Search

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPA p30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPA others). Germline CEBPA p30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPA others carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPA p30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPA others carriers). Among the 27 healthy germline CEBPA -mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations. [Display omitted] • Familial AML with germline CEBPA mutations demonstrates a favorable overall survival. • Germline CEBPA mutations confer a high risk for developing AML. • Report on two new families with multiple cases of AML who carry germline CEBPA mutations. [ABSTRACT FROM AUTHOR]

Generative adversarial networks have been extensively studied in recent years and powered a wide range of applications, ranging from image generation, image-to-image translation, to text-to-image generation, and visual recognition. These methods typically model the mapping from latent space to image with single or multiple generators. However, they have obvious drawbacks: (i) ignoring the multi-modal structure of images, and (ii) lacking model interpretability. Importantly, the existing methods mostly assume one or more generators can cover all image modes even if we do not know the structure of data. Thus, mode dropping and collapse often take place along with GANs training. Despite the importance of exploring the data structure in generation, it has been almost unexplored. In this work, aiming at generating multi-modal images and interpreting model explicitly, we explore the theory on how to integrate GANs with data structure prior, and propose latent Dirichlet allocation based generative adversarial networks (LDAGAN). This framework is extended to combine with a variety of state-of-the-art single-generator GANs and achieves improved performance. Extensive experiments on synthetic and real datasets demonstrate the efficacy of LDAGAN for multi-modal image generation. An implementation of LDAGAN is available at https://github.com/Sumching/LDAGAN. [ABSTRACT FROM AUTHOR]

Abstract A national scale survey was conducted to determine an array of inorganic and organic contaminants in agricultural soils from two cultivation modes (greenhouse vs. open field) in 20 provinces across China. The investigated contaminants include organochlorine pesticides (OCPs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd). The large amounts of agrochemicals used and special cultivation mode in greenhouse caused substantial soil pollution and deterioration of soil quality. Mean concentrations of both OCPs and PAEs in greenhouse soil were approximately 100% higher than those in open field. The pH values were 6.85 ± 1.04 and 7.34 ± 0.84 for greenhouse and open field, respectively (p > 0.05). The soil microbial community was predicted to be affected by pollution in greenhouse through the PICRUSt analysis of 16s rRNA sequences. The 12 variables including various chemicals and soil properties together explained 15% of the observed variation in the community composition. In the studied variables, PAEs and lead were the primary factors affecting microbial diversity in greenhouse soils, while pH had the greatest impact on the microbial community in open field soils. These findings enhanced our understanding of the environmental impact and contamination management of greenhouses worldwide. Graphical abstract Image 1 Highlights • The primary contaminants in greenhouse and open field soil in China were determined. • OCPs and PAEs in greenhouse soil were generally higher than those in open field. • Soil microbial communities changed by the greenhouse cultivation mode. This national scale survey revealed overall pollution status and effect in agricultural soils from greenhouse and open field in 20 provinces across China. [ABSTRACT FROM AUTHOR]

Contamination of organic pollutants in the environment is usually accompanied by heavy metals. However, a little information on the influences of heavy metals on the uptake, translocation and transformation of organic pollutants in plants is available. In this study, ten-day hydroponic exposure was conducted to explore the influence of copper (Cu) on the bioaccumulation and biotransformation of polychlorinated biphenyls (PCBs) in intact young rice ( Oryza sativa L.). Low dose of Cu (≤100 μmol/L) increased the accumulation of CB-61 in rice plants, while excess concentrations of Cu (>100 μmol/L) inhibited uptake and translocation of CB-61. Effect of Cu on the uptake of CB-61 was attributed to the Cu-triggered damage to the roots of rice plants. The presence of a moderate dose of Cu (50 μmol/L) enhanced the formation of hydroxylated polychlorinated biphenyls (OH-PCBs) and methoxylated polychlorinated biphenyls (MeO-PCBs), whereas excess concentrations of Cu (250 μmol/L) inhibited the metabolism of CB-61. The effect of Cu on the interconversion between 4′-OH-CB-61 and 4′-MeO-CB-61 was also concentration dependent: the biotransformation was promoted by a moderate concentration of Cu but inhibited by excess concentrations of Cu. The activities of Cytochrome P450 (CYP450) and S-adenosyl- l -methionine (SAM)-dependent methyltransferase in the roots of rice plants exposed to Cu and CB-61 or its derivatives were consistent with the pattern and trend of the metabolites observed in rice roots. These results could provide valuable insights into the interactions and combined effects of PCBs and heavy metals in plants. [ABSTRACT FROM AUTHOR]

