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Depression is a major public health problem worldwide and is closely related with systemic inflammatory responses. Additionly, physical activity (PA) is thought to be associated with lower levels of depression and inflammatory markers. This study aimed to elucidate the complex interactions between PA, depression, and inflammatory markers. Based on the National Health and Nutrition Examination Survey (NHANES), various logistic regression were applied to analyze the pairwise correlations among the three. Restrictive cubic splines were constructed to explore the nonlinear relationship between PA and depression. Mediation models were used to identify the mediating role of inflammatory markers. The findings revealed a positive link between depression and inflammatory marker, whereas PA was inversely correlated with both inflammatory marker and depression. Particularly, we noticed the greatest reduction in the risk of depression when the level of PA was between 1200 and 1722 MET-min/week. Besides, we demonstrated that inflammatory markers mediate the potential effects of physical inactivity on depression, ranging from 1.72 % to 6.25 %. In conclusion, PA appear to protect against depression, in which inflammatory markers may play a mediating role. Moreover, we determined the optimal dosage of PA to minimize the likelihood of depression, thereby offering valuable guidance for managing depression. • Physical activity is negatively correlated with both depression and Inflammatory markers • The risk of depression is lowest when the level of physical activity is in the range of 1200 and 1722 MET-min/week • Inflammatory markers mediate the relationship between physical inactivity and depression [ABSTRACT FROM AUTHOR]

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Lactose assimilation is a relatively rare trait in yeasts, and Kluyveromyces yeast species have long served as model organisms for studying lactose metabolism. Meanwhile, the metabolic strategies of most other lactose-assimilating yeasts remain unknown. In this work, we have elucidated the genetic determinants of the superior lactose-growing yeast Candida intermedia. Through genomic and transcriptomic analyses, we identified three interdependent gene clusters responsible for the metabolism of lactose and its hydrolysis product galactose: the conserved LAC cluster (LAC12, LAC4) for lactose uptake and hydrolysis, the conserved GAL cluster (GAL1, GAL7, and GAL10) for galactose catabolism through the Leloir pathway, and a "GALLAC" cluster containing the transcriptional activator gene LAC9, second copies of GAL1 and GAL10, and a XYL1 gene encoding an aldose reductase involved in carbon overflow metabolism. Bioinformatic analysis suggests that the GALLAC cluster is unique to C. intermedia and has evolved through gene duplication and divergence, and deletion mutant phenotyping proved that the cluster is indispensable for C. intermedia's growth on lactose and galactose. We also show that the regulatory network in C. intermedia, governed by Lac9 and Gal1 from the GALLAC cluster, differs significantly from the galactose and lactose regulons in Saccharomyces cerevisiae, Kluyveromyces lactis, and Candida albicans. Moreover, although lactose and galactose metabolism are closely linked in C. intermedia, our results also point to important regulatory differences. IMPORTANCE This study paves the way to a better understanding of lactose and galactose metabolism in the non-conventional yeast C. intermedia. Notably, the unique GALLAC cluster represents a new, interesting example of metabolic network rewiring and likely helps to explain how C. intermedia has evolved into an efficient lactose-assimilating yeast. With the Leloir pathway of budding yeasts acting like a model system for understanding the function, evolution, and regulation of eukaryotic metabolism, this work provides new evolutionary insights into yeast metabolic pathways and regulatory networks. In extension, the results will facilitate future development and use of C. intermedia as a cell-factory for conversion of lactose-rich whey into value-added products. [ABSTRACT FROM AUTHOR]

PHD1 is a member of the prolyl hydroxylase domain protein (PHD1–4) family, which plays a prominent role in the post-translational modification of its target proteins by hydroxylating proline residues. The best-characterized targets of PHD1 are hypoxia-inducible factor α (HIF-1α and HIF-2α), two master regulators of the hypoxia signaling pathway. In this study, we show that zebrafish phd1 positively regulates mavs-mediated antiviral innate immunity. Overexpression of phd1 enhances the cellular antiviral response. Consistently, zebrafish lacking phd1 are more susceptible to spring viremia of carp virus infection. Further assays indicate that phd1 interacts with mavs through the C-terminal transmembrane domain of mavs and promotes mavs aggregation. In addition, zebrafish phd1 attenuates K48-linked polyubiquitination of mavs, leading to stabilization of mavs. However, the enzymatic activity of phd1 is not required for phd1 to activate mavs. In conclusion, this study reveals a novel function of phd1 in the regulation of antiviral innate immunity. IMPORTANCE PHD1 is a key regulator of the hypoxia signaling pathway, but its role in antiviral innate immunity is largely unknown. In this study, we found that zebrafish phd1 enhances cellular antiviral responses in a hydroxylation-independent manner. Phd1 interacts with mavs through the C-terminal transmembrane domain of mavs and promotes mavs aggregation. In addition, phd1 attenuates K48-linked polyubiquitination of mavs, leading to stabilization of mavs. Zebrafish lacking phd1 are more susceptible to spring viremia of carp virus infection. These findings reveal a novel role for phd1 in the regulation of mavs-mediated antiviral innate immunity. [ABSTRACT FROM AUTHOR]

The matching of remote sensing images is a critical and necessary procedure that directly impacts the correctness and accuracy of underwater topography, change detection, digital elevation model (DEM) generation, and object detection. The texture of images becomes weaker with increasing water depth, and this results in matching-extraction failure. To address this issue, a novel method, homography-based motion statistics with an epipolar constraint (HMSEC), is proposed to improve the number, reliability, and robustness of matching points for weak-textured seafloor images. In the matching process of HMSEC, a large number of reliable matching points can be identified from the preliminary matching points based on the motion smoothness assumption and motion statistics. Homography and epipolar geometry are also used to estimate the scale and rotation influences of each matching point in image pairs. The results show that the matching-point numbers for the seafloor and land regions can be significantly improved. In this study, we evaluated this method for the areas of Zhaoshu Island, Ganquan Island, and Lingyang Reef and compared the results to those of the grid-based motion statistics (GMS) method. The increment of matching points reached 2672, 2767, and 1346, respectively. In addition, the seafloor matching points had a wider distribution and reached greater water depths of −11.66, −14.06, and −9.61 m. These results indicate that the proposed method could significantly improve the number and reliability of matching points for seafloor images. [ABSTRACT FROM AUTHOR]

