Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

BACKGROUND: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation. METHODS: In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27). RESULTS: MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; P≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; P=0.024) and LPA(18:1) (lysophosphatidic acid; P=0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (P<0.001 and P=0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; P=0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]). CONCLUSIONS: An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.

Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs.

The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A, MT-1D, MT-2B, SLC30A2, and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations.

Utility of enteral nutrition via percutaneous transhepatic cholangiography drainage catheterization in late-stage malignant obstructive jaundice.

Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.

Effects of Regulating Hippo and Wnt on the Development and Fate Differentiation of Bovine Embryo.

The improvement of in vitro embryo development is a gateway to enhance the output of assisted reproductive technologies. The Wnt and Hippo signaling pathways are crucial for the early development of bovine embryos. This study investigated the development of bovine embryos under the influence of a Hippo signaling agonist (LPA) and a Wnt signaling inhibitor (DKK1). In this current study, embryos produced in vitro were cultured in media supplemented with LPA and DKK1. We comprehensively analyzed the impact of LPA and DKK1 on various developmental parameters of the bovine embryo, such as blastocyst formation, differential cell counts, YAP fluorescence intensity and apoptosis rate. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to elucidate the in vitro embryonic development. Our results revealed that LPA and DKK1 improved the blastocyst developmental potential, total cells, trophectoderm (TE) cells and YAP fluorescence intensity and decreased the apoptosis rate of bovine embryos. A total of 1203 genes exhibited differential expression between the control and LPA/DKK1-treated (LD) groups, with 577 genes upregulated and 626 genes downregulated. KEGG pathway analysis revealed significant enrichment of differentially expressed genes (DEGs) associated with TGF-beta signaling, Wnt signaling, apoptosis, Hippo signaling and other critical developmental pathways. Our study shows the role of LPA and DKK1 in embryonic differentiation and embryo establishment of pregnancy. These findings should be helpful for further unraveling the precise contributions of the Hippo and Wnt pathways in bovine trophoblast formation, thus advancing our comprehension of early bovine embryo development.

Long-range interaction within the chromatin domain determines regulatory patterns in porcine skeletal muscle.

Spatial chromatin structure is crucial for understanding the early growth and development of porcine skeletal muscle. However, its characteristic of 3D architecture and elaborate regulation of gene transcription remains unclear. In this study, ChIA-PET method is used to study the changes of early chromatin three-dimensional structure in skeletal muscle of lean type Yorkshire pig and fat type Meishan pig. Integrating the in situ Hi-C data revealed the 3D architecture and long-range interaction of the porcine muscle. The results showed the CTCF/RNAPII mediated long-range interaction shapes the different chromatin architecture and dominates the unique regulation of enhancers. In addition, the results revealed that key myogenic genes like ssc-mir-1 had a unique enhancer regulation function in myogenesis. Interestingly, the FGF6 gene is of breed-specific regulation, implying the difference between two breeds in skeletal muscle development. Our research thus may provide a clue for the porcine genetic improvement of skeletal muscle.

Synthesis of Silver Nanoparticles from the Polysaccharide of Farfarae Flos and Uncovering Its Anticancer Mechanism Based on the Cell Metabolomic Approach.

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated in vitro. Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells in vitro, lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.

C/EBP-ß contributes to pig endometrial LE receptivity by targeting cell remodeling genes during implantation.