Soil pollution is a global problem in both developed and developing countries. Countries with rapidly developing economies such as China are faced with significant soil pollution problems due to accelerated industrialization and urbanization over the last decades. This paper provides an overview of published scientific data on soil pollution across China with particular focus on organic contamination in agricultural soils. Based on the related peer-reviewed papers published since 2000 (n = 203), we evaluated the priority organic contaminants across China, revealed their spatial and temporal distributions at the national scale, identified their possible sources and fates in soil, assessed their potential environmental risks, and presented the challenges in current remediation technologies regarding the combined organic pollution of agricultural soils. The primary pollutants in Northeast China were polycyclic aromatic hydrocarbons (PAHs) due to intensive fossil fuel combustion. The concentrations of organochlorine pesticides (OCPs) and phthalic acid esters (PAEs) were higher in North and Central China owing to concentrated agricultural activities. The levels of polychlorinated biphenyls (PCBs) were higher in East and South China primarily because of past industrial operations and improper electronic waste processing. The co-existence of organic contaminants was severe in the Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei Region, which are the most populated and industrialized regions in China. Integrated biological-chemical remediation technologies, such as surfactant-enhanced bioremediation, have potential uses in the remediation of soil contaminated by multiple contaminants. This critical review highlighted several future research directions including combined pollution, interfacial interactions, food safety, bioavailability, ecological effects, and integrated remediation methods for combined organic pollution in soil. [ABSTRACT FROM AUTHOR]

The detoxification and degradation of polychlorinated biphenyls (PCBs) have been studied. However, little information is available about the biological mechanisms involved in the metabolism of hydroxylated polychlorinated biphenyls (OH-PCBs) and methoxylated polychlorinated biphenyls (MeO-PCBs) by specific microorganism. In this study, the simultaneous formation of OH-PCB (major metabolite) and MeO-PCB (minor metabolite) was found in Bacillus subtilis after exposure to PCB. Interconversion between MeO-PCB and OH-PCB was also observed and the demethylation ratio of MeO-PCB was higher than the methylation ratio of OH-PCB. The high-throughput RNA-sequencing (RNA-Seq) was conducted to analyze the genes involved in the metabolism processes. The potential metabolism pathways of PCB by Bacillus subtilis were proposed. PCB can be transformed to OH-PCB by Cytochrome P450 encoded by the genes bioI and cypA. The genes ycgJ and ycgI that are related with methyltransferase are potentially involved in the subsequent biotransformation from OH-PCB to MeO-PCB. MeO-PCB was prone to be transformed to OH-PCB by a group of hydrolases. This is the first study considering the mechanism involved in the interconversion between OH-PCBs and MeO-PCBs by microorganism. These findings broaden our insights into the biotransformation mechanism of PCBs in the environment. [ABSTRACT FROM AUTHOR]

The current contamination status of polychlorinated biphenyls (PCBs) was studied in the agricultural soils of the Yangtze River Delta (YRD), one of the largest economic zones in China. The concentrations of PCBs ranged from <0.1 to 130 ng/g dry weight. Higher concentrations of PCBs were observed in the 0–30 cm surface layers relative to the subsurface soils. A distinct spatial distribution was observed with a declining concentration gradient from the northwest to the southeast of the region. The composition of PCBs in the soils was consistent with the Chinese commercial PCB mixtures, but different from the compositions in global background soil. Local sources including large-scale use and disposal of PCB-containing products were the main potential sources to soil. The ecological effects and human health risks associated with combined persistent organic pollutants, including PCBs, organochlorine pesticides (OCPs), phthalate esters (PAEs) and polybrominated diphenyl ethers (PBDEs), were further estimated. The four toxic organic compounds and seven physicochemical parameters together could only explain 12.7% of the variation in microbial community composition, suggesting the soil ecosystem function was not strongly influenced by the combined pollution at low concentrations. However, the potential health risks to residents via multiple pathways were notably higher for PCBs than other chemicals. The potential risks were mainly derived from PCB-126, 81, and 169. [ABSTRACT FROM AUTHOR]