Human liver-derived metabolically competent HepaRG cells have been successfully employed in both two-dimensional (2D) and 3D spheroid formats for performing the comet assay and micronucleus (MN) assay. In the present study, we have investigated expanding the genotoxicity endpoints evaluated in HepaRG cells by detecting mutagenesis using two error-corrected next generation sequencing (ecNGS) technologies, Duplex Sequencing (DS) and High-Fidelity (HiFi) Sequencing. Both HepaRG 2D cells and 3D spheroids were exposed for 72 h to N-nitrosodimethylamine (NDMA), followed by an additional incubation for the fixation of induced mutations. NDMA-induced DNA damage, chromosomal damage, and mutagenesis were determined using the comet assay, MN assay, and ecNGS, respectively. The 72-h treatment with NDMA resulted in concentration-dependent increases in cytotoxicity, DNA damage, MN formation, and mutation frequency in both 2D and 3D cultures, with greater responses observed in the 3D spheroids compared to 2D cells. The mutational spectrum analysis showed that NDMA induced predominantly A:T → G:C transitions, along with a lower frequency of G:C → A:T transitions, and exhibited a different trinucleotide signature relative to the negative control. These results demonstrate that the HepaRG 2D cells and 3D spheroid models can be used for mutagenesis assessment using both DS and HiFi Sequencing, with the caveat that severe cytotoxic concentrations should be avoided when conducting DS. With further validation, the HepaRG 2D/3D system may become a powerful human-based metabolically competent platform for genotoxicity testing. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ), a derivative of chloroquine (CQ), is an antimalarial and antirheumatic drug. Since there is limited data available on the genotoxicity of HCQ, in the current study, we used a battery of in vitro assays to systematically examine the genotoxicity of HCQ in human lymphoblastoid TK6 cells. We first showed that HCQ is not mutagenic in TK6 cells up to 80 μM with or without exogenous metabolic activation. Subsequently, we found that short-term (3–4 h) HCQ treatment did not cause DNA strand breakage as measured by the comet assay and the phosphorylation of histone H2A.X (γH2A.X), and did not induce chromosomal damage as determined by the micronucleus (MN) assay. However, after 24-h treatment, both CQ and HCQ induced comparable and weak DNA damage and MN formation in TK6 cells; upregulated p53 and p53-mediated DNA damage responsive genes; and triggered apoptosis and mitochondrial damage that may partially contribute to the observed MN formation. Using a benchmark dose (BMD) modeling analysis, the lower 95% confidence limit of BMD 50 values (BMDL 50) for MN induction in TK6 cells were about 19.7 μM for CQ and 16.3 μM for HCQ. These results provide additional information for quantitative genotoxic risk assessment of these drugs. ● Hydroxychloroquine induces weak genotoxicity in human TK6 cells after 24-h treatments. ● Hydroxychloroquine is not mutagenic in TK6 cells up to 80 µM after 4-h treatments. ● Hydroxychloroquine upregulates p53 and p53-mediated DNA damage responsive genes. ● The BMDL 50 value for the micronucleus data is about 16.3 μM for hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Heterogeneity exists in populations, and people may benefit differently from the same treatments or services. Correctly identifying subgroups corresponding to outcomes such as treatment response plays an important role in data‐based decision making. As few discussions exist on subgroup analysis with measurement error, we propose a new estimation method to consider these two components simultaneously under the linear regression model. First, we develop an objective function based on unbiased estimating equations with two repeated measurements and a concave penalty on pairwise differences between coefficients. The proposed method can identify subgroups and estimate coefficients simultaneously when considering measurement error. Second, we derive an algorithm based on the alternating direction method of multipliers algorithm and demonstrate its convergence. Third, we prove that the proposed estimators are consistent and asymptotically normal. The performance and asymptotic properties of the proposed method are evaluated through simulation studies. Finally, we apply our method to data from the Lifestyle Education for Activity and Nutrition study and identify two subgroups, of which one has a significant treatment effect. [ABSTRACT FROM AUTHOR]

This paper presents a low‐profile and broadband pattern diversity microstrip antenna with quasiperiodic radiating patches fed by two slots. The thickness of the whole design is only 0.044λ0 (λ0 is the free‐space wavelength of the center frequency), showing great potential in applications. The broadband property is realized by efficiently exciting TM10 mode and antiphase TM20 mode and forming two resonant frequencies in the target band. The antenna can generate a broadside or difference pattern by switching the input port of the broadband 180° hybrid coupling feed network. The measured results show that the coincident impedance bandwidth of the antenna working in the two pattern modes is 20.5% (3.20–3.93 GHz), and the maximum gain values are 6.85 dBi for the directional pattern and 5.80 dBi for the difference pattern. [ABSTRACT FROM AUTHOR]

In this article, we formulate the standard mixture learning problem as a Markov Decision Process (MDP). We theoretically show that the objective value of the MDP is equivalent to the log-likelihood of the observed data with a slightly different parameter space constrained by the policy. Different from some classic mixture learning methods such as Expectation–Maximization (EM) algorithm, the proposed reinforced algorithm requires no distribution assumptions and can handle the non-convex clustered data by constructing a model-free reward to evaluate the mixture assignment based on the spectral graph theory and Linear Discriminant Analysis (LDA). Extensive experiments on both synthetic and real examples demonstrate that the proposed method is comparable with the EM algorithm when the Gaussian mixture assumption is satisfied, and significantly outperforms it and other clustering methods in most scenarios when the model is misspecified. A Python implementation of our proposed method is available at https://github.com/leyuanheart/Reinforced-Mixture-Learning. [ABSTRACT FROM AUTHOR]

Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N -nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT). In this follow-up study, we further examined the genotoxicity and mutagenicity of 15 of these NDSRIs in human TK6 cells. Seven EAT-positive NDSRIs, including N -nitroso-nortriptyline, N -nitroso-fluoxetine, N -nitroso-desmethyl-diphenhydramine, N -nitroso-duloxetine, N -nitroso-lorcaserin, N -nitroso-varenicline, and N -nitroso-sertraline, induced concentration-dependent increases in micronuclei after bioactivation with hamster liver S9. These NDSRIs were also mutagenic in the TK and HPRT gene mutation assays, consistent with their positive EAT results. In the presence of hamster liver S9, the eight EAT-negative NDSRIs were negative in the micronucleus assay and negative for mutation induction. Using TK6 cells endogenously expressing a single human cytochrome P450 (CYP), we found that CYP2C19, CYP2B6, CYP2A6, and CYP3A4 are key enzymes activating the genotoxicity and mutagenicity of these NDSRIs. Overall, the hamster S9-mediated TK6 cell mutagenicity results agreed with those observed in the EAT, indicating consistency in the mutagenic responses produced by NDSRIs across different testing systems. These data support the use of EAT for hazard identification and safety assessment of NDSRIs. • Ames-positive NDSRIs all induced micronuclei after hamster liver S9 bioactivation. • Ames-positive NDSRIs are also mutagenic in human TK6 cells. • Ames-negative NDSRIs are negative in mammalian cell gene mutation assays. • CYP2C19, 2B6, 2A6, and 3A4 are key enzymes for bioactivation of NDSRIs. [ABSTRACT FROM AUTHOR]

The single-beam bathymetric light detection and ranging (LiDAR) system 1 (SBLS-1), which is equipped with a 532-nm-band laser projector and two concentric-circle receivers for shallow- and deep-water echo signals, is a lightweight and convenient prototype instrument with low energy consumption. In this study, a novel LiDAR bathymetric method is utilized to achieve single-beam and dual-channel bathymetric characteristics, and an adaptive extraction method is proposed based on the cumulative standard deviation of the peak and trough, which is mainly used to extract the signal segment and eliminate system and random noise. To adapt the dual-channel bathymetric mechanism, an automatic channel-selection method was used at various water depths. A minimum half-wavelength Gaussian iterative decomposition is proposed to improve the detection accuracy of the surface- and bottom-water waveform components and ensure bathymetric accuracy and reliability. Based on a comparison between the experimental results and in situ data, it was found that the SBLS-1 obtained a bathymetric accuracy and RMSE of 0.27 m and 0.23 m at the Weifang and Qingdao test fields. This indicates that the SBLS-1 was bathymetrically capable of acquiring a reliable, high-efficiency waveform dataset. Hence, the novel LiDAR bathymetric method can effectively achieve high-accuracy near-shore bathymetry. [ABSTRACT FROM AUTHOR]

Accurate bathymetric and topographical information is crucial for coastal and marine applications. In the past decades, owing to its low cost and high efficiency, satellite-derived bathymetry has been widely used to estimate the depth of shallow water in coastal areas. However, insufficient spectral bands and availability of in situ water depths limit the application of satellite-derived bathymetry. Currently, the investigation about the bathymetric potential of hyperspectral imaging is relatively insufficient based on datasets of the Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2). In this study, Zhuhai-1 hyperspectral images and ICESat-2 datasets were utilized to perform nearshore bathymetry and explore the bathymetric capability by selecting different bands based on classical empirical models (the band ratio model and the linear band model). Furthermore, experimental results achieved at the South China Sea indicate that the combination of blue (2 and 3 band) and green (9 band) bands and the combination of red (10 and 12 band) and near-infrared (29 band) bands are most suitable to achieve nearshore bathymetry. Correspondingly, the highest accuracy of bathymetry reached root mean square error values of 0.98 m and 1.19 m for different band combinations evaluated through bathymetric results of reference water depth. The bathymetric accuracy of Zhuhai-1 image is similar with that of Sentinel-2 when employing the blue and green bands. The combination of red and near-infrared bands has a higher bathymetric accuracy for Zhuhai-1 image than that for Sentinel-2 image. [ABSTRACT FROM AUTHOR]

Background: With the recent certification by World Health Organization that the People's Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People's Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. Methods: We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People's Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. Results: P. vivax parasites from the seven studies of five southern and central provinces in the People's Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10–19 days) or long-incubation (228–371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman's rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. Conclusions: Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings. [ABSTRACT FROM AUTHOR]

Background: With the recent certification by World Health Organization that the People's Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People's Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria.Methods: We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People's Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering.Results: P. vivax parasites from the seven studies of five southern and central provinces in the People's Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10-19 days) or long-incubation (228-371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman's rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax.Conclusions: Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings. [ABSTRACT FROM AUTHOR]

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25–100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. This article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation. • Time-dependent increases in mutation frequency were observed following EMS exposure in human airway epithelial tissue models. • CDM expansion, however, did not occur during the current repeat treatment protocol. • General, respiratory, and genotoxicity endpoints peak immediately after repeat dosing with EMS. • Varying recovery kinetics were observed for changes in multiple endpoints. [ABSTRACT FROM AUTHOR]

The incidence rate of thyroid carcinoma ranks ninth among human malignancies, and it accounts for the most frequent malignancy in endocrine-related tumors. This study aimed to investigate the role of long noncoding RNA (lncRNA) ZFAS1 in the metastasis of papillary thyroid carcinoma (PTC) and the potential molecular mechanisms. Both ZFAS1 and MMP3 were highly expressed in thyroid carcinoma and PTC cell, as measured by the q-PCR and TCGA database. In addition, ZFAS1 induced TPC-1 metastasis through inducing the epithelial–mesenchymal transition (EMT) process. Besides, ZFAS1 knockdown by siRNA induced miR-373-3p expression and reduced MMP3 expression, as quantified by q-PCR and Western blotting. According to the luciferase assay, both ZFAS1 and MMP3 were classified as the direct targets of miR-373-3p. However, MMP3 itself did not affect ZFAS1. Using the online prediction tool, CREB3 was predicted as the transcription factor (TF) of ZFAS1 that contained two binding sites on its promoter region, and CREB3 was positively correlated with ZFAS1 in thyroid carcinoma cohorts. Results from the dual-luciferase assay and ChIP-qPCR indicated that both the two binding sites were essential for the transcription of ZFAS1. In conclusion, CREB3 activated lncRNA ZFAS1 at the transcriptional level to promote PTC metastasis by modulating miR-373-3p/MMP3. [ABSTRACT FROM AUTHOR]