In brief: Transforming the endometrial luminal epithelium (LE) into a receptive state is a requisite event for successful embryo implantation. This study suggests the role of a transcription factor in regulating endometrial LE receptivity. Abstract: The endometrial luminal epithelium (LE) undergoes extensive remodeling during implantation to establish receptivity of the uterus in response to the conceptus signals, such as interleukin 1ß (IL1B). But the mechanisms remain to be fully understood. This study investigated the role of CCAAT/enhancer-binding protein ß (C/EBP-ß) in regulating pig endometrial LE receptivity. Our results showed that C/EBP-ß was expressed and activated only in the endometrial LE in an implantation-dependent manner. In addition, C/EBP-ß was highly activated at the pre-attachment stage compared to the attachment stage, and its activation was correlated with the expression of IL1B-dependent extracellular signal-regulated kinases1/2-p90 ribosomal S6 kinase signaling axis. Subsequent chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that the binding of C/EBP-ß within the promoter was positively associated with the transcription of genes related to cell remodeling. One such gene is matrix metalloproteinase 8 (MMP8), which is responsible for extracellular matrix degradation. The expression of MMP8 was abundant at the pre-attachment stage but dramatically declined at the attachment stage in the endometrial LE. Consistent with C/EBP-ß, the expression and activation of MMP8 were limited to the endometrial LE in an implantation-dependent manner. Using ChIP-qPCR and electrophoresis mobility shift assay approaches, we demonstrated that C/EBP-ß regulated the expression of the MMP8 gene during implantation. Furthermore, we detected that MMP8 and one of its substrates, type II collagen, showed a mutually exclusive expression pattern in pig endometrial LE during implantation. Our findings indicate that C/EBP-ß plays a role in pig endometrial LE receptivity by regulating cell remodeling-related genes, such as MMP8, in response to conceptus signals during implantation.

Uncovering the Effect of Passage Number on HT29 Cell Line Based on the Cell Metabolomic Approach.

The passage number is an important factor when designing the cell line-based experiment. Although HT29 cells were widely used in the laboratory for colorectal cancer studies, the impact of cell passage number on the HT29 cells was still unknown. In this study, phenotypic assay and metabolomic approach were applied to analyze the systemic effects of passage numbers (passage 4, 10, and 16) on the HT29 cells. The results showed that the increased cell passage number affected the cell cycle distribution and also decreased the proliferation and migration ability of HT29 cells. The metabolomic analysis coupled with heatmap and hierarchical cluster analysis showed obvious metabolome difference among the cells with different passage numbers, which was related with 61 differential metabolites. Three metabolic pathways were determined as the key pathways, and arginine participated in two of them. In addition, it was found that arginine supplementation could inhibit the proliferation ability of HT29 cells in vitro, and a synergistic effect existed between arginine and cisplatin. In conclusion, this study not only revealed the influence of passage numbers on the HT29 cell but also provided an important reference that arginine has the potential role to be developed as the cisplatin therapeutic adjuvant.

The RNA surveillance factor UPF1 regulates the migration and adhesion of porcine skeletal muscle satellite cells.

Skeletal muscle satellite cells (SCs) play an important role in the repairment and regeneration of damaged muscle. The activation, proliferation, migration, and differentiation of SCs are essential to the response to muscle injury. Up-frameshift 1 (UPF1) is involved in the regulation of many developmental processes. However, the role of UPF1 and its associated regulatory mechanism in SCs are still unclear. Here, we analyzed changes in the transcriptome of porcine SCs with UPF1 knockdown. The results showed that focal adhesion and actin cytoskeleton processes were regulated by UPF1. We also confirmed experimentally that UPF1 promoted SC migration and adhesion by regulating the expression of F-Actin, Vinculin, and several adhesion-related genes. Furthermore, we found that phosphorylated focal adhesion kinase (p-FAK) was down-regulated by UPF1 knockdown. This study identifies the role of UPF1 in regulating SC migration and adhesion and therefore provides new insight into the regulatory mechanism of UPF1 in the process of repairing damaged muscle.

Investigating the adsorption behavior and quantitative contribution of Pb2+ adsorption mechanisms on biochars by different feedstocks from a fluidized bed pyrolysis system.