The occurrence and fate of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) have received significant attention. However, there is limited information on the metabolism relationship between OH-pentaBDEs and MeO-pentaBDEs that were frequently detected with relatively high concentrations in the environment. In this study, the biotransformation between OH-BDE-99 and MeO-BDE-99 was investigated in rice, wheat, and soybean plants. All the three plants can metabolize OH-BDE-99 to corresponding homologous methoxylated metabolites, while the transformation from MeO-BDE-99 to OH-BDE-99 could only be found in soybean. The conversion of parent compounds was the highest in soybean, followed by wheat and rice. Transformation products were found mainly in the roots, with few metabolites being translocated to the shoots and solution after exposure. The results of this study provide valuable information for a better understanding of the accumulation and transformation of OH-PBDEs and MeO-PBDEs in different plants. [ABSTRACT FROM AUTHOR]

In Brief: Lactobacillus plantarum GMNL-662 (Lp662) and Lactobacillus plantarum 299v (Lp299v) intervention have a protective effect on osteoporosis caused by colitis induced by DSS, partially through changes in the gut microbiota and a decrease in inflammatory factors. [Display omitted] • This study assessed the effects of probiotics on severe inflammatory bowel disease and osteoporosis. • DSS-induced colitis was used to induce osteoporosis, and short-term (21 days) intervention of probiotics Lactobacillus plantarum GMNL-662 and Lactobacillus plantarum 299v were used to explore its protective effects. • Explore the relationship between intestinal inflammation, gut microbiota, and osteoporosis. • Probiotics' therapeutic potential as an anti-inflammatory treatment to reduce bone loss was suggested. The effects of probiotics Lactobacillus plantarum GMNL-662 (Lp662) and Lactobacillus plantarum 299v (Lp299v) treatment on severe inflammatory bowel disease induced by dextran sodium sulfate was assessed. Male C57BL/6J mice (6 weeks old) were administered 0.9% NaCl, Lp662, or Lp299v by gavage during the entire experiment. After 3 weeks, gut inflammation was associated with bone loss, and compared to the control group, the weight loss caused by colitis in the Lp662 and Lp299v groups decreased (P < 0.001). Pathological sections of the colon showed that probiotics reduced tissue injury, and serum and tissue inflammatory factors decreased significantly (P < 0.05) compared to the control group. Three-dimensional reconstruction images showed that the bone mass in the Lp662 and Lp299v groups was significantly higher than that in the control group. This study highlights the negative impact of chronic gut inflammation on the bone and the therapeutic potential of probiotics as an anti-inflammatory treatment. [ABSTRACT FROM AUTHOR]

Mixture of regressors (MoR) is a widely used regression approach for approximating nonlinear mappings between input and target outputs. However, existing learning procedures for MoR are prone to overfitting when only limited amounts of training data are available. To address this problem, we propose a new mixture regression model, named mixture of grouped regressors (MoGR). It partitions the individual regressors in the model into a set of groups, where the parameters of the regressors within each group are encouraged to take on similar values. As the parameters for each local regressor are learned using all data within a group, they tend to be better conditioned and more robust to noise in the training data. Extensive experiments on real-world head pose and gaze data demonstrate the benefits of our proposed MoGR model. [ABSTRACT FROM AUTHOR]