Introduction: The effect of dexamethasone on postoperative pain after thyroid surgery remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexamethasone versus placebo on postoperative pain after thyroid surgery. Methods: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of dexamethasone versus placebo on postoperative pain after thyroid surgery. This meta-analysis is performed using the random-effect model. Results: Eight RCTs involving 734 patients are included in the meta-analysis. Overall, compared with control group for thyroid surgery, dexamethasone shows significantly reduced pain scores (SMD = − 0.82; 95% CI − 1.08 to − 0.56; P < 0.00001), number of required analgesics (OR = 0.18; 95% CI 0.11–0.31; P < 0.00001), analgesic consumption (SMD = − 0.38; 95% CI − 0.63 to − 0.13; P = 0.003), nausea and vomiting (OR = 0.38; 95% CI 0.17–0.86; P = 0.02), as well as rescue antiemetics (OR = 0.40; 95% CI 0.20–0.79; P = 0.008). Conclusions: Perioperative dexamethasone is effective to reduce the pain, nausea and vomiting after thyroid surgery. [ABSTRACT FROM AUTHOR]

Chen, Y.; Le, Y.; Xie, Z.; Qiu, Z; Zhang, C.; Cao, B., and Fang, S., 2019. The image matching algorithm basing on homographic constraints for marine surveying, mapping and 3D reconstruction. In: Hoang, A.T. and Aqeel Ashraf, M. (eds.), Research, Monitoring, and Engineering of Coastal, Port, and Marine Systems. Journal of Coastal Research, Special Issue No. 97, pp. 184–190. In the marine surveying and mapping, high-accuracy image matching is of crucial importance to improve the surveying and mapping accuracy. For the low texture area, coastal zone, island and reef, the accuracy of the mapping and 3D reconstruction would be impacted by the number of matching points and the matching accuracy, using the conventional matching algorithms basing on the imaging feature, such as scale-invariant feature transform (SIFT), speed-up robust features (SURF) and oriented brief (ORB) et al.. To overcome and reduce the problem, this paper proposes a new image matching algorithm, the homographic constraint SURF algorithm, which combines the homographic constraint condition and SURF algorithm in order to increase the number of the high-accuracy matching points and improve the accuracy of the mapping and 3D reconstruction for the marine surveying and mapping. Through experiments performance, HCSURF can extract the more number of the matching points and obtain the higher matching accuracy for island and reef images, comparing with the SIFT, SURF and ORB algorithms. In addition, the characteristics and application categories of the HCSURF are analyzed and discussed basing on the experimental results. Using the new proposed matching algorithm can improve and ensure the accuracy of the marine surveying, mapping and 3D reconstruction. [ABSTRACT FROM AUTHOR]

We consider reinforcement learning (RL) methods in offline domains without additional online data collection, such as mobile health applications. Most of existing policy optimization algorithms in the computer science literature are developed in online settings where data are easy to collect or simulate. Their generalizations to mobile health applications with a pre-collected offline dataset remain are less explored. The aim of this article is to develop a novel advantage learning framework in order to efficiently use pre-collected data for policy optimization. The proposed method takes an optimal Q-estimator computed by any existing state-of-the-art RL algorithms as input, and outputs a new policy whose value is guaranteed to converge at a faster rate than the policy derived based on the initial Q-estimator. Extensive numerical experiments are conducted to back up our theoretical findings. A Python implementation of our proposed method is available at . for this article are available online. [ABSTRACT FROM AUTHOR]

Epalrestat (EPS), an aldose reductase inhibitor, is widely prescribed tomanage diabetic neuropathy. It is generally believed that EPS is beneficial to diabetic patients because it can protect endothelial cells, Schwann cells, or other neural cells from oxidative stress. However, several clinical studies revealed that EPS therapy led to liver dysfunction, which limited its clinical applications. Currently, the underlying mechanismby which EPS causes liver dysfunction is unknown. This study aimed to investigate themechanismresponsible for EPS-induced liver injury. Inmouse liver, EPS 1) increased oxidative stress, indicated by increased expression ofmanganese superoxide dismutase, Ho-1, and Nqo1, 2) induced inflammation, indicated by infiltration of inflammatory cells, and induced expression of tumor necrosis factor-alpha, CD11b, and CD11c, as well as 3) predisposed to induce fibrosis, evidenced by increased mRNA and protein expression of early profibrotic biomarker genes procollagen I and alpha-smoothmuscle actin, and by increased collagen deposition. In culturedmouse and human hepatoma cells, EPS treatment induced oxidative stress, decreased cell viability, and triggered apoptosis evidenced by increased Caspase-3 cleavage/activation. In addition, EPS increasedmRNA and protein expression of cytoglobin inmouse liver, indicating that EPS activated hepatic stellate cells (HSCs). Furthermore, EPS treatment in cultured human HSCs increased cell viability. In summary, EPS administration induced oxidative stress and inflammation inmouse liver, and stimulated liver fibrogenesis. Therefore, cautions should be exercised during EPS therapy. [ABSTRACT FROM AUTHOR]