The aim of this study was to examine the qualitative and quantitative analysis of Pb2+ adsorption mechanisms performed with biochars derived from rice straw (RSBs), rice husk (RHBs) and saw dust (SDBs) at several pyrolysis temperatures (400-600 °C) in a fluidized bed system. Adsorption isotherms, kinetics, and desorption analysis were determined, and biochars were analyzed by X-ray Photoelectron Spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope with Energy Dispersive Spectrometer (SEM-EDS) and Boehm titration method. The effect of minerals on Pb2+ adsorption, including precipitation and cation exchange, revealed increasing contribution of precipitation from a range of 4.13%-38.83% to a range of 34.08%-79.94% and decreasing effect of cation exchange from a range of 50.17%-69.75% to a range of 9.57%-43.47% with increasing pyrolysis temperature. However, it remained the dominant adsorption mechanism of all biochars (accounted for 69.49-89.52%). Especially, RSBs with quite high maximum adsorption capacity (qm) values (116-127.57 mgg-1) were mainly due to precipitation mechanism of Pb2+ adsorption, which exhibited better adsorption capacities than RHBs (25.15-30.40 mgg-1) and SDBs (21.81-24.05 mgg-1). Only with the fluidized bed shown in this study, 2.00t RSBs could be produced and the corresponding Pb2+ adsorption may reach 255.50kg per year depending on its maximum adsorption capacity under 500 °C pyrolysis temperature. The results suggest that RSBs produced in a fluidized bed reactor is a promising, cost-effective, engineered biochar for application of Pb2+ remediation in aqueous solutions.

Association between muscle strength and depressive symptoms among Chinese female college freshmen: a cross-sectional study.

BACKGROUND: Increased physical activity level is related to lower risk of depressive symptoms, and there is an inverse association between muscle strength and risk of depressive symptoms among the elderly. Although there is evidence of an inverse association between muscle strength and depressive symptoms, the relationship between these variables in a younger population is still unknown. This study aimed to examine the association between handgrip strength, a representative indicator of skeletal muscle strength, and the risk of depressive symptoms among Chinese female college freshmen. METHODS: A cross-sectional study was conducted among 867 participants aged between 16 and 23 years. Handgrip strength was measured with a handheld digital Smedley dynamometer, and handgrip strength relative to body weight (kg/kg) was calculated and was classified into tertiles as follows: low (0.32-0.50), medium (0.51-0.58), and high (0.59-0.94). Depressive symptoms were evaluated using the 20-item Zung self-rating depression scale (SDS), and three cutoff points were used to indicate different depression levels. RESULTS: We found that 10.7% of participants were classified as having severe depressive symptoms using an SDS score of 50 as the cutoff point. After adjusting for potential confounders, the adjusted odds ratios and 95% confidence intervals (CIs) for moderate-to-severe depressive symptoms across tertiles of the relative handgrip strength were 1.00 (reference) for tertile 1, 0.614 (0.353, 1.069) for tertile 2, and 0.537 (0.292, 0.988) for tertile 3 (P for trend = 0.041). The significant associations remained when other cutoff points (SDS scores: 48 or 45) were used. Interactions between handgrip strength and potential confounders for depressive symptoms in the final models were not significant. CONCLUSIONS: Our findings indicate that handgrip strength is inversely and independently related to the risk of depressive symptoms among Chinese female college freshmen. The present findings can help develop an effective intervention strategy against depression. Further intervention studies are needed to explore the mechanisms underlying the effects of handgrip strength on depressive symptoms.

Profiling and characterization of miRNAs associated with intramuscular fat content in Yorkshire pigs.

miRNAs are short noncoding RNAs that post-transcriptionally regulate gene expression by binding to complementary regions of the target mRNA. The miRNAs associated with the deposition of intramuscular fat (IMF) content in pigs, which is an important meat quality trait, still remain to be investigated. In this study, the longissimus dorsi muscles (LDMs) from 234 individuals were collected from Yorkshire pigs at 90 kg body weight and the miRNA deep sequencing was conducted by using two tailed groups which were taken five individuals each from high (2.94 ± 0.04%) and low (1.62 ± 0.02%) IMF samples. The results showed that total 268 mature miRNAs were identified, of which 70 were previously known, 162 were conserved among species and 36 were identified specifically in pigs. Moreover, 28 miRNAs involved in adipogenesis were differentially expressed in the two groups, and five out of 16 miRNAs were validated by quantitative PCR (qPCR) using stem loop primers. Our results may serve as a fundamental basis for understanding the roles of miRNA in IMF development in pigs. The miRNAs identified in our study can be utilized for research IMF trait in pig population and will provide further clues to the study of meat quality regulatory mechanisms.

