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The widespread use of smartphones implies that intelligent systems must address the negative emotions experienced by a diverse user group when encountering usability difficulties. Therefore, exploring the relationship between users' emotions and operational behaviors is crucial for further enhancing the accessibility of intelligent systems. Touch dynamics, as a method of dynamic touch data monitoring, has already provided many models for emotion recognition, which are beneficial in gaining insight into users' accessibility needs for smartphones and exploring intelligent solutions to design issues. This paper validates this aspect through interviews and experimental studies. The study first conducted an open-ended interview, and then used a touch behavior experiment with emotional labels and a questionnaire to validate the association between accessibility design flaws in intelligent systems and user emotions. The interview results show that middle-aged and older smartphone users have difficulty activating accessibility tools independently. Consequently, this paper establishes a dataset for emotion classification based on touch gesture data, which is used to gain insight into implicit difficulties in the interaction process through negative emotions. From a touch experiment and questionnaire survey of 57 sample users, there is approximately a 78.57% match between the accessibility needs of intelligent systems and users' negative emotions, with interaction fluency and interface cognition being the main reasons for this phenomenon. Therefore, touch dynamics, as a non-invasive method of emotion recognition, can use negative emotional feedback to gain insights into user needs that are difficult to detect by other methods. This has application value for enhancing users' emotional experience and promoting a transformation in interaction design thinking. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox) is an anticancer drug widely used in tumor chemotherapy, but it has the side-effect of cardiotoxicity, which is closely related to mitochondrial damage. Mitochondrial dynamics is a quality control mechanism that usually helps to maintain a healthy mitochondrial pool. Trophoblast stem cell-derived exosomes (TSC-Exos) have been shown to protect cardiomyocytes from DOX-induced cardiotoxicity. To explore whether the cardioprotective role is mediated by the regulation of mitochondrial dynamic mechanism, TSC-Exos were isolated from human trophoblast stem cells by ultracentrifugation and characterized by Western blot and transmission electron microscopy. Cellular experiments of H9c2 cardiomyocytes co-cultured with Dox and TSC-Exos were performed in vitro to determine the levels of reactive oxygen species generation and apoptosis level. An animal model of heart failure was established by intraperitoneal injection of Dox in vivo, therapy mice were received additional intracardiac injection of TSC-Exos, then, the cardiac function, cardiomyocyte apoptosis and mitochondrial fragmentation were ameliorated. Histology assays suggest that Dox caused an increased tendency of mitochondrial fission, which was manifested by a decrease in the average size of mitochondria. By receiving TSC-Exos treatment, this effect was eliminated. In summary, these results suggest that TSC-Exos alleviate DOX-induced cardiotoxicity through antiapoptotic effect and improving mitochondrial fusion with an increase in Mfn2 expression. This study is the first to provide a potential new treatment scheme for the treatment of heart failure from the perspective of the relationship between TSC-Exos and mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Trimethylamine N-oxide (TMAO) has been linked to cardiovascular disease morbidity and mortality. However, the role of TMAO in the development of abdominal aortic aneurysms (AAAs) is not known. This study investigated the association between TMAO and AAA formation. TMAO and saline were added to the drinking water of angiotensin II (AngII)- and calcium chloride (CaCl2)-induced AAA model mice, respectively. After 4 weeks, the effects of TMAO on AAA development were determined by histology and immunohistology of aortic tissue. The in vitro effects of TMAO were also examined in mouse aortic smooth muscle cells (SMCs). The maximal aortic diameter, incidence of AAA, and degree of elastin degradation were significantly increased in TMAO-treated mice. TMAO also increased the accumulation of the senescence markers p21 and p16, as well as of reactive oxygen species (ROS), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9) in vivo and in vitro. TMAO promoted AAA development in mouse AAA models induced by AngII and CaCl2 by a mechanism involving cellular senescence. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy as a promising method for tumor treatment received tremendous attention. However, the problem of low clinical response rate still needs to be solved, especially in the poorly immunogenic tumors. The enhancement of tumor antigens presentation can effectively activate dendritic cells (DCs) and improve the tumor immunotherapy. In this work, TAK-243 as an inhibitor of the ubiquitin activating enzyme (UAE), was fabricated into cationic lipid-assisted nanoparticle (CLANTAK-243). The obtained CLANTAK-243 could act as an effective tumor immunotherapy enhancer to promote the maturation of DCs as well as antigen presentation, which obviously stimulated the T cells activation and proliferation. Such CLANTAK-243 injected intravenously could well trigger immune response to tumor cells in vivo. Importantly, mice treated with CLANTAK-243 could obtain a long immune memory effect to protect themselves from re-challenged tumor cells. Therefore, this work presented an effective immunotherapy strategy for poorly immunogenic tumor. [ABSTRACT FROM AUTHOR]