Porous hybrid microspheres were fabricated by the synthesized calcium gluconate- g-poly(D,L-lactide) (CG- g-PDLLA) composites. These hybrid microspheres were treated with an alkaline solution for different period of time to control the amount of generated carboxylate groups and remained CG on the surface. The microspheres were then incubated in a supersaturated simulated body fluid (1.5 SBF) solution for different time to investigate their biomimetic mineralization behavior. The depositions were found to have a fine cluster morphology, a similar crystal structure and chemical structure to natural hydroxyapatite, and a medium Ca/P of approximately 1.30. The effect of surface treating time on the structure and mineralization behavior of these microspheres has been discussed in detail. The results indicate that the nucleation and growth of apatite on the surface are influenced by the induced carboxylate groups and the remained CG. The hybrid CG- g-PDLLA microspheres have the potential as a novel alternative in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Propranolol is a widely used β-blocker that can generate a nitrosated derivative, N -nitroso propranolol (NNP). NNP has been reported to be negative in the bacterial reverse mutation test (the Ames test) but genotoxic in other in vitro assays. In the current study, we systematically examined the in vitro mutagenicity and genotoxicity of NNP using several modifications of the Ames test known to affect the mutagenicity of nitrosamines, as well as a battery of genotoxicity tests using human cells. We found that NNP induced concentration-dependent mutations in the Ames test, both in two tester strains that detect base pair substitutions, TA1535 and TA100, as well as in the TA98 frameshift-detector strain. Although positive results were seen with rat liver S9, the hamster liver S9 fraction was more effective in bio-transforming NNP into a reactive mutagen. NNP also induced micronuclei and gene mutations in human lymphoblastoid TK6 cells in the presence of hamster liver S9. Using a panel of TK6 cell lines that each expresses a different human cytochrome P450 (CYP), CYP2C19 was identified as the most active enzyme in the bioactivation of NNP to a genotoxicant among those tested. NNP also induced concentration-dependent DNA strand breakage in metabolically competent 2-dimensional (2D) and 3D cultures of human HepaRG cells. This study indicates that NNP is genotoxic in a variety of bacterial and mammalian systems. Thus, NNP is a mutagenic and genotoxic nitrosamine and a potential human carcinogen. • NNP induced concentration-dependent mutations in the Ames test in TA98, TA100, and TA1535. • NNP induced micronuclei and gene mutations in TK6 cells in the presence of hamster liver S9. • CYP2C19 was identified as the most active enzyme in the bioactivation of NNP. • NNP induced concentration-dependent DNA strand breakage in metabolically competent human HepaRG cells. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs). Methods: Human DCs and cytotoxic T lymphocytes (CTLs) were obtained from human cord blood mononuclear cells by density gradient centrifugation. Cultured DCs were divided into three groups: dexmedetomidine group, dexmedetomidine plus yohimbine (dexmedetomidine inhibitor) group and control group. DCs in the three groups were treated with dexmedetomidine, dexmedetomidine plus yohimbine and culture medium, respectively. After washing, the DCs were co-incubated with cultured CTLs. The maturation degree of DCs was evaluated by detecting (1) the ratios of HLA-DR-, CD86-, and CD80-positive cells (flow cytometry), and (2) expression of IL-12 and IL-23 (PCR and Elisa). The function of DCs was evaluated by detecting the proliferation (MTS assay) and cytotoxicity activity (the Elisa of IFN-γ) of CTLs. In addition, in order to explore the mechanisms of dexmedetomidine modulating DCs, α2-adrenergic receptor and its downstream signals in DCs were also detected. Results: The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (P>0.05). Compared to the control group, the protein levels of IL-12 and IL-23 in the culture medium and the mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the DCs all decreased in dexmedetomidine group (P<0.05). In addition, the proliferation of CTLs and the secretion of IFN-γ also decreased in the dexmedetomidine group, compared with the control group (P<0.05). Moreover, these changes induced by dexmedetomidine in the dexmedetomidine group were reversed by α2-adrenergic receptor inhibitor yohimbine in the dexmedetomidine plus yohimbine group. It was also found the decrease of mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the dexmedetomidine group could be reversed by ERK1/2 or AKT inhibitors. Conclusion: Dexmedetomidine could negatively modulate human immunity by inhibiting the maturation of DCs and then decreasing the proliferation and cytotoxicity activity of CTLs. The α2-adrenergic receptors and its downstream molecules ERK1/2 and AKT are closely involved in the modulation of dexmedetomidine on DCs. [ABSTRACT FROM AUTHOR]

• A rapid, sensitive and reproducible UPLC-MS/MS coupled to ESI analysis based strategy for determining BG pharmacokinetics was established. • The pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats were altered following the co-intravenous administration of PEG400. • The activities of PEG400 on UGT1A8/1A9 using an in vitro culture system of rat liver microsomes were studied for the first time. Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug–excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CL z) of BG in the rat plasma decreased by 101.60% (p < 0.05), whereas the area under the plasma concentration-time curve (AUC) 0-t and AUC 0-inf increased by 144.59% (p < 0.05) and 140.05% (p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-β-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (V max) and Michaelis–Menten constant (K m) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats. [Display omitted] [ABSTRACT FROM AUTHOR]

Continuous wavelet transform is used for vegetation hyperspectral analysis at two scales among four data sets. The relationship between chlorophyll content and wavelet coefficients was built, and the accuracy was compared to the vegetation index emphasis model. Cross validation was carried out between different data sets. The results show that the accuracy of the wavelet coefficients model is higher than the other models at both scales. Several wavelet features were suitable for chlorophyll retrieval from simulated and measured data sets at the same scale. [ABSTRACT FROM AUTHOR]

The quest for effective virtual screening algorithms is hindered by the scarcity of training data, calling for innovative approaches. This study presents the use of experimental electron density (ED) data for improving active compound enrichment in virtual screening, supported by ED's ability to reflect the time-averaged behavior of ligands and solvents in the binding pocket. Experimental ED-based grid matching score (ExptGMS) was developed to score compounds by measuring the degree of matching between their binding conformations and a series of multi-resolution experimental ED grids. The efficiency of ExptGMS was validated using both in silico tests with the Directory of Useful Decoys-Enhanced dataset and wet-lab tests on Covid-19 3CLpro-inhibitors. ExptGMS improved the active compound enrichment in top-ranked molecules by approximately 20%. Furthermore, ExptGMS identified four active inhibitors of 3CLpro, with the most effective showing an IC50 value of 1.9 µM. We also developed an online database containing experimental ED grids for over 17,000 proteins to facilitate the use of ExptGMS for academic users. Virtual screening methods for drug discovery typically rely on static structures and lack efficient incorporation of dynamic information exhibited in experimental electron densities. Here, the authors develop an approach utilizing multi-resolution experimental electron density maps to screen docking poses, with the effectiveness demonstrated in both the improvement of active compound enriching exhibited in the test using DUD-E data set and the identification of four inhibitors of Covid-19 3CLpro with IC50 of up to 1.9 μM. [ABSTRACT FROM AUTHOR]