To reveal the pollution status associated with rapid urbanization and economic growth, extensive areas of agricultural soils (approximately 45,800 km 2 ) in the Yangtze River Delta of China were investigated with respect to selected endocrine disruptor compounds (EDCs), including phthalate esters (PAEs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). The residues of sum of 15 PAEs, sum of 15 OCPs and sum of 13 PBDEs were in the range of 167–9370 ng/g, 1.0–3520 ng/g, and < 1.0–382 ng/g, respectively. The OCPs residuals originated from both historical usage and recent input. Agricultural plastic film was considered to be an important source of PAEs. Discharge from furniture industry was potential major source of PBDEs in this region. The selected pollutants showed quite different spatial distributions within the studied region. It is worth noting that much higher concentrations of the EDCs were found on the borders between Shanghai and the two neighboring provinces, where agriculture and industry developed rapidly in recent years. Contaminants from both agricultural and industrial activities made this area a pollution hotspot, which should arouse more stringent regulation to safeguard the environment and food security. [ABSTRACT FROM AUTHOR]

A fluoropropyl side chain was introduced to the phenyl of the 3,4-dihydroquinazoline scaffold to generate the novel BACE1 PET ligand. Although the in-vitro evaluations of this ligand indicated it possess favorable properties, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand. [Display omitted] The β -site APP-cleaving enzyme 1 (BACE1) plays important roles in the proteolytic processing of amyloid precursor protein, and can be regarded as an important target for the diagnosis and treatment of AD. This study aimed to report the synthesis and evaluation of an 18F-labeled 2-amino-3,4-dihydroquinazoline analog as a potential BACE1 radioligand. A fluoropropyl side chain was introduced to the phenyl of this 3,4-dihydroquinazoline scaffold to generate the radioligand. Our preliminary data indicated that although the 2-amino-3,4-dihydroquinazoline scaffold possessed favorable in-vitro properties as a PET ligand, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand. [ABSTRACT FROM AUTHOR]

Since the invention of Schroeder diffusers, extensive studies have been carried out on the prediction and measurement of diffusion coefficients and correlation scattering coefficients in the far field, providing valuable referring data for public. However, as another important evaluation index, the random-incidence scattering coefficients of Schroeder diffusers, which are popularly used in geometric room acoustic models for accurate predictions, have not yet been systematically studied in the diffusing field. This paper presents an experimental study on the scattering coefficients of two well-known Schroeder diffusers (maximum length sequence (MLS) diffusers and quadratic residue diffusers (QRDs)) in one 1:10 scaled-down reverberation room. The scattering coefficients of these Schroeder diffusers were compared to discover their variation laws as a function of well depth, well width, sequence length and the ratio of the maximum well depth to the wave length. To validate the accuracy and reliability of the scaled-down measurements, the scattering coefficients of six MLS diffusers, as well as their standard deviations, were also measured in a full-size reverberation room. The results measured in this study provide engineers and acousticians with some useful reference data in room acoustics design. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents the results obtained from a student evacuation experiment performed in a four-story building at Tsinghua University. Eighty six young Chinese university students took part in the experiment as evacuees. Five evacuation scenarios were conducted to study occupant route selections and crowd movement under different conditions. The effect of occupant familiarity with the building, occupant initial distribution within the building and exit width on route selection, crowd movement at exits and on stairs are discussed. The evacuations were recorded using digital videos and CCTV cameras in the building. Considerable density, speed and flow rate data at exits and in stairwells is obtained, analyzed and compared with data from SFPE Handbooks. The results have useful implications for understanding the psychological characteristics and crowd movement of people in evacuations. This experimental work is also a preliminary effort toward the goal of building a database on human behavior under emergency situations for the Chinese population. [Copyright &y& Elsevier]

