participants' parents or guardians provided informed consent. Twenty-four pediatric patients with PTSD and 23 control subjects exposed to trauma but without PTSD were recruited after the 2008 Sichuan earthquake. The structural connectome was constructed by using DT imaging tractography and thresholding the mean fractional anisotropy of 90 brain regions to yield 90 × 90 partial correlation matrixes. Graph theory analysis was used to examine the group-specific topologic properties, and nonparametric permutation tests were used for group comparisons of topologic metrics. Results Both groups exhibited small-world topology. However, patients with PTSD showed an increase in the characteristic path length (P = .0248) and decreases in local efficiency (P = .0498) and global efficiency (P = .0274). Furthermore, patients with PTSD showed reduced nodal centralities, mainly in the default mode, salience, central executive, and visual regions (P < .05, corrected for false-discovery rate). The Clinician-Administered PTSD Scale score was negatively correlated with the nodal efficiency of the left superior parietal gyrus (r = -0.446, P = .043). Conclusion The structural connectome showed a shift toward "regularization," providing a structural basis for functional alterations of pediatric PTSD. These abnormalities suggest that PTSD can be understood by examining the dysfunction of large-scale spatially distributed neural networks. © RSNA, 2016.

This paper deals with sound source localization and number estimation in indoor environments using a circular microphone array. Multiple sound source localization is achieved by performing single source localization at each selected time-frequency (TF) point of received signals after short-time Fourier transform. A TF point selection method is proposed to reduce the computational time, which depends on a trained SVM with power and power ratio of TF points as its features. Nonparametric Bayesian clustering is applied on the obtained DOA estimates to identify the number of active sources. The algorithm is shown to outperform others through simulations.

The objectives of this study were to establish the direct and indirect effects of the relationship between body weight and body measurements on both sexes of the indigenous Chinese Dagu chicken and to develop a functional model for predicting body weight using different body measurements. The path analysis in female chickens revealed that shank length has the highest direct effect (path coefficient=0.233) on body weight and pelvis width showed higher indirect effect on body weight via shank length. In male chickens, the path analysis showed that body slope length has the highest direct effect (path coefficient=0.120) on the body weight of indigenous Chinese Dagu chickens, while fossil bone length has the highest indirect effect on body weight via body slope length. The equations could serve as a useful practical tool for livestock farmers, researchers and rural development workers for body weight estimation in the field and for selection purposes.