SSD and YOLOv5 are the one-stage object detector representative algorithms. An improved one-stage object detector based on the YOLOv5 method is proposed in this paper, named Multi-scale Feature Cross-layer Fusion Network (M-FCFN). Firstly, we extract shallow features and deep features from the PANet structure for cross-layer fusion and obtain a feature scale different from 80 × 80, 40 × 40, and 20 × 20 as output. Then, according to the single shot multi-box detector, we propose the different scale features which are obtained by cross-layer fusion for dimension reduction and use it as another output for prediction. Therefore, two completely different feature scales are added as the output. Features of different scales are necessary for detecting objects of different sizes, which can increase the probability of object detection and significantly improve detection accuracy. Finally, aiming at the Autoanchor mechanism proposed by YOLOv5, we propose an EIOU k-means calculation. We have compared the four model structures of S , M , L , and X of YOLOv5 respectively. The problem of missed and false detections for large objects is improved which has better detection results. The experimental results show that our methods achieve 89.1% and 67.8% mAP @0.5 on the PASCAL VOC and MS COCO datasets. Compared with the YOLOv5_S, our methods improve by 4.4% and 1.4% mAP @ [0.5:0.95] on the PASCAL VOC and MS COCO datasets. Compared with the four models of YOLOv5, our methods have better detection accuracy for large objects. It should be more attention that our method on the large-scale mAP @ [0.5:0.95] is 5.4% higher than YOLOv5_S on the MS COCO datasets. [Display omitted] • We proposed Multi-scale Feature Cross-layer Fusion Network (M-FCFN). • Two completely different feature scales are added as the output. • We propose an EIOU k-means Autoanchor calculation. • The problem of missed and false detections for large objects is improved. • Our method on the large-scale mAP @[0.5:0.95] is 5.4% higher than YOLOv5_S. [ABSTRACT FROM AUTHOR]

This paper focuses on designing a distributed medium access control algorithm for fairly sharing network resources among contending stations in an 802.11 wireless network. Because the notion of fairness is not universal and there lacks a rigorous analysis on the relationships among the four types of most popular fairness criteria, we first mathematically prove that there exist certain connections between these types of fairness criteria. We then propose an efficient medium access algorithm that aims at achieving time fairness and throughput enhancement in a fully distributed manner. The core idea of our proposed algorithm lies in that each station needs to select an appropriate contention window size so as to fairly share the channel occupancy time and maximize the throughput under the time fairness constraint. The derivation of the proper contention window size is addressed rigorously. We evaluate the performance of our proposed algorithm through an extensive simulation study, and the evaluation results demonstrate that our proposed algorithm leads to nearly perfect time fairness, high throughput, and low collision overhead. [ABSTRACT FROM AUTHOR]

Background The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. Methods We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. Results The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high ?-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. Conclusions Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. Methods: We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. Results: The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high γ-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. Conclusions: Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the effects of activated hepatic stellate cells (HSCs) and their paracrine secretions, on hepatocellular cancer cell growth and gene expression in vitro and in vivo. Differentially expressed genes in McA-RH7777 hepatocellular carcinoma (HCC) cells following non-contact co-culture with activated stellate cells, were identified by a cDNA microarray. The effect of the co-injection of HCC cells and activated HSCs on tumor size in rats was also investigated. Non-contact co-culture altered the expression of 573 HCC genes by >2-fold of the control levels. Among the six selected genes, ELISA revealed increased protein levels of hepatic growth factor, matrix metalloproteinase- 2 (MMP-2) and -9 (MMP-9). Incubation of HCC cells with medium conditioned by activated HSCs significantly increased the proliferation rate (P<0.001), migration rate and the number of invasive HCC cells (P=0.001). Co-injection of HCC cells and activated HSCs into rats significantly increased the weight of the resulting HCC tumors (P<0.01). The paracrine activity of activated HSCs markedly altered the gene expression profile of HCC cells and affected their growth, migration and invasiveness. The results from the present study indicate that the interaction between the activated HSCs and HCC has an important role in the development of HCC. [ABSTRACT FROM AUTHOR]

It is known that age is an important factor for postoperative cognitive dysfunction (POCD) and the patients with POCD suffer from the impairment of multiple brain regions and multiple brain functions. However currently animal studies of POCD mainly focus on hippocampus region, therefore in this study we performed partial hepatectomy in young adult and aged rats to test the questions (1) whether POCD in animals involves other brain areas besides hippocampus; (2) how age influences POCD of young adult and aged animals. We found that (1) in young adult rats, the memory was not significantly affected (P>0.05) 1d, 3d and 7d after partial hepatectomy, but was significantly impaired (p<0.001) in aged rats 1d and 3d post-surgery; (2) in young adult rats, the surgery did not significantly affect the densities of dendritic spines of neurons at CA1, dentate gyrus (DG) and cingulate cortex (P>0.05, respectively) 1d and 3d post-surgery, but the spine densities at CA1 and DG of aged rats were significant reduced 1d and 3d post-surgery (p<0.001, respectively), however this didn’t happen at cingulate cortex (P>0.05); (3) In young adult rats, surgery didn’t affect the activation of microglia and levels of TNF-α and IL-1β at hippocampus (P>0.05), but significantly activated microglia and increased levels of TNF-α and IL-1β at hippocampus of aged rats (P<0.05). Our data suggest that (1) partial hepatectomy-induced POCD mainly involves hippocampus impairments, and (2) differential loss of neuronal dendritic spines and neuroinflammation at hippocampus are most likely the mechanism for the formation of POCD in aged rats. [ABSTRACT FROM AUTHOR]

Background: Although many studies have shown glycogen synthase kinase-3β(GSK-3β) was associated with type 2 diabetes mellitus(T2DM) and implicated with a wide range of cancers, the role of GSK-3β in hepatocellular carcinoma(HCC) and the correlation among GSK-3β, T2DM and HCC remains unclear. Our objectives were to identify the effect of p-Ser9-GSK-3β on the prognosis of patients with HCC and to learn more about the interaction among T2DM, GSK-3β and the prognosis of HCC. Methods: Firstly we used reverse transcriptase-PCR(RT-PCR) and western blotting to determine the expression levels of GSK-3β and p-Ser9-GSK-3β in human HCC samples. We then used immunohistochemical staining to evaluate the expression pattern of p-Ser9-GSK-3β in 178 patients with HCC after curative partial hepatectomy. Finally we statistically analyzed the association of p-Ser9-GSK-3β and T2DM with the prognosis of patients with HCC. Results: P-Ser9-GSK-3β was over-expressed in tumor tissues compared with their normal counterparts. Correlation and regression analysis indicated that the over-expression of p-Ser9-GSK-3β was significantly associated with T2DM, and the correlation coefficient was 0.259 (P = 0.001). Multivariate analysis showed that the over-expression of p-Ser9-GSK-3β(P<0.001) and T2DM(P = 0.008) were independently associated with poor prognosis of HCC, respectively. Further analysis demonstrated that these two variables are closely related with each other. Conclusion: The over-expression of p-Ser9-GSK-3β and T2DM are strongly correlated with worse surgical outcome of HCC. P-Ser9-GSK-3β may play a significant role in mediating the influence of T2DM on the prognosis of HCC. [ABSTRACT FROM AUTHOR]