• the graph matching problem is formulated as an Ergodic Markov chain, and the process of matching is addressed to reach the steady-state of the Markov chain. • our algorithm solves the matching problem in O (n 2) space complexity by taking the decomposition of probability transition matrix, and the property leads the algorithm to the matching of super-large graphs (for example, graphs with the number of points over 1000) in limited computing resource and RAM. • our algorithm is evaluated on both the synthetic and the real datasets, and demonstrate that the proposed approach and algorithm is significantly faster and smaller memory than SM, RRWM and FaSM with no loss of accuracy. In theory, graph matching is a combinatorial problem. One state-of-the-art technique in graph matching, called spectral matching, relaxes the matching problem for consistent correspondence into spectral decomposition of the affinity matrix of graphs, but the most variations of spectral based algorithms suffer from their O (n 4) memory requirement. In this paper we propose a probabilistic spectral matching approach, in which the graph matching problem is formulated as an ergodic Markov chain, and the process of matching is addressed to reach the steady-state of the Markov chain. The approach decomposes the probability transition matrix, and solves the matching problem in O (n 2) space complexity using limited computing resource and RAM. This property makes the approach suitable for super-large graphs matching (for example, graphs with the number of points over 1000). We evaluate our algorithm on both the synthetic and the real datasets, and demonstrate that the proposed approach is significantly faster, and consumes smaller memory than SM, RRWM and FaSM with no loss of accuracy. [ABSTRACT FROM AUTHOR]

The method described in ISO 17497-1 standard has been worldwide adopted to measure the random-incident scattering coefficient of irregular surfaces either in a full-size reverberation room or in a scale model. In practical measurements, the sound energy propagation and decay at high frequencies (over 10 kHz) are easily affected by small operating errors and by tiny changes in the measurement conditions. It is difficult to obtain the same accuracy of results in the scale model as that in a full-size reverberation room while maintaining the same setup in both tests as suggested in the standard. This study performed a series of experiments in a 1:10 scale reverberation room to investigate the influence of several practical aspects on measurement accuracy. A maximum length sequence diffuser, with a design frequency of 1700 Hz (full-size value), was used as the specimen. All results obtained in the scaled reverberation room were compared to the reference values measured in a full-size reverberation room. Five factors were studied, which included different recording methods (double-channel and eight-channel), number of source positions (one and four), number of receiver positions (one, two, four and eight), turntable rotation conditions (full-turn or half-turn rotation during T 3 and T 4 measurements), and numbers of averages (24, 36 and 72). The results show that the first three factors above have greater impacts on the measurement accuracy of the scale model experiments than the remaining factors. When the multichannel recording method and four source positions were used in the scaled tests, the measured scattering coefficient values were more reliable, appearing much closer to the reference data over the whole frequency range. Furthermore, applying a half-turn of the turntable (in reference to the measurements of the axisymmetric diffusers) and a 36-impulse coherent average can greatly reduce the test duration without decreasing the measurement accuracy. [ABSTRACT FROM AUTHOR]

Impact events on the Moon have been recognized as modifying the composition of surface materials through processes such as shock metamorphism and mixing with exotic components. Previous studies have indicated that the regolith sampled by the Chinese Chang'E-5 mission was primarily evolved from local mare basalts, likely originating from a single episode of effusive volcanism. The relatively simple and monotonic protolith of the Chang'E-5 regolith presents a unique opportunity to investigate the chemical modifications induced by impact events. In this study, we conducted detailed petrographic and mineralogical analyses on a diverse set of lunar regolith samples, including thirty-three small impact glass particles (39–227 μm), one large agglutinate (∼1.6 mm), and sixteen basaltic clasts (0.1–1.6 mm). Numerical modeling was also conducted to quantitatively assess the melting behavior of basaltic clasts under different impact conditions. Our primary objective was to evaluate the chemical variations of impact glass in relation to lithic clasts. While the majority of homogeneous impact glass spherules and larger basaltic clasts (≥1 mm) exhibit similar bulk compositions (e.g., Al 2 O 3 , CaO and FeO) to the local regolith, we recognize additional effects of impact processes, including impact comminution, impact melting and crystallization, differential volatilization, and potentially selective melting. These processes have modified the texture and geochemistry of lunar regolith components. The chemical signatures of small clasts in the Chang'E-5 regolith indicate that the fine size fractions (e.g., those with diameters of ≤ 300 μm) are predominantly composed of lithic and monomineralic fragments with a substantial proportion being dominated by mesostasis. Melting of these sub-millimeter fractions may lead to the formation of impact glass with chemical compositions deviating from the average local regolith. These results have implications for understanding the compositional evolution of the Chang'E-5 regolith. Notably, our study suggests that impact glasses spherules with different major (e.g., TiO 2 , MgO) and minor (e.g., REEs, Zr, Th and U) element compositions could be derived from the same protolith of local mare basalts, instead of being exclusively attributed to exotic impact ejecta. In this case, small-scale local impacts may have played a crucial role in the impact history of the Chang'E-5 landing site. [ABSTRACT FROM AUTHOR]