Purpose: To identify the specific glucose metrics derived from maternal continuous glucose monitoring (CGM) data, which were associated with a higher percentile of offspring birth weight. Methods: In this cohort study, we recruited singleton pregnant women with GDM who underwent CGM for 5–14 days at a mean of 28.8 gestational weeks between Jan 2017 and Nov 2018. Commonly used single summary glucose metrics of glucose exposure (including mean 24-h, daytime, and nighttime glucose level) and variability (including J-index and mean amplitude of glycaemic excursions) were derived from CGM data. A novel comprehensive glucose metric—hours per-day spent in a severe variability glucose mode (HSSV)—was identified using the spectral clustering method, which reflects both glucose level and variability. Multiple linear regression models were used to estimate the associations of sex- and gestational age-adjusted birth weight percentile with CGM parameters. Results: Ninety-seven women comprising 127,279 glucose measurements were included. Each 1-SD increase in maternal nighttime mean glucose level and HSSV was associated with 6.0 (95% CI 0.4, 11.5) and 6.3 (95% CI 0.4, 12.2) percentage points increase in birth weight percentile, respectively. No associations were found between other glucose metrics and birth weight percentile. Conclusion: Nighttime mean glucose level has a comparable effect size to HSSV in association with fetal growth, suggesting that endogenous hyperglycemia might drive the association between maternal hyperglycemia and birth weight. Further studies need to examine the effect of lowering nighttime glucose level and/or HSSV on preventing fetal overgrowth in GDM women. [ABSTRACT FROM AUTHOR]

We study the thermodynamics of spherically symmetric, neutral and non-rotating black holes in conformal (Weyl) gravity. To this end, we apply different methods: (i) the evaluation of the specific heat; (ii) the study of the entropy concavity; (iii) the geometrical approach to thermodynamics known as thermodynamic geometry; (iv) the Poincaré method that relates equilibrium and out-of-equilibrium thermodynamics. We show that the thermodynamic geometry approach can be applied to conformal gravity too, because all the key thermodynamic variables are insensitive to Weyl scaling. The first two methods, (i) and (ii), indicate that the entropy of a de Sitter black hole is always in the interval 2 / 3 ≤ S ≤ 1 , whereas thermodynamic geometry suggests that, at S = 1 , there is a second order phase transition to an Anti de Sitter black hole. On the other hand, we obtain from the Poincaré method (iv) that black holes whose entropy is S < 4 / 3 are stable or in a saddle-point, whereas when S > 4 / 3 they are always unstable, hence there is no definite answer on whether such transition occurs. Since thermodynamics geometry takes the view that the entropy is an extensive quantity, while the Poincaré method does not require extensiveness, it is valuable to present here the analysis based on both approaches, and so we do. [ABSTRACT FROM AUTHOR]

Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an 'adaptor' while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models. Current strategies to boost anti-tumor immune response include the use of immune checkpoint inhibitors and bispecific T cell-engaging antibodies. Here the authors describe a versatile antibody immobilization nanoplatform that can be used to deliver different combinations of immunotherapeutics, showing therapeutic superiority in pre-clinical models. [ABSTRACT FROM AUTHOR]