Electronic Tongue Recognition with Feature Specificity Enhancement.

As a kind of intelligent instrument, an electronic tongue (E-tongue) realizes liquid analysis with an electrode-sensor array and certain machine learning methods. The large amplitude pulse voltammetry (LAPV) is a regular E-tongue type that prefers to collect a large amount of response data at a high sampling frequency within a short time. Therefore, a fast and effective feature extraction method is necessary for machine learning methods. Considering the fact that massive common-mode components (high correlated signals) in the sensor-array responses would depress the recognition performance of the machine learning models, we have proposed an alternative feature extraction method named feature specificity enhancement (FSE) for feature specificity enhancement and feature dimension reduction. The proposed FSE method highlights the specificity signals by eliminating the common mode signals on paired sensor responses. Meanwhile, the radial basis function is utilized to project the original features into a nonlinear space. Furthermore, we selected the kernel extreme learning machine (KELM) as the recognition part owing to its fast speed and excellent flexibility. Two datasets from LAPV E-tongues have been adopted for the evaluation of the machine-learning models. One is collected by a designed E-tongue for beverage identification and the other one is a public benchmark. For performance comparison, we introduced several machine-learning models consisting of different combinations of feature extraction and recognition methods. The experimental results show that the proposed FSE coupled with KELM demonstrates obvious superiority to other models in accuracy, time consumption and memory cost. Additionally, low parameter sensitivity of the proposed model has been demonstrated as well.

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia.

Hypoxia is an important biochemical and physiological condition associated with uncontrolled growth of tumor. Measurement of hypoxia in tumor tissue may be useful in characterization of tumor progression and monitoring drug treatment. [18F]FMISO is the most widely employed radiotracer for imaging of hypoxic tissue with positron emission tomography (PET). However, it showed relatively low uptake in hypoxic tissues, which led to low target-to-background contrast in PET images. To overcome these shortcomings, two novel 2-fluoroproprioic acid esters, nitroimidazole derivatives 2-fluoropropionic acid 2-(2-nitro-imidazol-1-yl)-ethyl ester (FNPFT, [19F]5) and 2-fluoropropionic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester (FMNPFT, [19F]8), were prepared and tested. Radiolabeling of [18F]5 and [18F]8 was accomplished in 45 min (radiochemical purity >95%, the decay-corrected radiochemical yield of [18F]5 was 11 ± 2%, and that of [18F]8 was 13 ± 2%, n = 5). In vitro cell uptake studies using EMT-6 tumor cells showed that both radiotracers [18F]5 and [18F]8 displayed significantly higher uptake in hypoxic cells than those under normoxic condition, while 2-[18F]fluoropropionic acid (2-[18F]FPA) displayed no difference. Biodistribution studies in mice bearing EMT-6 tumor showed that [18F]5, [18F]8, and 2-[18F]FPA displayed similar tumor and major organ uptakes. Tumor uptake values for all three agents were higher than those of [18F]FMISO, respectively ( P < 0.05). This is likely due to a rapid in vivo hydrolysis of [18F]5 and [18F]8 to their metabolite, 2-[18F]FPA. Micro PET imaging studies in the same EMT-6 implanted mice tumor model also demonstrated that both [18F]5 and [18F]8 displayed similar tumor uptake comparable to that of 2-[18F]FPA. In conclusion, two new fluorine-18 labeled nitroimidazole derivatives, [18F]5 and [18F]8, showed good tumor uptakes in mice bearing EMT-6 tumor. However, in vivo biodistribution results suggested that they were more likely reflect the predominance of in vivo produced metabolite, 2-[18F]FPA, which may not be related to tumor hypoxic condition.

Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

Active Learning on Dynamic Clustering for Drift Compensation in an Electronic Nose System.