Gabbroic and microgabbroic shergottites are intrusive igneous rocks on Mars and exhibit a wide variety of mineralogical and geochemical properties. However, their source reservoirs, magmatic processes and the link to other shergottite subtypes are not well constrained. Northwest Africa (NWA) 13581 is a newly found permafic olivine gabbro, representing a cumulate member in the shergottite group. This sample provides new critical constraints on the characteristics of mantle sources and magmatic evolution of shergottites. The texture and mineral chemistry of NWA 13581 indicate a polybaric crystallization condition, with an increase in oxygen fugacity of approximately 1 log unit after ascent and emplacement. Geochemical studies suggest that the sample is young (150 ± 25 Ma) and may share a similar enriched mantle reservoir (initial ε176Hf i = −18.4, initial ε143Nd i = −7.1) with shergottites like Zagami (basaltic shergottite), NWA 10169 (poikilitic shergottite) and Larkman Nunatak 06319 (olivine-phyric shergottite). In addition, the presence of potassium-rich melt inclusions enclosed in early-formed minerals of NWA 13581 implies a fertile source, probably originating from a metasomatized mantle. The occurrence of similar potassium-rich components in other enriched shergottites may suggest a common process in their mantle reservoir and during crystallization. Overall, NWA 13581 resembles poikilitic shergottites closer than typical gabbroic shergottites in several aspects such as poikilitic texture, mineral chemistry, magmatic evolutionary path, and emplacement conditions. A simplified model is proposed for the formation of NWA 13581 and poikilitic shergottites in the same magma series. Magma mixing and/or assimilation are not the major mechanism that account for their slightly varied mineral modal abundances and quantitative textural characteristics. For samples derived from similar mantle sources, the textural and mineralogical diversities of shergottites are largely related to crystallization at different crustal levels. [ABSTRACT FROM AUTHOR]

By utilizing the complementary information from multiple views, multi-view clustering (MVC) algorithms typically achieve much better clustering performance than conventional single-view methods. Although in this field, great progresses have been made in past few years, most existing multi-view clustering methods still suffer the following shortcomings: (1) most MVC methods are non-convex and thus are easily stuck into suboptimal local minima; (2) the effectiveness of these methods is sensitive to the existence of noises or outliers; and (3) the qualities of different features and views are usually ignored, which can also influence the clustering result. To address these issues, we propose dual self-paced multi-view clustering (DSMVC) in this paper. Specifically, DSMVC takes advantage of self-paced learning to tackle the non-convex issue. By applying a soft-weighting scheme of self-paced learning for instances, the negative impact caused by noises and outliers can be significantly reduced. Moreover, to alleviate the feature and view quality issues, we develop a novel feature selection approach in a self-paced manner and a weighting term for views. Experimental results on real-world data sets demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence. [ABSTRACT FROM AUTHOR]

Abstract Clustering is an important topic in machine learning and data mining. Recently, deep clustering, which learns feature representations for clustering tasks using deep neural networks, has attracted increasing attention for various clustering applications. Deep embedded clustering (DEC) is one of the state-of-the-art deep clustering methods. However, DEC does not make use of prior knowledge to guide the learning process. In this paper, we propose a new scheme of semi-supervised deep embedded clustering (SDEC) to overcome this limitation. Concretely, SDEC learns feature representations that favor the clustering tasks and performs clustering assignments simultaneously. In contrast to DEC, SDEC incorporates pairwise constraints in the feature learning process such that data samples belonging to the same cluster are close to each other and data samples belonging to different clusters are far away from each other in the learned feature space. Extensive experiments on real benchmark data sets validate the effectiveness and robustness of the proposed method. [ABSTRACT FROM AUTHOR]