The in vitro micronucleus (MN) assay is a component of most test batteries used in assessing potential genotoxicity. Our previous study adapted metabolically competent HepaRG cells to the high-throughput (HT) flow-cytometry-based MN assay for genotoxicity assessment (Guo et al. in J Toxicol Environ Health A 83:702–717, 2020b, https://doi.org/10.1080/15287394.2020.1822972). We also demonstrated that, compared to HepaRG cells grown as two-dimensional (2D) cultures, 3D HepaRG spheroids have increased metabolic capacity and improved sensitivity in detecting DNA damage induced by genotoxicants using the comet assay (Seo et al. in ALTEX 39:583–604, 2022, https://doi.org/10.14573/altex.22011212022). In the present study, we have compared the performance of the HT flow-cytometry-based MN assay in HepaRG spheroids and 2D HepaRG cells by testing 34 compounds, including 19 genotoxicants or carcinogens and 15 compounds that show different genotoxic responses in vitro and in vivo. 2D HepaRG cells and spheroids were exposed to the test compounds for 24 h, followed by an additional 3- or 6-day incubation with human epidermal growth factor to stimulate cell division. The results demonstrated that HepaRG spheroids showed generally higher sensitivity in detecting several indirect-acting genotoxicants (require metabolic activation) compared to 2D cultures, with 7,12-dimethylbenzanthracene and N-nitrosodimethylamine inducing higher % MN formation along with having significantly lower benchmark dose values for MN induction in 3D spheroids. These data suggest that 3D HepaRG spheroids can be adapted to the HT flow-cytometry-based MN assay for genotoxicity testing. Our findings also indicate that integration of the MN and comet assays improved the sensitivity for detecting genotoxicants that require metabolic activation. These results suggest that HepaRG spheroids may contribute to New Approach Methodologies for genotoxicity assessment. [ABSTRACT FROM AUTHOR]

Abstract: Resveratrol is a highly polyphenolic substance which possesses extensive physiological activities. However, its application is limited by light instability and poor aqueous solubility. In this paper, resveratrol nanodispersion with high light stability and water dissolution rate was prepared by a combination of antisolvent precipitation in the presence of nontoxic polymer and spray-drying. The active ingredients of the unprocessed raw resveratrol decreased 80 wt% when exposed to sun light directly, while that of the resveratrol nanodispersion only reduced 14 wt% at the same condition. The resveratrol nanodispersion dissolved completely in less than 45 min, while raw resveratrol didn''t dissolve completely after 120 min. Meanwhile, resveratrol nanodispersion exhibited better antioxidant activity compared to that of raw resveratrol when added in artificial intestinal juice. This study is helpful to promote the application of resveratrol and provides a routine for enhancing stability and water solubility of photosensitive lipophilic materials. [Copyright &y& Elsevier]

Purpose: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. Methods and Materials: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). Results: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 ± 4.74) than in RH10Gy-SnonR (30.6 ± 3.85) cells, and lowest in McA-RH7777 (11.4 ± 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 ± 5.38), RH10Gy-SnonR (22.17 ± 4.26), and McA-RH7777 (8.3 ± 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-α and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. Conclusions: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of metastasis-related cytokines and factors from NPCs after irradiation may be a possible mechanism for the radiation-induced invasiveness and metastatic potential of HCC. [Copyright &y& Elsevier]

Abstract: Phthalocyanine green (CuPcCl) nanoparticles was successfully prepared by anti-solvent recrystallization method and combined with in situ modification to improve the electrophoretic properties and dispersion ability in organic medium. The produced particles were characterized by SEM, FT-IR and ζ-potential test. It was found that the particles exhibited 120nm with spherical shape and narrow size distribution when the modifier was mixture of CTAB and PVP. Sedimentation ratio of the prepared CuPcCl particles in tetrachloroethylene was nearly down to zero within 30 days and the ζ-potential was 26.8mV. In addition, stable TiO2/C2Cl4 dispersion was prepared by coated TiO2 surface with trimethoxyoctylsilane. The sedimentation ratio of the modified TiO2 was nearly 7.6% within 30 days, and the ζ-potential value was −28.9mV. The particle size was about 300nm with spherical morphology. The results demonstrated that green CuPcCl and white TiO2 dispersions were suitable as electronic ink and showed potential value in the application of electrophoretic display. [Copyright &y& Elsevier]

Abstract: Nanosized 1-[(4-methyl-2-nitrophenyl)azo]-2-naphthalenol (C.I. Pigment Red 3) particles were prepared using a facile liquid precipitation method. The morphology and electrical properties of the produced particles were characterized by SEM, ζ-potential and electrophoretic display device. The particles were ∼80 nm in size within a narrow particle size distribution and displayed excellent electrophoretic properties. The structure and geometry of 1-[(4-methyl-2-nitrophenyl)azo]-2-naphthalenol were investigated using density functional theory, for which, calculated results indicated that the compound possessed both trans- and cis- conformers. UV–vis spectroscopy of the two conformers was evaluated using time-dependent density functional theory taking bulk solvent effects into account by means of the polarizable continuum model. Vertical excitation energies and oscillator strengths were determined for the lowest-energy electronic transitions. The calculated results reproduced the experimental data and corroborated the reliability of the structural characterization of the pigment. [Copyright &y& Elsevier]

Abstract: In this work, ultrafine blue pigment copper phthalocyanine (CuPc) complex particles were prepared by anti-solvent precipitation with in situ modification and characterized by SEM, FT-IR and ζ-potential test. Experimental results showed the prepared particles with average size of 600nm displayed significant improvement in stability and electrophoretic mobility. Sedimentation of the prepared particles in the medium was nearly down to zero within 100h and the electronic response time reduced to 1.14s compared to 45.4s of raw materials. Besides, molecular geometry and vibrational spectroscopy of CuPc–DMSO complex were investigated using DFT method at B3LYP (6-31G, Lanl2dz) levels. The solvent effects have been taken into account based on the polarizable continuum model (PCM). The calculated results demonstrated that the IR spectra agreed with the experimental data rather well and introduction of dielectric medium has obvious effect on the molecular geometry of CuPc–DMSO complex. [Copyright &y& Elsevier]