Objectives: To determine the role of angiogenic factor with G-patch and FHA domain 1 (AGGF1) in inflammatory response of human dental pulp cells (DPCs) and the underneath mechanism and to explore its role in angiogenesis. Materials and methods: The expression of AGGF-1 in human healthy and inflammatory pulp tissues was detected by immunohistochemistry. RT-qPCR and Western blot were used to evaluate the expression of AGGF1 in DPCs stimulated by lipopolysaccharide (LPS). After AGGF1 was knocked down, the expression of LPS-induced inflammatory cytokines in DPCs was quantified by RT-qPCR and ELISA. Immunofluorescence and Western blot were used to assess the activation of NF-κB signaling. Inflammatory cytokines were detected by RT-qPCR and ELISA in DPCs pretreated with NF-κB pathway inhibitors before LPS stimulation, and then the effect of AGGF1 on angiogenesis was also evaluated. Results: AGGF1 expression increased in inflammatory dental pulp tissues. In DPCs stimulated by LPS, AGGF1 was upregulated in a dose-dependent manner (P < 0.05). In AGGF1 knockdown cells, the expression of IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1/CCL-2) increased by LPS stimulation (P < 0.001). Nuclear translocation of p65 was promoted, and the addition of NF-κB inhibitors inhibited the expression of inflammatory factors. Meanwhile, knockdown of AGGF1 inhibited vascularization. Conclusions: AGGF1 inhibited the synthesis of inflammatory cytokines through NF-κB signaling pathway and promoted the angiogenesis of DPCs. Clinical relevance: This study might shed light in the treatment of pulpitis and regeneration of dental pulp tissues; however, more clinical trials are required to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Birth weight is a strong determinant of infant short- and long-term health outcomes. Family socioeconomic position (SEP) is usually positively associated with birth weight. Whether this association extends to abnormal birth weight or there exists potential mediator is unclear. Methods: We analyzed data from 14,984 mother-infant dyads from the Born in Guangzhou Cohort Study. We used multivariable logistic regression to assess the associations of a composite family SEP score quartile with macrosomia and low birth weight (LBW), and examined the potential mediation effect of maternal pre-pregnancy body mass index (BMI) using causal mediation analysis. Results: The prevalence of macrosomia and LBW was 2.62% (n = 392) and 4.26% (n = 638). Higher family SEP was associated with a higher risk of macrosomia (OR 1.30, 95% CI 0.93–1.82; OR 1.53, 95% CI 1.11–2.11; and OR 1.59, 95% CI 1.15–2.20 for the 2nd, 3rd, and 4th SEP quartile respectively) and a lower risk of LBW (OR 0.69, 95% CI 0.55–0.86; OR 0.76, 95% CI 0.61–0.94; and OR 0.61, 95% CI 0.48–0.77 for the 2nd, 3rd, and 4th SEP quartile respectively), compared to the 1st SEP quartile. We found that pre-pregnancy BMI did not mediate the associations of SEP with macrosomia and LBW. Conclusions: Socioeconomic disparities in fetal macrosomia and LBW exist in Southern China. Whether the results can be applied to other populations should be further investigated. [ABSTRACT FROM AUTHOR]

Convincing evidence indicates that the existence of cancer stem cells (CSCs) within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimination of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanoparticles DTXLNPsiRNA for simultaneous encapsulation of the conventional chemotherapeutic agentdocetaxel (DTXL) and small interfering RNA (siRNA) targeting BMI-1 (siBMI-1). We confirmed that nanoparticles DTXLNPsiBMI-1 effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DTXLNPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DTXLNPsiBMI-1; consequently, the stemness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic killing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor. [ABSTRACT FROM AUTHOR]