Background It has been reported increased serum apoM levels seen in the patients suffered from obstructive sleep apnoea and chronic obstructive pulmonary diseases. In the present, we further examine the prevalence of apoM gene SNPs in COPD patients. And a new method base-quenched probe technique is established. Methods In the present study, we first used the Roche 454 GS Junior high-throughput sequencer to analyze 6 COPD samples and 6 control samples, in these samples we found 3 interesting SNPs (rs805264, rs707922 and rs707921) and then we designed primers and probes to establish a simple and quick screening method that is a base-quench probe technique and the genotype was confirmed by melting curves. With this new technique, we further determined 252 COPD samples and 248 normal subjects were applied as controls. Results A total of 19 high-confidence mutations were detected in the Roche 454, 6 mutations among them were not been reported in NCBI, but the mutation frequency was < 20%. Four mutations occurred only in COPD patients, rs751064723 is located in the first exon of transcript 1 and the rest are located in either apoM gene promoter or intron region. The results of melting curve showed that the wild-type and homozygous mutants of rs805264, rs707922 and rs707921 presented melting valley at two different melting temperatures, and the results were consistent with those of DNA sequencing (K = 1, P = 0.000). Conclusions The detection of apoM gene SNPs laid the foundation for the study of the relationship between COPD and apoM, and the base-quenched probe technique is simple, economic and accurate, and it is suitable for a large number of apoM genotyping studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Hypertension induces end-organ damage through inflammation, and autophagy plays a crucial role in the regulation of cellular homeostasis. In the present study, we aimed to define the role of autophagy in the development of inflammation and cardiac injury induced by angiotensin II (Ang II). Methods and Results: Autophagy protein 5 (Atg5) haplodeficiency (Atg5+/−) and age-matched wild-type (WT) C57BL/6J mice were infused with Ang II (1500ng/kg/min) or saline for 7 days. Heart sections were stained with hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical stains. Cytokine and LC3 levels were measured using real-time PCR or western blot analysis. After Ang II infusion, the WT mice exhibited marked macrophage accumulation, cytokine expression, and reactive oxygen species (ROS) production compared with saline-infused controls. However, these effects induced by Ang II infusion were aggravated in Atg5+/− mice. These effects were associated with Atg5-mediated impaired autophagy, accompanied by increased production of ROS and activation of nuclear factor-κB (NF-κB) in macrophages. Finally, increased cardiac inflammation in Atg5 haplodeficient mice was associated with increased cardiac fibrosis. Conclusion: Atg5 deficiency-mediated autophagy increases ROS production and NF-κB activity in macrophages, thereby contributing to cardiac inflammation and injury. Thus, improving autophagy may be a novel therapeutic strategy to ameliorate hypertension-induced inflammation and organ damage. [Copyright &y& Elsevier]

[Display omitted] Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with 68Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of 211At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared 211At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, 211At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, 211At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after 211At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by 211At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Abstract: Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose- and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor. [Copyright &y& Elsevier]

• Measurements were carried out in two multi-purpose performance halls. • Results are compared with existing acoustic energy model predictions. • The best model considers direct sound arrival and onset of reverberant sound decay. • Inaccurate estimation of energy ratios is due to error in estimating late energy. Acoustical measurements were done in two multi-purpose performance halls in the present study. The measured data are compared with predictions from three acoustic energy models in existing literature derived for churches and large reverberant theatres. Results show that the model suitable for the present multi-purpose performance halls is the one which takes into account the time difference between direct sound arrival and onset time of reverberant sound decay. However, unlike the church cases, the time difference appears to have no direct definite relationship with the source-receiver distance alone. A method for the prediction of time difference is then proposed for multi-purpose performance hall application. In addition, the prediction of the late reflected energy is not satisfactory, and this deficiency is the main problem leading to the inaccurate estimation of clarity, definition and centre time in the present study. [ABSTRACT FROM AUTHOR]