Drift correction is an important concern in Electronic noses (E-nose) for maintaining stable performance during continuous work. A large number of reports have been presented for dealing with E-nose drift through machine-learning approaches in the laboratory. In this study, we aim to counter the drift effect in more challenging situations in which the category information (labels) of the drifted samples is difficult or expensive to obtain. Thus, only a few of the drifted samples can be used for label querying. To solve this problem, we propose an innovative methodology based on Active Learning (AL) that selectively provides sample labels for drift correction. Moreover, we utilize a dynamic clustering process to balance the sample category for label querying. In the experimental section, we set up two E-nose drift scenarios-a long-term and a short-term scenario-to evaluate the performance of the proposed methodology. The results indicate that the proposed methodology is superior to the other state-of-art methods presented. Furthermore, the increasing tendencies of parameter sensitivity and accuracy are analyzed. In addition, the Label Efficiency Index (LEI) is adopted to measure the efficiency and labelling cost of the AL methods. The LEI values indicate that our proposed methodology exhibited better performance than the other presented AL methods in the online drift correction of E-noses.

Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9.

Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.

Gas-Sensor Drift Counteraction with Adaptive Active Learning for an Electronic Nose.

Gas sensors are the key components of an electronic nose (E-nose) in violated odour analysis. Gas-sensor drift is a kind of physical change on a sensor surface once an E-nose works. The perturbation of gas-sensor responses caused by drift would deteriorate the performance of the E-nose system over time. In this study, we intend to explore a suitable approach to deal with the drift effect in an online situation. Considering that the conventional drift calibration is difficult to implement online, we use active learning (AL) to provide reliable labels for online instances. Common AL learning methods tend to select and label instances with low confidence or massive information. Although this action clarifies the ambiguity near the classification boundary, it is inadequate under the influence of gas-sensor drift. We still need the samples away from the classification plane to represent drift variations comprehensively in the entire data space. Thus, a novel drift counteraction method named AL on adaptive confidence rule (AL-ACR) is proposed to deal with online drift data dynamically. By contrast with conventional AL methods selecting instances near the classification boundary of a certain category, AL-ACR collects instances distributed evenly in different categories. This action implements on an adjustable rule according to the outputs of classifiers. Compared with other reference methods, we adopt two drift databases of E-noses to evaluate the performance of the proposed method. The experimental results indicate that the AL-ACR reaches higher accuracy than references on two E-nose databases, respectively. Furthermore, the impact of the labelling number is discussed to show the trend of performance for the AL-type methods. Additionally, we define the labelling efficiency index (LEI) to assess the contribution of certain labelling numerically. According to the results of LEI, we believe AL-ACR can achieve the best effect with the lowest cost among the AL-type methods in this work.

Environmental non-governmental organizations and urban environmental governance: Evidence from China.

Environmental non-governmental organizations (ENGOs) play an increasingly important role in the process of urban environmental governance, especially in some developing countries such as China. However, existing studies pay little attention to such an issue in China. In this paper, we consider 113 cities in China from the pollution information transparency index (PITI) list released by ENGOs as the treatment group and some other cities as the control group, and use the difference-in-differences (DID) model and propensity score matching DID (PSM-DID) model to explore the role of ENGOs in China's urban environmental governance. The results show that ENGOs play a significantly positive and robust role in China's urban environmental governance. Furthermore, using regression analysis for eastern, central, and western China, we find that the influence of ENGOs exists in eastern and central China rather than in western China. In addition, the results of the Placebo test indicate that the effect of ENGOs shows an upward trend since 2008. We suggest that ENGOs' role should be strengthened in China, and governments at various levels should take into account environmental information released by ENGOs and consider appropriate measures to improve local environment quality using the obtained information.

Discovery of a class of diheteroaromatic amines as orally bioavailable CDK1/4/6 inhibitors.

The discovery of a class of diheteroaromatic amines based on LY2835219 as cyclin-dependent kinase (CDK1/4/6) inhibitors was described. The series was found to have much more improved CDK1 inhibition and potent in vitro anti-proliferative effects against cancer cell lines. The synthesis and structure-activity relationship studies of these compounds were reported. One promising compound was selected to evaluate as a novel lead compound after in vitro and in vivo profiling.