The ecological concept of Plant Functional Types (PFTs), which refers to the assemblage of plants with certain functional traits, has been introduced for the study of plant responses to the environment change and human disturbance. Taking the alpine meadow community in the Zoigê Plateau as a study case, this paper classified PFTs in terms of plant nutrition traits. The sequential results are as follows. (1) The main herbages in the Zoigê Plateau included 16 species in 5 families. Among the five families, Cyperaceae vegetation accounted for 81.37% of herbage area in total, while the remaining 4 families occupied less than 20%. As for the species, Kobresia setchwanensis Hand.-Maizz. was dominant, accounting for 48.74% of the total area; while the remaining 51.26% was comprised of Polygonum viviparum L., Anaphalis fiavescens Hand.-Mazz., Stipa aliena Keng and other species. (2) By using the Principal Component Analysis (PCA), the assessment of herbages nutrition was carried out based on the comprehensive multi-index evaluation model. Polygonum viviparum L. had the highest nutritional value score (1.43), and Stipa aliena Keng had the lowest (-1.40). Nutritional value of herbage species had a significantly positive correlation with altitude ( P<0.01) in the Zoigê Plateau. (3) Based on the nutritional values, herbages in the Zoigê Plateau could be grouped into 3 nutrition PFTs (high, medium and low) by using the Natural Breaks (Jenks) method. [ABSTRACT FROM AUTHOR]

The Born in Guangzhou Cohort Study (BIGCS) is a large-scale prospective observational study investigating the role of social, biological and environmental influences on pregnancy and child health and development in an urban setting in southern China. Pregnant women who reside in Guangzhou and who attend Guangzhou Women and Children's Medical Center (GWCMC) for antenatal care in early pregnancy (<20 weeks' gestation) are eligible for inclusion. Study recruitment commenced in February 2012, with an overall participation rate of 76.3%. Study recruitment will continue until December 2018 to achieve the target sample size of 30,000 mother-child pairs. At 30 April 2016, a total of 75,422 questionnaires have been collected, while 14,696 live births have occurred with planned follow-up of cohort children until age 18 years. During the same period a total of 1,053,000 biological samples have been collected from participants, including maternal, paternal and infant blood, cord blood, placenta, umbilical cord, and maternal and infant stool samples. The dataset has been enhanced by record linkage to routine health and administrative records. We plan future record linkage to school enrolment and national examination records. [ABSTRACT FROM AUTHOR]

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups: control group ( n=16), IR group ( n=16), and edaravone-treated IR group ( n=16). An island flap at left lower abdomen (6.0 cm×3.0 cm in size), fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg), once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM). Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion. [ABSTRACT FROM AUTHOR]

In order to evaluate the effect of super chilling (−3 °C) and chilled (3 °C) storage on the quality of rainbow trout fillets, total volatile base nitrogen (TVB-N), drip loss, pH, electric conductivity (EC), total aerobic count (TAC), K and related values, adenosine triphosphate (ATP) and related compounds, color and sensory score were determined and correlation between these indicators were analyzed. According to the comprehensive evaluation of TAC, K value and sensory score, the limit for acceptability of rainbow trout fillets was 5 days at 3 °C and 11 days at −3 °C. Additionally, the correlation coefficients between TVB-N and other freshness indicators (TAC, K value, sensory score) were relatively low. TVB-N may be inadequate for evaluating freshness changes of rainbow trout fillets compared with other indicators. Among the K and related values, H value was a better freshness indicator in rainbow trout fillets during chilled and super chilling storage for its better correlation coefficients with other freshness indicators. Super chilling storage could extend the shelf life of rainbow trout fillets by 6 days compared to chilled storage. [ABSTRACT FROM AUTHOR]

The metabolic pathway of 8-heptadecene in red algae was investigated. The results showed that the amounts of 8-heptadecene in the primitive bangiophycidean red algae Pyropia and Bangia were 30-50 % of the volatile compounds, much higher than that in the green alga Ulva pertusa, the brown alga Sargassum thunbergii and the florideophycidean red alga Gracilaria lemaneiformis. Studies on the metabolism of 8-heptadecene in Pyropia found that its enzymatic system has no significant catalytic activity on palmitic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid. However, the isolated enzymatic solution showed activity in the presence of eicosapentaenoic acid. This activity produced about four times the amount of 8-heptadecene compared with other substrates and the control, indicating the solution had a specific catalytic function for eicosapentaenoic acid. Furthermore, the enzyme solution was strongly inhibited by NaN but not by phenidone and phenanthroline suggesting that the enzyme is structurally related to heme protein. Thus, it is believed that a constant amount of 8-heptadecene is maintained in the primitive red alga Pyropia and the 8-heptadecene is a metabolite of eicosapentaenoic acid and may catalyzed by enzymes including a heme lipoxygenase-like enzyme. [ABSTRACT FROM AUTHOR]