A high performance liquid chromatography-ultraviolet detector-electrospray ionization tandem mass spectrometry (HPLC/UV/ ESI/MSn) method was used for the chromatographic fingerprint analysis of Gardenia jasminoides fruit, Fructus Gardeniae (zhi-zi in Chinese). Thirteen batches of samples collected from 8 provinces were analyzed to standardize the fingerprint of zhi-zi. The thirteen peaks in the fingerprints of all the 13 batches of samples with reasonable height and good resolution were assigned as "characteristic peaks". Seven "characteristic peaks" were identified by comparing their retention time and MS (mass spectrum) with those of the reference substances for the first time. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine software was used to evaluate the similarities among the 13 batches of zhi-zi samples. The results indicated that samples from different origins had similar HPLC fingerprint and the method could be applied for the quality control of zhi-zi. In addition, the fingerprint can he used to analyze the differences of zhi-zi samples with different harvest time and different parts of Gardenia jasminoides including calyx, root, fruit (zhi-zi), leaf and stem. The results revealed that the chemical compounds in some samples picked in November varied significantly from samples in September and October. The content of geniposide in zhi-zi picked in September and October was much higher than that picked in November. Calyx, leaf stem and root of Gardenia jasminoides had similar chemical components that were significantly different from those of zhi-zi. [ABSTRACT FROM AUTHOR]

Abstract: Ag/SiO2 core–shell nanoparticles within the size of 60nm were applied in marine antimicrobial corrosion coatings. TEM and XRD results indicated silver was completely covered by silica and its crystal form was not affected after coated by silica. Effects of Ag/SiO2 nanoparticles in the microbial corrosion of acrylic-coated steel were studied by means of electrochemical noise analysis (ENA). ENA results reveal that 1wt% Ag/SiO2 nanoparticles exhibit better antimicrobial corrosion activity than that of conventional 40wt% Cu2O biocides. Inductively coupled plasmaoptical emission spectrometry (ICP) showed very lower amount of Ag ions leaching from the matrix resin, whereas a higher amount of copper ion leaching from the resin in the same period. It was concluded Ag/SiO2 core–shell nanoparticles could enhance long-term corrosion protection in comparison with the copper biocides. This composite has a strong potential use in environmentally friendly antimicrobial coatings. [Copyright &y& Elsevier]

Abstract: In this paper, the ultrafine ciprofloxacin (CPF) particles were prepared by the reactive precipitation of ciprofloxacin hydrochloride (CPF·HCl) and NaOH aqueous solution with the presence of isopropyl alcohol (IPA) as the anti-solvent. Subsequently, microsized spherical CPF aggregates were generated using the prepared ultrafine particles as building blocks by spray drying method. The effect of the volume ratio of the CPF solution to anti-solvent (IPA) was investigated. The result shows that the ultra-fined particles of ciprofloxacin can be produced under the volume ratio of 1:15. After spray drying, 3—4 µm spherical aggregates with ultrafine primary CPF particles can be obtained and exhibited great improved aerosol performance with fine particle fraction (FPF) up to 60%. [Copyright &y& Elsevier]

Abstract: Nanosized bicalutamide particles have been obtained by anti-solvent precipitation after screened DMSO and EtOH as co-solvents. The produced nanoparticles have been characterized by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffraction (XRD) and a dissolution test. The mean particle size of bicalutamide is about 450nm with a narrow distribution. The results of the dissolution test show that dissolution rate of the produced nanoparticles are higher than that of the raw material. Besides, DFT calculations of the bicalutamide conformers have firstly been presented. It is found that the calculated geometry structure of lower-energy conformer is very similar to the experimental structure existing within the crystal lattice. The solvent effects have been taken into account based on the polarizable continuum model (PCM). The computed results appear that the introduction of dielectric medium has obvious effect on the molecular geometry of bicalutamide. [Copyright &y& Elsevier]

Abstract: Infectious bursal disease virus (IBDV) is a non-enveloped double-stranded RNA virus belonging to the Birnaviridae family. It shows substantial variation in the major antigen region of the viral capsid protein VP2, where a hypervariable region plays a key role in the virulence of IBDV and its epitope. This study identifies several putative recombinants from previously published data to suggest that homologous recombination may naturally occur between different IBDV strains. In addition, a novel very virulence sublineage emerges in the VP2 phylogenic tree, comprising three putative recombination strains isolated in Korea and China, KSH, KK1 and SH-h. The major putative parents of the three mosaics are descended from the vaccine lineage while their hypervariable regions from vvIBDV. These findings also suggest that vaccine coverage may have influence on the evolution and genetic diversity of IBDV, resulting in a novel group with vvIBDV phenotype through recombination with wild IBDV. [Copyright &y& Elsevier]

Abstract: The structure and UV spectra of fenofibrate have been evaluated in gas phase and in solutions using time dependent density functional theory (TDDFT) method at the B3LYP/6-31G(d), B3LYP/6-311G(d,p) and B3LYP/6-311++G(d,p) levels. The solvent effects have been taken into account based on the polarizable continuum model (PCM). The computed results appear that the introduction of dielectric medium has slight effect on the molecular geometry of fenofibrate. There is one allowed excited state presenting the strongest oscillator strength in the UV region, which is associated with the HOMO→LUMO and HOMO-1→LUMO transition both in gas phase and in solutions. The prediction of the λ max in THF, ethanol and DMSO is 285nm, 286nm and 287nm, respectively, which are in a good agreement with experimental data of 284nm, 285nm and 288nm.The results demonstrate that TDDFT-PCM is a useful tool for study of the electronic absorption in solutions. [Copyright &y& Elsevier]

Abstract: The structures and properties of the silica hollow spheres have been studied by experimental and quantum chemical calculations. The structure of the silica hollow spheres was characterized by TEM, BET and XPS. According to the experimental results, a model of porous silica clusters has been proposed to represent the structure of the silica hollow spheres. The geometry of model was optimized by the semi-empirical PM3 method and the density of states for the model was calculated by ab initio methods at the level of 3-21G and 6-31G. Both the influences of model size and the effect of basis set are discussed. It is found that the calculated binding energies of O1s, Si2s and Si2p are in fairly good agreement with the experimental results. The studies indicate that the small cluster model can be used to reasonably analyzed the structure and properties of silica hollow spheres. [Copyright &y& Elsevier]