Porphyra yezoensis has a macroscopic foliage gametophyte phase with only a single cell layer, and is ideally suited for the study of the sexual differentiation process, from the vegetative cell to the spermatia. Firstly, we compared variations in the responses of the vegetative and male sectors to desiccation. Later, cell tracking experiments were carried out during the formation of spermatia from vegetative cells. The two sectors showed similar tolerance to desiccation, and the formation of spermatia from vegetative cells was independent of the degree of desiccation. Both light and scanning electron microscopy (SEM) observations of the differentiation process showed that the formation of spermatia could be divided into six phases: the one-cell, two-cell, four-cell, eight-cell, pre-release and spermatia phases. Photomicrographs of Fluorescent Brightener staining showed that the released spermatia had no cell walls. Photosynthetic data showed that there was a significant rise in Y(II) in the four-cell phase, indicating an increase in photosynthetic efficiency of PSII during this phase. We propose that this photosynthetic rise may be substantial and provide the increased energy needed for the formation and release of spermatia in P. yezoensis. [ABSTRACT FROM AUTHOR]

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Recent studies using high-throughput sequencing protocols have uncovered the complexity of mammalian transcription by RNA polymerase II, helping to define several initiation patterns in which transcription start sites (TSSs) cluster in both narrow and broad genomic windows. Here we describe a paired-end sequencing strategy, which enables more robust mapping and characterization of capped transcripts. We used this strategy to explore the transcription initiation landscape in the Drosophila melanogaster embryo. Extending the previous findings in mammals, we found that fly promoters exhibited distinct initiation patterns, which were linked to specific promoter sequence motifs. Furthermore, we identified many 5′ capped transcripts originating from coding exons; our analyses support that they are unlikely the result of alternative TSSs, but rather the product of post-transcriptional modifications. We demonstrated paired-end TSS analysis to be a powerful method to uncover the transcriptional complexity of eukaryotic genomes. [ABSTRACT FROM AUTHOR]

Foliar sprays of calonyctin, a natural plant growth regulator extracted from the leaves of Calonyction aculeatum (L.) House, at a concentration 0.05 activity units, increased the tuber yield of six potato ( Solanum tuberosum L.) cultivars by 7-19% (mean 15%) during 1993 and 1994. Physiological differences between calonyctin-treated and untreated potato plants were usually detected 30-40 days after spraying them with calonyctin. The chlorophyll content of treated potato leaves increased, and the chlorophyll a:b ratio decreased. By 40 days after treatment the root oxidizability and soluble protein contents of different parts of the plants also increased. Their subsequent decline as the plants aged was inhibited by calonyctin. It is concluded that calonyctin delayed the senescence of potato plants and increased tuber growth at later stages of development. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is a well-studied target for the treatment of multiple inflammatory diseases, but how to promote the current therapeutics remains a large challenge. CRISPR/Cas9, as a gene editing tool, allows for direct ablation of NLRP3 at the genomic level. In this study, we screen an optimized cationic lipid-assisted nanoparticle (CLAN) to deliver Cas9 mRNA (mCas9) and guide RNA (gRNA) into macrophages. By using CLAN encapsulating mCas9 and gRNA-targeting NLRP3 (gNLRP3) (CLANmCas9/gNLRP3), we disrupt NLRP3 of macrophages, inhibiting the activation of the NLRP3 inflammasome in response to diverse stimuli. After intravenous injection, CLANmCas9/gNLRP3 mitigates acute inflammation of LPS-induced septic shock and monosodium urate crystal (MSU)-induced peritonitis. In addition, CLANmCas9/gNLRP3 treatment improves insulin sensitivity and reduces adipose inflammation of high-fat-diet (HFD)-induced type 2 diabetes (T2D). Thus, our study provides a promising strategy for treating NLRP3-dependent inflammatory diseases and provides a carrier for delivering CRISPR/Cas9 into macrophages. [ABSTRACT FROM AUTHOR]